Effectiveness of Homeopathy For Clinical Conditions - Evaluation of The Evidence PDF
Effectiveness of Homeopathy For Clinical Conditions - Evaluation of The Evidence PDF
Effectiveness of Homeopathy For Clinical Conditions - Evaluation of The Evidence PDF
Clinical Conditions:
Evaluation of the Evidence
Overview Report
October 2013
EFFECTIVENESS OF HOMEOPATHY FOR CLINICAL CONDITIONS: OVERVIEW REPORT October 2013
Table of Contents
Executive Summary .......................................................................................................... 7
1 Background ................................................................................................................ 9
1.1 The purpose of this overview ............................................................................................................................ 10
2 Objective .................................................................................................................. 12
3 Overview methodology ............................................................................................ 12
3.1 Research question development ....................................................................................................................... 13
4.2 Summary of systematic reviews that broadly examined the effectiveness of homeopathy across a range of
clinical conditions ....................................................................................................................................................... 26
4.10.1 Broca’s aphasia in people who have had a stroke ........................................................................... 119
4.13.2 Lactation in postpartum women who elect not to breastfeed ........................................................ 162
List of Abbreviations
Executive Summary
Introduction
Homeopathy is a 200 year-old form of alternative medicine. The discipline is underpinned by the
principle of similitude (‘like cures like’); meaning substances that cause symptoms in a healthy person
have the ability to treat an ill person with the same symptoms (when administered in homeopathic
potencies). Homeopathy is also based on the belief that molecules in highly diluted substances retain
a ‘memory’ of the original substance. Specifically, homeopathic remedies are repeatedly diluted and
agitated in a process known as ‘potentisation’ or ‘dynamisation’.
Homeopathy is included in numerous publicly funded health care systems around the world. It is
therefore essential that clinical evidence is regularly reviewed and that the outcomes of these
reviews are provided in a format that can (i) facilitate decision-making for policy makers, and (ii)
assist the community in making informed decisions about their healthcare. In Australia, the National
Health and Medical Research Council (NHMRC) has a statutory responsibility to provide advice on
health matters and has identified “claiming benefits for human health not based on evidence” as a
major health issue. There have been conflicting reports on the effectiveness of homeopathy;
therefore, NHMRC decided to review the literature addressing the effectiveness of homeopathy for
any clinical condition.
Objective
The objective of this review is to summarise the evidence from systematic reviews regarding the
effectiveness of homeopathy as a treatment for any clinical condition in humans.
Methodology
The methodology used to conduct the review was based on that described in Chapter 22 of the
Cochrane Handbook of Systematic Reviews of Interventions. Literature searches were performed in
EMBASE.com (EMBASE and Medline databases), the Cochrane Library, PubMed, and PubMed Health
to identify all relevant systematic reviews of controlled clinical trials of homeopathy in humans. From
each included systematic review, data was extracted from the individual studies included in the
review by a single reviewer and checked by a second reviewer. In addition, the quality of each
included systematic review was assessed using the AMSTAR measurement tool by a single reviewer
and checked by a second reviewer. The overall conclusion of the systematic review authors was also
recorded. The evidence for each clinical condition was summarised and evidence statements were
formulated after consultation and agreement with the Homeopathy Working Committee (HWC) of
the NHMRC.
Results
A total of 57 systematic reviews were identified that met the criteria for inclusion within this
Overview Report. The relevant reviews tended to have one of three main objectives (i) to review a
variety of complementary and alternative medicines (CAM), including homeopathy, for the
treatment of a particular clinical condition or specific clinical area, (ii) to review homeopathy for the
treatment of one clinical condition, or (iii) to review homeopathy for the treatment of a variety of
clinical conditions. The reviews examined the evidence for a total of 68 clinical conditions and
included seven clinical conditions for which no relevant primary studies were identified. Of the
remaining 61 clinical conditions, the total number of participants included in the trial(s) was less than
150 for 36 of the clinical conditions examined. The total number of participants included in the
trial(s) was between 150 and 499 for 15 clinical conditions. The evidence base for 10 clinical
conditions collectively comprised 500 or more participants. There were 31 clinical conditions for
which only one Level II or Level III-2 study was identified.
In rating the body of evidence, the overall size, quality and precision of the evidence was considered
and a level of confidence (LOC) was assigned to the body of evidence for each clinical condition.
Overall, there was no condition for which there was a high LOC in the body of evidence. One
condition was associated with a moderate LOC and four conditions were associated with a moderate-
low LOC. Fifty-six clinical conditions were associated with a low or very low LOC (14 conditions with a
low LOC; 11 conditions with a low-very low LOC; 31 conditions with a very low LOC). The remaining
seven clinical conditions could not be assigned a LOC as there were no relevant primary studies
identified.
Discussion
The quality and comprehensiveness of the systematic reviews included in this Overview Report were
limited by the inclusion of many poorly designed, conducted and reported primary studies.
Importantly, most of the primary studies were small in size and likely to be insufficiently powered to
detect a statistically significant outcome. Also, this Overview Report was reliant upon the reporting
within the included systematic reviews, which was not always high quality. In addition, several
systematic reviews did not provide specific conclusions relating to each clinical condition included in
the review.
Conclusion
There is a paucity of good-quality studies of sufficient size that examine the effectiveness of
homeopathy as a treatment for any clinical condition in humans. The available evidence is not
compelling and fails to demonstrate that homeopathy is an effective treatment for any of the
reported clinical conditions in humans.
1 Background
Homeopathy is a form of complementary and alternative medicine (CAM) that is commonly used to
treat or manage a wide variety of clinical conditions. Developed by Samuel Christian Hahnemann in
the late 18th century, homeopathy is founded on two fundamental principles: similitude (‘like cures
like’) and potentisation (or ‘dynamisation’), whereby a substance is repeatedly diluted and agitated
(‘succussion’). The principle of similitude is known as ‘similia similibus curantur’ and is based on the
hypothesis that a substance that causes certain symptom(s) in a healthy person (usually at high
doses) can be used to treat those symptoms in a person who is ill (at small doses). Homeopathic
medicines are prepared by serial dilution in alcohol or distilled water, followed by forceful striking on
an elastic body, called ‘succussion’. Each dilution followed by succussion is assumed to increase the
medicine’s potency due to a transfer of energy, meaning that higher diluted preparations are
considered to be more active. The serial dilution of various animal, plant, mineral or synthetic
substances to create a homeopathic remedy often occurs to a point at which it is highly unlikely that
a single molecule of the original substance remains (Ernst and Barnes, 1998). The principle of
potentisation is based on the belief that even though it is highly diluted, the solvent retains a
‘memory’ of the original substance.
Globally, homeopathy is one of the most extensively used forms of CAM (Linde et al, 1997) and is
included in numerous publicly funded health care systems around the world. In Australia, herbal
products, vitamins, minerals and nutritional supplements, some aromatherapy products and certain
homeopathic products are regulated as complementary medicines under the Therapeutic Goods Act
1989 by the Therapeutic Goods Administration (TGA). Homoeopathic preparations are currently
exempt from inclusion on the Australian Register of Therapeutic Goods (ARTG) prior to supply,
providing they contain ingredients more dilute than a 1,000 fold dilution of a mother tincture, do not
contain substances of human origin or certain animal parts, and do not make therapeutic claims that
refer to serious conditions or diseases.
It is estimated that Australians spent US $7.3 million dollars on homeopathic medicines in 2008
(WHO, 2009). Despite its widespread use, homeopathy remains highly controversial due to a large
discordance between its underlying principles and those of biomedical science (Davidson et al, 2011).
Still, homeopathy is often adopted as a treatment strategy, particularly by patients with difficult-to-
treat conditions who are frustrated with conventional therapeutic options or their side effects.
Given the prevalence of its use, there is a strong incentive for policy makers and consumers to
understand the existing evidence base for homeopathy but consensus across various government
reports and systematic reviews has not been reached. For example, in 2009 the UK House of
Commons Science and Technology Committee released a report entitled Evidence Check 2:
Homeopathy, in which they argued “there has been enough testing of homeopathy and plenty of
evidence showing that it is not efficacious” and surmised that “systematic reviews and meta-analyses
conclusively demonstrate that homeopathic products perform no better than placebo” (House of
Commons Science and Technology Committee, 2009). Overall, the report recommended that the
National Health Service (NHS) stop funding homeopathy. However, the report has been criticised for
inaccurately representing the findings of several key systematic reviews and overstating the findings
of reviews or meta-analyses that found no effect for homeopathy (British Homeopathic Association,
2010).
In contrast to the findings of the UK report, a Swiss Health Technology Assessment (HTA) report in
Homeopathy (published in English in February, 2012) concluded that homeopathy is a “valuable
addition to the conventional medical landscape” (Bornhöft and Matthiessen, 2012). However, recent
reviews of the Swiss report have suggested that it is “scientifically, logically and ethically flawed”,
“misinterprets studies previously exposed as weak” and “attempts to discredit randomised
controlled trials as the gold standard of evidence” (Shaw, 2012).
In view of the inconsistency among published reviews, as well as the fact that neither of the above
reviews addressed homeopathy in the Australian context, the National Health and Medical Research
Council (NHMRC) recognised that an updated systematic review of systematic reviews (an overview)
on this topic was needed to critically appraise and summarise the evidence on homeopathy. As part
of this decision, NHMRC established the Homeopathy Working Committee (HWC), which comprises
experts in evidence-based medicine and CAM. NHMRC contracted Health Technology Analysts Pty
Ltd (the evidence reviewer, trading as Optum) to conduct an overview that would examine the
effectiveness of homeopathy for the specific treatment of any clinical condition in humans, including
treating the clinical side effects of another treatment or intervention. NHMRC is also evaluating and
considering published guidelines, other government reports and evidence submitted to the NHMRC.
This Overview Report provides a comprehensive description of the methods used to assess the
evidence and includes a summary of the findings of the systematic review(s) and an evidence
statement for each clinical condition.
Figure 1 Flow chart outlining the purpose of the Overview Report in the context of the broader project
2 Objective
The objective of this overview is to summarise the evidence from systematic reviews regarding the
effectiveness of homeopathy as a treatment for any clinical condition in humans.
In considering the effectiveness of homeopathy for this review, the HWC determined the following
uses are also within scope (i) homeopathy used to treat the side effects of another
treatment/intervention; and (ii) homeopathy used in conjunction with another
treatment/intervention, where the design of the study does not confound the results (i.e. where the
specific effect of homeopathy can be determined). For example, studies that examined homeopathy
plus other intervention versus other intervention were included. The use of homeopathy as a
preventative/prophylactic intervention was considered out of scope. In addition, the report did not
include studies that exclusively examined safety or homeopathic aggravations, defined as a
temporary worsening of existing symptoms following the administration of a homeopathic remedy
(Grabia and Ernst, 2003); however safety results reported in otherwise included studies were
presented in the report.
3 Overview methodology
Prior to conducting the evidence evaluation of the effectiveness of homeopathy for the treatment of
any clinical condition in humans, a research protocol was developed through active consultation
between the members of the HWC and the evidence review team. This research protocol specified
the methodology to be used in the review and was approved by NHMRC before the review
commenced. The methods used were derived from Chapter 22 of the Cochrane Handbook of
Systematic Reviews of Interventions, which is designed to compile evidence from multiple systematic
reviews into a single document. This overview does not aim to repeat the searches of the systematic
reviews, or repeat the assessments of eligibility or risk of bias conducted by the included systematic
reviews.
This section outlines:
The primary clinical research question used to define the systematic evidence review
The literature search strategies used to identify studies relevant to the primary clinical
research question
The study eligibility criteria used to determine the inclusion or exclusion of studies for this
overview
A description of the quality assessment and critical appraisal process and the data extraction
forms used to capture information from the systematic reviews
A description of the process used to assess the body of evidence relative to the primary
clinical research question, including the development of evidence summaries and evidence
statements
A brief description of how comments from the independent methodological review have
been addressed
The agreed PICO criteria for the primary clinical research question are detailed in Table 1.
Table 1 PICO criteria for the primary clinical research question developed for the overview
For patients with a specific clinical condition, is homeopathy an effective treatment, compared with no
homeopathy/other treatments?
People with any clinical (1) Homeopathy for No homeopathy Any clinical Limits:
condition the treatment of Standard or usual outcome Search period: January 1997-
any clinical care 3 January 2013
condition a
Stratified by: Any other active Adverse events Full length publications only
• Age (adults; children (2) Homeopathy for treatment English only publicationsb
or adolescents) the treatment of
• Indigenous/non- clinical side effects
indigenous of another
treatment or
intervention
(3) Homeopathy
used in conjunction
with another
intervention, where
the specific effects
of homeopathy can
be determined
Stratified by
practitioner
prescribed and self-
prescribed where
applicable
a
Adverse events were only considered if they were included within a systematic review that also considered
effectiveness.
b
Studies were excluded if they were not published in the English language. Non-English publications that otherwise
fulfilled the eligibility criteria were brought to the attention of the HWC, noted and excluded.
identified. Where there was ambiguity about what constitutes a clinical condition, this was clarified
through consultation with the HWC.
To maximise the generalisability and applicability of the review findings, the evidence evaluation
included any clinical condition for which there was at least one systematic review that searched for
prospectively designed and controlled studies conducted in humans.
for the purposes of this review, systematic reviews were eligible if they contained one or more of the
following study types: RCT, pseudo-randomised controlled trial, non-randomised controlled trial or
prospective cohort study. Furthermore, if a systematic review identified no studies for a particular
clinical condition, this information was included in the evidence review.
The literature search strategies used to identify publications relevant to the primary clinical research
question are shown in Table 3. The literature searches were conducted using EMBASE.com (which
searches EMBASE and Medline databases concurrently), the Cochrane Library, PubMed and PubMed
Health. After reviewing the initially retrieved citations, a manual search of the reference lists of
included papers was also performed to identify other potential reviews that may have met the
criteria for inclusion in this overview, but were missed by the initial search strategy.
Table 3 Literature search strategy for the systematic review of systematic reviews
Database # Search terms Citations Total number
retrieved of citations
#3 #1 AND #2 436
Search date:
10 January 2013
Search date:
3 January 2013
Consistent with the PICO criteria for the systematic review (Table 1), the following a priori exclusion
criteria were applied to the citations retrieved through the literature search:
Duplicate citation
Wrong publication type. Studies that were not systematic reviews or meta-analyses were
excluded. Editorials, comments, book chapters, animal studies, correspondence, and news
items were excluded. Studies were also excluded if they were not reported in full (e.g.
research or systematic review protocols, conference proceedings, articles published in
abstract form)
Wrong intervention. Studies that did not investigate the effect of homeopathy were excluded
Wrong outcomes. Studies that did not include outcomes relevant to the primary research
question were excluded
Study not published in the English language
The data were extracted by a single reviewer and checked by a second reviewer. Data extraction was
completed only for systematic reviews that received a ‘yes’ rating for questions 3 and 7 of the
AMSTAR measurement tool (Shea et al, 2007). Systematic reviews that received a ‘yes’ rating in
question 3 but did not identify any included studies and therefore could not have answered yes to
question 7 were also included. Data extraction forms for all included studies are presented in
Appendix A.
appropriate pooling of results was not applicable and the systematic review was given a score out of
10. Similarly, if a systematic review did not identify any primary studies for the clinical condition of
interest the systematic review was given a score out of 5. For the purposes of the evidence
statements, those reviews that identified primary studies were also assigned a quality rating (poor,
medium, good) based on the AMSTAR score. There are no established thresholds for assigning
descriptive quality ratings; however, for the purposes of this Overview Report, a score of 5 or less
was considered ‘poor’, 6-8 ‘medium’ and 9+ was considered a ‘good’ quality systematic review. The
same thresholds were applied regardless of whether the denominator was 10 or 11.
Information on primary outcomes of the primary studies was often not reported in the
systematic reviews
Difficulty in ascertaining if different systematic reviews were reporting on the same outcome
of a primary study
It was unclear from many systematic reviews if the reported sample size of a primary study
was the number of people randomised or the number of people who completed the study.
Thus, different systematic reviews reported different sample sizes for the same primary
study
box in the ‘results as reported in the systematic review’ column was shaded. This approach was
adopted irrespective of the reporting of a p-value (<0.05). For the purposes of this Overview Report,
“effectiveness” was defined as a statistically significant improvement in a clinically relevant outcome.
The clinical significance (or the practical importance) of an outcome was not assessed by the
evidence reviewer.
The quality of the included studies was also not assessed by the evidence reviewer as the primary
studies were not retrieved. The methodological quality of the primary studies that are reported in
the Overview Report are based on the scores assigned by the authors of the systematic reviews. The
majority of systematic reviewers that assessed the quality of the included studies used the Jadad
scoring system to rate quality. Further information about the classification of primary studies is
provided in Appendix C.
Ideally, the evidence reviewer would have focused on a ‘key’ systematic review in each evidence
summary. In some therapeutic areas, this approach is possible due to large evidence bases and
rigorous meta-analyses. However, it was difficult to adopt that approach in this overview, as the
systematic reviews were often of poor methodological quality, or reporting from poorly conducted
trials.
The methodological reviewer provided five key points and numerous specific recommendations that
were intended to improve the transparency of the methods and the interpretation of the findings.
The findings of the methodological review were discussed at a meeting of the HWC on 11 July 2013.
The Overview Report and Appendix A were modified in response to the recommendations of the
methodological reviewer and additional appendixes, Appendix B and Appendix C, were added to the
Overview Report. The evidence statements were also refined to reflect suggestions in the
methodological review.
The methodological reviewer was provided with an updated version of the Overview Report and a
response to their initial comments and concerns. The methodological reviewer then examined the
changes and provided final comments and suggestions that were incorporated into the Overview
Report on 9 September 2013.
The literature search was conducted on 3 January 2013, and not December 2012 as reported
in the research protocol. Consequently, articles published or otherwise made available after
3 January 2013 were not included in the evaluation of the evidence.
Studies that were identified during the systematic review of Level I evidence were not
assessed according to the NHMRC dimensions of evidence as planned in the research
protocol. These dimensions were originally developed for use in assessing primary studies. It
became apparent during the evidence review that they would not be appropriate for
overviews, as study-level data was often incompletely reported in the systematic reviews
(e.g. primary outcomes were often not specified, effect estimates and confidence intervals
were rarely reported).
Appendix A in the protocol (Table 1 in the Overview Report) has been updated. The research
question now reflects the fact that data pertaining to adverse events were included in the
overview if such information was found in a systematic review that also considered
effectiveness. The other changes to the table were not significant in terms of content; the
changes were made in order to facilitate a clearer understanding of the research question
for the reader.
The research protocol stated that “for each condition and outcome a summary of the
identified evidence will be presented. This will include an evidence table with the details of
the evidence and a discussion of the strengths and limitations of the included studies, the
powering of the studies and a description of the totality of the evidence”. Additionally, the
research protocol stated that the results will be presented by outcome.
However, the included systematic reviews presented a wide array of outcomes which were
often reported differently between systematic reviews. This made it difficult to ascertain
whether outcomes that were reported differently between two or more systematic reviews
were, in fact, referring to the same results. Consequently, the evidence summary tables
have been presented according to systematic review and not by outcome. Each primary
study that was identified by each systematic review is listed with the study details, meaning
that some trials are listed numerous times within one evidence table. This change was
necessitated due to incomplete reporting; it was very rare that one systematic review
reported all of the outcomes, results, and patient characteristics of an included study. Thus,
all primary trial data is presented as it was reported in the systematic reviews.
The research protocol stated that “the full quality checklist developed for this project,
including a key to the three quality ratings (good, moderate, poor) is shown in Appendix C
(of the research protocol)”. This key was not provided in Appendix C of the protocol but is
described in Section 3.6.2 of this Overview Report.
The research protocol described a standard sentence format for the development of
evidence statements. However, a different, new framework was developed by the evidence
reviewer in conjunction with the HWC due to the incomplete reporting of the systematic
reviews and the difficulty in ascertaining which results were the primary outcomes. Details
of the new framework are provided in Section 3.6.2 of this Overview Report.
The research protocol stated that a ‘Process Report’ would accompany the Overview Report
and comprise most of the methodology. It was later decided by NHMRC that this
information should be read in conjunction with the evidence evaluation and was thus
integrated into the Overview Report.
In Appendix A of the research protocol, footnote ‘a’ to the table states that “preference will
be given to patient-relevant over surrogate outcomes”. This was subsequently deleted as it
was not applicable to this evidence evaluation.
The quality of each of these 60 systematic reviews was assessed using the AMSTAR measurement
toolkit (Appendix A). Three studies were subsequently excluded as they did not assess the quality of
the included studies (question 7 of the AMSTAR measurement tool) and are listed in Table 5. This
resulted in a final total of 57 systematic reviews that were appraised in this Overview Report, with
full citation details presented in Section 7.1.1. Sources of funding and the declared interests of the
authors in each included review are detailed in the corresponding data extraction form for the study
(Appendix A).
a
Table 5 Citation details for excluded studies that failed to meet ‘essential’ quality criteria
Jorm AF, Christensen H, Griffiths KM, Parslow RA, Rodgers B, Blewitt KA (2004) Effectiveness of complementary and self-
help treatments for anxiety disorders. Med J Aust 181(7 SUPPL.):S29-S46.
Mathie RT (2003) The research evidence base for homeopathy: a fresh assessment of the literature. Homeopathy 92:84-
91.
Seidl MM, Stewart DE (1998) Alternative treatments for menopausal symptoms. Systematic review of scientific and lay
literature. Can Fam Physician 44:1299-308.
a
Studies that were excluded as they received a ‘no’ rating for questions 3 or 7 of the AMSTAR measurement tool
A total of 68 specific clinical conditions were assessed in the systematic reviews included in this
overview and for the purposes of this report, were grouped into 15 broad therapeutic areas as
shown in Table 6.
Proctocolitis 1 1 20
Malaria 1 1 74
Postoperative pain-agitation 2 1 50
syndrome
Fibromyalgia 7 4 163
Osteoarthritis 3 5 998
Stroke 1 1 40
Personality disorder 1 0 0
Dementia 1 0 0
Depression 1 2 34
Heroin addiction 1 1 60
Asthma 6 8 675
Bronchitis 1 1 258
Cough 1 1 60
Sinusitis 2 3 420
Bruising 1 2 23
Eczema 2 1 277
Seborrhoeic dermatitis 1 1 41
Ulcers 2 2 123
Uraemic pruritis 1 1 28
Warts 4 3 277
Chemotherapy-associated 1 1 65
nausea/vomiting
Chemotherapy-induced stomatitis 3 2 59
Radiodermatitis in patients 3 1 66
undergoing radiotherapy
seborrhoeic dermatitis, ulcers, uraemic pruritis, and radiodermatitis in breast cancer patients
undergoing radiotherapy). Simonart et al (2011) provided a general descriptive assessment of the
body of evidence on homeopathy for dermatology. Overall, the authors concluded that “the
hypothesis that any dermatological condition responds convincingly better to homeopathic
treatment than to placebo or other control interventions is not supported by evidence. The evidence
in our overall analysis would be more compelling if there were independently replicated, large-scale
rigorous homeopathic trials. Until more compelling results are available, homeopathy cannot be
viewed as an evidence-based form of therapy in dermatology”.
concluded that “the hypothesis claiming that homeopathic Arnica is clinically effective beyond a
placebo effect is not based on methodologically sound placebo-controlled trials”.
Table 7 Matrix indicating the studies that were included in the systematic reviews of children with otitis media
Study ID
Jacobs et al Harrison (1999) Kruse (1998) Friese et al (1997)
(2001) [Level II] [Level III-2] [Level III-2]
[Level II]
NCC-WCH (2008)
Systematic review
[Level I]
Altunc e al (2007)
[Level I]
Bellavite et al (2011)
[Level I/III]
The National Collaborating Centre for Women’s and Children’s Health (2008) (hereafter referred to
as NCC-WCH, 2008) (AMSTAR score 6/10) performed a systematic review of the effectiveness of non-
surgical interventions in children with otitis media with effusion. The results of this review formed
the basis of a National Institute for Health and Care Excellence (NICE) clinical practice guideline. The
homeopathy search yielded one relevant Level II study that was given a rating of -1 (i.e. poor quality),
using the Scottish Intercollegiate Guidelines Network (SIGN) assessment tool. Harrison (1999) was a
pilot Level II study to determine if homeopathic treatment of children with otitis media with effusion
was more effective than standard care (i.e. “watchful waiting” with autoinflation and in some cases,
a course of low-dose antibiotics). After 12 months of follow up, there was no significant difference in
audiometric improvement between the two groups, but there was a significant difference in favour
of homeopathy for improvement in tympanograms. The systematic review noted, however, that this
Level II study was limited by the small sample size and no blinding of the participants. Importantly,
there was a significant difference in the level of initial hearing loss at baseline between children in
the treatment and placebo groups. NCC-WCH (2008) concluded that due to the lack of a published
evidence base, “homeopathy is not recommended for the management of otitis media with
effusion”.
The systematic review by Altunc et al (2007) (AMSTAR score 6/10) assessed the evidence for
homeopathy (and other therapeutic or preventive interventions) for childhood and adolescent
ailments. For the otitis media indication, one Level II study (with a Jadad score of 5) was included;
Jacobs et al (2001) investigated the effect of individualised homeopathic treatments in children with
acute otitis media compared with placebo. The study reported no significant difference in treatment
failures or the presence of middle ear effusion between the two groups. There was, however, a
significant decrease in symptom scores as recorded by parent diaries in the homeopathy group
compared with placebo. Altunc et al (2007) noted that these data require independent replication
and concluded that “the evidence from rigorous clinical trials of any type of therapeutic or
preventive intervention testing homeopathy for childhood and adolescence ailments is not
convincing enough for recommendations in any condition”.
Bellavite et al (2011) (AMSTAR score 5/10) aimed to evaluate the effectiveness of homeopathy for
the treatment of a range of diseases including infections of the upper airways and ear-nose-throat
ailments. One Level II study and two Level III-2 studies were included in the review for otitis media.
Bellavite et al (2011) reported that the Level II study by Jacobs et al (2001) found a non-significant
trend towards less treatment failure and a significant decrease in symptoms (p<0.05) in the
homeopathy group compared with placebo in children with acute otitis media. Both of the Level III-2
studies (Friese et al, 1997; Kruse, 1998) assessed the effect of individualised homeopathy in children
with otitis media. Kruse (1998) reported “equivalent efficacy” in homeopathy and conventional
therapies based on the duration of pain and therapy, and Friese et al (1997) found no significant
difference between individualised homeopathy and conventional therapy (antibiotics, mucolytics and
antipyretics) in mean duration of pain. Overall, Bellavite et al (2011) concluded there was “good
positive evidence” for individualised homeopathy in otitis media.
Reviewer comments
In addition to the trials described above, Bellavite et al (2011) took results from additional non-
controlled studies into account when they drew their conclusion of “good positive evidence” for
individualised homeopathy in otitis media. Those studies were not within the scope of this overview
and have therefore not been considered.
The quality of the studies included in the systematic review by Bellavite et al (2011) was also not
assessed by the authors. Based on the quality rating given by Altunc et al (2007), the evidence
reviewer assumes that Jacobs et al (2001) was a good-quality trial; however, the quality of the two
Level III-2 studies that were only reported by Bellavite et al (2011) is unknown.
Evidence statement
Two systematic reviews of poor and medium quality identified one small randomised controlled trial
(good quality; 75 participants) that compared homeopathy with placebo for the treatment of
children with acute otitis media. LOC: Low.
Based on only one small study there is no reliable evidence on which to draw a conclusion about the
effectiveness of homeopathy compared to placebo for the treatment of children with acute otitis
media.
Two systematic reviews of poor and medium quality identified one very small randomised controlled
trial (poor quality; 33 participants) and two prospectively designed, non-randomised controlled
studies (quality not reported; 126 and 131 participants) that compared homeopathy with other
therapies (antibiotics, mucolytics, secretolytics, antipyretics and nasal sprays) or watchful waiting for
the treatment of children with acute otitis media or otitis media with effusion.
These studies are of insufficient quality and/or size to warrant further consideration of their findings.
LOC: Very low - low.
Based on the body of evidence evaluated in this review there is no reliable evidence that
homeopathy is as effective as the other therapies for the treatment of children with acute otitis
media or otitis media with effusion.
Table 8 Evidence summary table: the effectiveness of homeopathy for the treatment of children with otitis media
Study ID Included study Patient population Intervention Comparator Outcome Results as Systematic review
Level of Level of reported in the interpretation
a a
evidence evidence systematic
b c review
Quality Quality
Sample size
NCC-WCH Harrison (1999) Children aged 18 Homeopathy Standard Audiometric No significant “Homeopathy is not
(2008) [Level II] months to 8 years with care improvement difference recommended for the
d a diagnosis of otitis (“watchful (hearing loss management of otitis media
[Level I] SIGN EL 1-
AMSTAR: 6/10 N=33 media with effusion by waiting” with <20 dB) with effusion.”
the patient’s general autoinflation
practitioner, hearing or a course Improvement Significant
SR of CAM for in difference in favour
acute otitis loss >20 dB and an of low-dose
abnormal antibiotics) tympanograms of homeopathy
media (p=0.01) (76.4%
tympanogram
versus 31.3%)
Altunc et al Jacobs et al (2001) Children with acute Individualised homeopathy, Placebo Symptom Significant “The evidence from rigorous
(2007) [Level II] otitis media non-material potencies, 5 scores (as difference in favour clinical trials of any type of
e
[Level I] Jadad score 5 Intervention group: mean days or until improvement recorded by of homeopathy therapeutic or preventive
AMSTAR: 6/10 N=75 age 3.5 years 8 different remedies in C30 parent diaries) (p<0.05) intervention testing
Control group: mean age potency; 4 most commonly homeopathy for childhood and
3.1 years used were Pulsatilla nigrans, Treatment No significant adolescence ailments is not
SR of 41% male Chamomilla, sulphur, Calcarea failures difference
homeopathy convincing enough for
Concomitant treatment: carbonica; 3-5 pellets 3 times
for multiple Presence of No significant recommendations in any
analgesics (10 in placebo daily
conditions group and 5 in middle ear difference condition.”
homeopathy group) effusion
(Note: this conclusion refers to
Adverse None all clinical conditions and is not
events specific to children with otitis
media)
Bellavite et al Jacobs et al (2001) Children with acute Individualised homeopathy Placebo Treatment Less failure in Good positive evidence for
(2011) [Level II] otitis media failure (5 days, homeopathy group, individualised homeopathy in
[Level I/III] Quality not 2 weeks, 6 non-significant otitis
AMSTAR: 5/10 specified weeks)
N=75
Symptom Significant
SR of scores (as decrease in
Study ID Included study Patient population Intervention Comparator Outcome Results as Systematic review
Level of Level of reported in the interpretation
a a
evidence evidence systematic
b c review
Quality Quality
Sample size
homeopathy recorded by symptoms in
for multiple parent diaries) homeopathy group
conditions compared to
placebo (p<0.05) at
24 and 64 hours
after treatment
Kruse (1998) Children with otitis Individualised homeopathy Conventional Duration of “Equivalent
[Level III-2] media therapies pain and efficacy” (3 days in
Quality not (antibiotics, therapy the homeopathy
specified secretolytics, group; 4 days in the
N=126 antipyretics conventional
and nasal therapy group)
sprays)
Recurrence No significant
difference (70.7% in
the homeopathy
group; 64% in the
conventional
therapy group)
Friese et al (1997) Children with otitis Individualised homeopathy Conventional Mean duration No significant
[Level III-2] media therapies of pain difference
Quality not (antibiotics,
specified mucolytics,
N=131 antipyretics)
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; CAM, complementary and alternative medicine; C, centesimal; dB, decibels; EL, evidence level; NCC-WCH, National
Collaborating Centre for Women’s and Children’s Health; SIGN, Scottish Intercollegiate Guidelines Network, SR, systematic review.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
d ++
SIGN evidence level assesses the quality of the evidence based on study design and risk of bias. The range of possible scores is 4 (low) to 1 (high). Studies with a level of evidence ‘–‘ should
not be used as a basis for making a recommendation due to high risk of bias.
e
The Jadad scale assesses the quality of published clinical trials based methods relevant to random assignment, double blinding and the flow of patients. The range of possible scores is zero
(bad quality) to 5 (good quality).
4.4.2 Glaucoma
The effectiveness of homeopathy for the treatment of patients with glaucoma was assessed in one
systematic review that formed the basis of a NICE clinical practice guideline on the diagnosis and
management of chronic open angle glaucoma and ocular hypertension (National Collaborating
Centre for Acute Care, 2009; AMSTAR score 3/5). The results of a literature search conducted in
August 2008 identified no studies that met the inclusion criteria.
Evidence statement
One systematic review (2008) did not identify any prospectively designed and controlled studies that
assessed the effectiveness of homeopathy in people with glaucoma.
Evidence statement
Two systematic reviews (2010, 2011) did not identify any prospectively designed and controlled
studies that assessed the effectiveness of homeopathy in children with constipation.
Table 9 Matrix indicating the studies that were included in the systematic reviews of diarrhoea
Study ID
Jacobs (2006) Jacobs Jacobs (1994) Jacobs (1993)
a
[Level II] (1997/2000) [Level II] [Level II]
[Level II]
NCC-WCH (2009)
[Level I]
Systematic review
Altunc et al (2007)
[Level I]
Cucherat et al (2000)
[Level I]
Linde and Melchart (1998)
[Level I]
a
Jacobs (1997) and Jacobs (2000) were the same study. The study was referred to as Jacobs (1997) in Linde and Melchart
(1998) and Jacobs (2000) in NCC-WCH (2009) and Altunc et al (2007).
The National Collaborating Centre for Women’s and Children’s Health (2009) (hereafter referred to
as NCC-WCH, 2009; AMSTAR score of 5/10) performed a systematic review of alternative or
complementary therapies in the treatment of gastroenteritis. The results of this review formed the
basis of a NICE clinical practice guideline on diarrhoea and vomiting caused by gastroenteritis. One
review and one good-quality Level II study were included. Jacobs (2006) was a Level II study that
investigated the effect of homeopathic combination therapy tablets in children aged between 5
months and 6 years who had acute diarrhoea. The study found no significant difference between
homeopathy and placebo for the duration of diarrhoea, mean rate of unformed stool passage per
day, or total number of unformed stools during follow-up. NCC-WCH (2009) also considered the
results of a review1 and meta-analysis (Jacobs et al, 2003) that included the Level II studies by Jacobs
(1993), Jacobs (1994) and Jacobs (2000). Overall, NCC-WCH (2009) concluded “the clinical trials
assessing homeopathy had significant methodological limitations. Moreover, there was a lack of
consistency in the evidence. Therefore, no recommendation was made for the use of homeopathy”.
The systematic review by Altunc et al (2007) (AMSTAR score of 6/10) assessed the evidence of any
type of therapeutic or preventive intervention testing homeopathy for childhood and adolescent
ailments. Three Level II studies (each assigned a Jadad score of 5 by Altunc et al) were identified for
the treatment of children with diarrhoea (Jacobs, 2000; Jacobs, 1994; Jacobs, 1993). All three Level II
studies were similar in design and tested individualised homeopathy in acute childhood diarrhoea.
Two Level II studies (Jacobs, 2000; Jacobs, 1994) reported significant effects in favour of homeopathy
1
This review was excluded for the purposes of the current overview as the included studies were not identified by
systematic means.
for the duration of diarrhoea and the number of unformed stools. The third Level II study (Jacobs,
1993) found no significant differences between homeopathy and placebo for either of these
outcomes. Altunc et al (2007) concluded that “the evidence from rigorous clinical trials of any type of
therapeutic or preventive intervention testing homeopathy for childhood and adolescence ailments
is not convincing enough for recommendations in any condition”.
Cucherat et al (2000) (AMSTAR score 10/11) aimed to answer the question of “whether there is any
evidence from randomised controlled trials that homeopathy is efficacious for the treatment of
disease in humans”. One Level II study (Jacobs, 1994) was identified for the childhood diarrhoea
indication. Similar to the other systematic reviews, Cucherat et al (2000) also reported that there was
a significant effect of homeopathy (p=0.048) in the duration of diarrhoea. The quality of Jacobs
(1994) was not formally assessed by Cucherat et al (2000); however, a general comment was made
about all of the included studies that “the strength of this evidence is low because of the low
methodological quality of the trials”. Cucherat et al (2000) also noted that the studies of high
methodological quality were more likely to provide negative results for homeopathy compared to
the lower quality studies. Overall, the authors concluded that “it is clear that the strength of available
evidence is insufficient to conclude that homeopathy is clinically effective”.
In addition, Cucherat et al (2000) conducted several meta-analyses with different combinations of
studies (based on attributes such as blinding, attrition and type of homeopathic preparation).
However, the authors acknowledge that “the meta-analysis method used does not allow any
conclusion on what homeopathic treatment is effective in which diagnosis or against which
symptoms”. For that reason, the results of the meta-analyses will not be discussed in detail in the
remainder of this report.
Linde and Melchart (1998) (AMSTAR score of 8/11) examined the state of clinical efficacy research on
individualised homeopathy and identified three Level II studies (Jacobs, 1993; Jacobs, 1994; Jacobs,
1997) for the childhood diarrhoea indication. Consistent with all of the above systematic reviews,
Linde and Melchart (1998) reported a significant effect of homeopathy in all of the primary outcomes
measured in Jacobs (1994). The authors of the systematic review also noted that there were
“positive trends, but no significant inter-group differences” between homeopathy and placebo in
Jacobs (1993). Jacobs (1997), reported elsewhere as Jacobs (2000), was a Level II study that tested
the effect of individualised homeopathy in children with diarrhoea. The study found no significant
difference between the homeopathy and placebo groups.
A meta-analysis of all included studies for all clinical conditions (not specific to children with
diarrhoea) conducted by Linde and Melchart (1998) found an overall trend in favour of homeopathy
(RR 1.62; 95% CI 1.17, 2.23). However, the pooled rate ratio of the “methodologically best” studies
(which included Jacobs, 1994) was clearly smaller and no longer statistically significant (RR 1.12; 95%
CI 0.87, 1.44). The pooled findings are unlikely to be of value due to the highly heterogeneous group
of studies and conditions that were included in the meta-analyses. As such, the results of the meta-
analyses conducted by Linde and Melchart (1998) will not be discussed in detail in the remainder of
this report. Overall, Linde and Melchart (1998) concluded that any evidence suggesting that
homeopathy has an effect over placebo is “not convincing because of methodological shortcomings
and inconsistencies”.
Reviewer comments
The current evidence base for homeopathy for the treatment of children with diarrhoea is limited by
the fact that all of the identified studies were carried out by the same research group.
Evidence statement
Four systematic reviews of poor to good quality identified four randomised controlled trials (medium
to good quality; total of 544 participants, range: 34-292), all conducted by the same research group,
that compared homeopathy with placebo for the treatment of children with diarrhoea.
The one medium-sized, good-quality trial (292 participants) did not detect a difference between
combined homeopathy and placebo in the treatment of children with diarrhoea.
The studies of individualised homeopathy are of insufficient quality and/or size to warrant further
consideration of their findings. LOC: Low - moderate.
Based on the body of evidence evaluated in this review combined homeopathy is not more effective
than placebo for the treatment of children with diarrhoea and there is no reliable evidence that
individualised homeopathy is more effective than placebo for the treatment of children with
diarrhoea.
Table 10 Evidence summary table: the effectiveness of homeopathy for the treatment of children with diarrhoea
Study ID Included Patient population Intervention Comparator Outcome Results as Systematic review
Level of study reported in the interpretation
a
evidence Level of systematic
b a
Quality evidence review
c
Quality
Sample size
NCC-WCH Jacobs (2006) Children aged between Homeopathic combination Placebo Duration of No significant "The Guidelines Development
(2009) [Level II] 5 months and 6 years therapy tablets (Arsenicum diarrhoea difference Group considered that the
d
[Level I] SIGN EL 1+ who had acute album, Calcarea carbonica, clinical trials assessing
diarrhoea (defined as chamomilla, podophyllum Mean rate of No significant homeopathy had significant
AMSTAR: 5/10 N=292
the passage of three or and sulphur – in a liquid unformed stool difference methodological limitations.
more unformed stools homeopathic dilution in the passage per Moreover, there was a lack of
SR of CAM for day during
childhood in the previous 24 30C potency) consistency in the evidence.
hours) that was follow up Therefore, no
diarrhoea
confirmed visually by Total number No significant recommendation was made
study staff of unformed difference for the use of homeopathy.”
stools during
follow up
e
Altunc et al Jacobs (2000) Children with 19 different remedies in 30C Placebo Number of days Significant effect in "The evidence from rigorous
(2007) [Level II] diarrhoea potency, one dose after every with diarrhoea favour of clinical trials of any type of
[Level I] Jadad score 5
f Intervention: mean age unformed stool for 5 days; 5 homeopathy therapeutic or preventive
AMSTAR: 6/10 N=126 1.7 years most common: Podophyllum, (p=0.04) intervention testing
Control: mean age 1.4 sulphur, Arsenicum album, homeopathy for childhood
years Calcarea carbonica, Number of Significant effect in and adolescence ailments is
SR of 67.5% male daily stools favour of
homeopathy for Chamomilla not convincing enough for
Concomitant treatment: homeopathy
multiple recommendations in any
oral rehydration therapy, (p=0.02)
conditions normal feeding;
condition.”
standard antiparasitic
medication at end of (Note: this conclusion refers
intervention if needed to all clinical conditions and is
Study ID Included Patient population Intervention Comparator Outcome Results as Systematic review
Level of study reported in the interpretation
a
evidence Level of systematic
b a
Quality evidence review
c
Quality
Sample size
Jacobs (1994) Children with 18 different remedies in 30C Placebo Number of days Significant effect in not specific to childhood
[Level II] diarrhoea potency, one dose after every with diarrhoea favour of diarrhoea)
Jadad score 5
f Intervention: mean age unformed stool for 5 days: homeopathy
N=92 1.6 yr Podophyllum, Chamomilla, (p=0.048)
Control: mean age 1.5 yr Arsenicum album, Calcarea
Concomitant treatment: carbonica, sulphur, Mercurius Number of Significant effect in
oral rehydration therapy, vivus, Pulsatilla, phosphorus, daily stools favour of
normal feeding;
China, Gambogia, Aethusia, homeopathy
standard antiparasitic
medication at the end of aloe, belladonna, Bryonia, difference (p<0.05)
intervention if needed; Colchicum, Croton tiglium,
Dulcamara, Nux vomica Adverse events No adverse events
11 children were given
antidiarrheal medication
by their parents (6 in
placebo group; 5 in
homeopathy group)
Jacobs (1993) Children aged between Various remedies in 30C Placebo Number of days No significant
[Level II] 6 months to 5 years potency (no details reported), with diarrhoea difference
f with diarrhoea 2 pills daily for 3 days or until
Jadad score 5
Concomitant treatment: improvement Number of No significant
N=34 daily stools difference
oral rehydration therapy,
normal feeding;
standard antiparasitic
medication at the end of
intervention if needed
Cucherat et al Jacobs (1994) Children with acute Individualised homeopathy Placebo Number of days Significant "It is clear that the strength of
(2000) [Level II] childhood diarrhoea with diarrhoea difference in available evidence is
[Level I] Quality not favour of insufficient to conclude that
AMSTAR: 10/11 specified homeopathy homeopathy is clinically
N=92 (81 (p=0.048) effective.”
SR of evaluated)
homeopathy for (Note: this conclusion refers
multiple to all clinical conditions and is
Study ID Included Patient population Intervention Comparator Outcome Results as Systematic review
Level of study reported in the interpretation
a
evidence Level of systematic
b a
Quality evidence review
c
Quality
Sample size
conditions not specific to childhood
diarrhoea)
e
Linde and Jacobs (1997) Children with Fully individualised, computer- Placebo Number of days No significant Conclusion of the systematic
Melchart (1998) [Level II] diarrhoea assisted (RADAR) choice of with diarrhoea difference review:
[Level I] Quality not remedy, taken as C30 after A meta-analysis found an
AMSTAR: 8/11 specified each unformed stool overall trend in favour of
N=126 homeopathy.
SR of 1. The rate ratio was 1.62 (95% CI
Jacobs (1994) Children with Fully individualised, computer- Placebo Number of days Significant 1.17 to 2.23) and the odds ratio
homeopathy for
[Level II] diarrhoea assisted (RADAR) choice of with diarrhoea difference was 2.62
multiple g 2. The pooled rate ratio of the
Quality: 5,5 remedy, taken as C30 after between groups
conditions methodologically best studies
N=92 each unformed stool (p<0.05)
was clearly smaller and not
Intervention: 3.0
statistically significant (1.12,
days
95% CI 0.87, 1.44). This meta-
Control: 3.8 days
analysis included Jacobs (1994).
Days to first “Homeopathy 3. The rate ratio of the six studies
formed stool significantly published in MEDLINE-listed
journals was not significantly
better” (p-value
different from placebo (1.22,
not reported) 95% CI 0.94, 1.56). This meta-
analysis included Jacobs (1994)
Diarrhoea score “Homeopathy
significantly
better” (p-value (Note: results of meta-analysis
not reported) refer to all clinical conditions
and are not specific to
Jacobs (1993) Children with Fully individualised computer- Placebo Number of days Positive trends, diarrhoea)
[Level II] diarrhoea assisted (RADAR) choice of with diarrhoea but no significant
g remedy, taken as C30 twice inter-group
Quality: 3,3
N=34 daily for 3 days differences
(p=0.28)
Intervention: 2.4
days
Study ID Included Patient population Intervention Comparator Outcome Results as Systematic review
Level of study reported in the interpretation
a
evidence Level of systematic
b a
Quality evidence review
c
Quality
Sample size
Control: 3.0 days
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; C, centesimal; CAM, complementary and alternative medicines; EL, Evidence level; SIGN, Scottish Intercollegiate
Guidelines Network; SR, systematic review.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
d ++
SIGN evidence level assesses the quality of the evidence based on study design and risk of bias. The range of possible scores is 4 (low) to 1 (high). Studies with a level of evidence ‘–‘
should not be used as a basis for making a recommendation due to high risk of bias.
e
Jacobs (1997) and Jacobs (2000) were the same study. The study was referred to as Jacobs (1997) in Linde and Melchart (1998) and Jacobs (2000) in NCC-WCH (2009) and Altunc et al
(2007).
f
The Jadad scale assesses the quality of published clinical trials based methods relevant to random assignment, double blinding and the flow of patients. The range of possible scores is zero
(bad quality) to 5 (good quality).
g
Quality was assessed using (i) Jadad score, out of five; (ii) internal validity score, out of six.
Evidence statement
Two systematic reviews (1998, 2008) did not identify any prospectively designed and controlled
studies that assessed the effectiveness of homeopathy compared with placebo for the treatment of
people with irritable bowel syndrome.
One systematic review of medium quality identified one very small randomised controlled trial (poor
quality; 23 participants) that compared homeopathy (Simillimum) with other therapies (dicyclomine
hydrochloride, faecal bulking agents and diet advice) for the treatment of people with irritable bowel
syndrome. LOC: Very low.
Based on only one very small poor quality study there is no reliable evidence on which to draw a
conclusion about the effectiveness of homeopathy compared to the other therapies for the
treatment of people with irritable bowel syndrome.
Table 11 Evidence summary table: the effectiveness of homeopathy for the treatment of irritable bowel syndrome
Study ID Included study Patient Intervention Comparator Outcome Results as reported in Systematic review interpretation
Level of Level of population the systematic review
a a
evidence evidence
b c
Quality Quality
Sample size
Linde and Lecoyte et al Patients with Individualised Dicyclomine Unclear “Similar improvements in No specific conclusions were provided
Melchart (1993) irritable bowel simillimum hydrochloride, both groups” regarding the efficacy of homeopathy for
(1998) [Level II] syndrome (all faecal bulking irritable bowel syndrome.
d
[Level I] Quality: 1, 1.5 female; 20-69 agents, diet
AMSTAR: 8/11 N=23 years of age) advice The trial was of poor quality due to an
insufficient sample size and no blinding.
SR of
homeopathy
for multiple
conditions
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; SR, systematic review.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
d
Quality was assessed using (i) Jadad score, out of five; (ii) internal validity score, out of six.
Table 12 Matrix indicating the studies that were included in the systematic reviews of postoperative ileus
Systematic review
Cucherat et al (2000) Barnes et al (1997) Linde et al (1997)
[Level I] [Level I] [Level I]
GRECHO
(1987/1989)
[Level II]
Aulagnier (1985)
[Level II]
Chevrel (1984)
[Level II]
Study ID
Estrangin (1983)
[Level II]
Valero (1981)
[Level II]
Dorfman (1992)
[Level III-2]
Castelin (1979)
[Level III-2]
Cucherat et al (2000) (AMSTAR score 10/11) aimed to answer the question of “whether there is any
evidence from randomised controlled trials that homeopathy is efficacious for the treatment of
disease in humans”. The review included the results of GRECHO (Groupe de Rechereche et d’Essais
Cliniques en Homeopathie) (1989), which was a three-armed Level II study that examined the effect
of homeopathic Opium or homeopathic Raphanus and Opium compared with placebo in patients
with postoperative ileus. The study found no significant difference in the delay to first stool between
homeopathy and placebo groups, in either intervention arm. Cucherat et al (2000) concluded that "it
is clear that the strength of available evidence is insufficient to conclude that homeopathy is clinically
effective".
Barnes et al (1997) (AMSTAR score of 6/11) performed a systematic review and meta-analysis of
controlled trials "to determine if homeopathic treatment has any greater effect than placebo
treatment in the restoration of intestinal peristalsis in patients after abdominal or gynaecologic
surgery". Six prospectively designed and controlled studies were included in the analysis (Aulagnier,
1985; Castelin, 1979; Chevrel, 1984; Dorfman 1992; GRECHO, 1989; Valero, 1981), however the
evidence reviewer notes that this includes a mix of Level II and Level III-2 studies. A seventh study
(Estrangin, 1983) was excluded as the data were expressed in an inappropriate form for meta-
analysis. Quantitative results of the time to first flatus and time to first faeces were presented for all
of the included studies where applicable; however, any statistical significance of the data was not
Prepared for the NHMRC Homeopathy Working Committee by Optum 45
EFFECTIVENESS OF HOMEOPATHY FOR CLINICAL CONDITIONS: OVERVIEW REPORT October 2013
specified. Rather, Barnes et al (1997) descriptively noted that all of the studies (with the exclusion of
GRECHO, 1989) reported a "positive" effect for homeopathy, compared with placebo, on the time to
first flatus. The Level II study by GRECHO (1989) found "no effect" for homeopathy in this respect.
Two of the four studies that also measured time to first faeces reported a positive effect for
homeopathy (Castelin, 1979; Aulagnier, 1985), one reported a "statistically non-significant" mean
reduction in time to first faeces in patients who received homeopathy (Chevrel, 1984) and one Level
II study reported no difference between homeopathy and placebo (GRECHO, 1989).
A meta-analysis of all six included studies revealed a statistically significant effect in favour of
homeopathy for time to first flatus (weighted mean difference (WMD) -7.4; 95% CI -4.0 to -10.8;
p<0.05). This effect remained even with the exclusion of the two low quality studies (Castelin, 1979;
Dorfman, 1992) (WMD -6.11; 95% CI -2.31 to -9.91; p<0.005). A significant effect in favour of
homeopathy was also found for time to first flatus when a homeopathic remedy of less than 12C
potency was used (4 studies; WMD -6.6; 95% CI -2.6 to -10.5; p<0.05). However, there was no
significant difference in time to first flatus with homeopathic remedies greater than 12C potency (3
studies; WMD -3.1; 95% CI -7.5 to 1.3). Barnes et al (1997) warned that the results of the meta-
analysis "must be interpreted with caution" as the included studies had a number of limitations.
Notably, two of the studies were non peer-reviewed theses (Castelin, 1979; Valero, 1981) and
heterogeneity was evident in the included studies. Overall, Barnes et al (1997) concluded that "there
is some evidence to support the administration of a homeopathic remedy immediately after surgery
to reduce the duration of ileus. However, there is no evidence to support the use of a particular
homeopathic remedy or for a combination of remedies".
Linde et al (1997) (AMSTAR score 9/11) conducted a systematic review and meta-analysis that aimed
to “assess whether the effect seen with homeopathic remedies is equivalent to that seen with
placebo”. Six prospectively designed and controlled studies were included in the analysis for
postoperative ileus (Aulagnier, 1985; Chevrel, 1984; Dorfman 1992; Estrangin, 1983; GRECHO, 1987;
Valero, 1981). The result of a single outcome for each study was presented as a forest plot of odds
ratios. The numerical odds ratio was not presented and the input data to calculate the odds ratios
were not provided. A graphical interpretation of the forest plot suggested a positive effect of
homeopathy for the primary outcome of three included studies (Aulagnier, 1985; Chevrel, 1984;
Dorfman, 1992). There appeared to be no difference between homeopathy and placebo in the
remaining three studies (Estrangin, 1983; GRECHO, 1987; Valero, 1981).
A meta-analysis of all included studies (excluding Estrangin, 1983) also found a statistically significant
difference in time to first flatulence (Cohen's d -0.22; 95% CI -0.36 to -0.09). Similarly, there was a
significant difference in time to first stool (Cohen's d -0.18; 95% CI -0.33 to -0.03).The overall
conclusion by Linde et al (1997) was that there was “insufficient evidence” that homeopathy is
“clearly efficacious for any single clinical condition”.
Evidence statement
Three systematic reviews of medium to good quality identified five randomised controlled trials
(poor to good quality; total of 1095 participants, range: 96-600) and two prospectively designed,
non-randomised controlled studies (poor to medium quality; 20 and 80 participants) that compared
homeopathy with placebo for the treatment of people with postoperative ileus.
Two of the systematic reviews conducted meta-analyses that found a significant difference in favour
of homeopathy, but both meta-analyses included a number of poor quality studies with a high risk of
bias. The one large, good-quality trial (600 participants) did not detect a difference between
homeopathy and placebo in the treatment of postoperative ileus. LOC: Moderate.
Based on the body of evidence evaluated in this review homeopathy is not more effective than
placebo for the treatment of people with postoperative ileus.
Table 13 Evidence summary table: the effectiveness of homeopathy for the treatment of postoperative ileus
Study ID Included study Patient population Intervention Comparator Outcome Results as reported in Systematic review
Level of Level of the systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
e
Cucherat et al GRECHO (1989) Patients with post- Opium 15 °C Placebo Time to first No significant difference “It is clear that the strength of
(2000) [Level II] surgery ileus faeces (hr) (p=0.699) available evidence is insufficient to
[Level I] Quality not e conclude that homeopathy is
Patients with post- Raphanus 15 °C Placebo Time to first No significant difference clinically effective”
AMSTAR: specified
d surgery ileus and Opium 15 faeces (hr) (p=0.358)
10/11 N=450 °C
(Note: this conclusion refers to all
SR of clinical conditions and is not
homeopathy specific to postoperative ileus)
for multiple
conditions
Barnes et al GRECHO (1989) Patients with Opium 15C Placebo Time to first Mean (SD) Interpretation of the included Level
(1997) [Level II] postoperative ileus flatus (hr) Intervention group: 54.2 (24.7) II studies:
[Level I] Quality: 90/100
g after abdominal or Control group: 52.3 (26.8) “Our analyses suggest that
AMSTAR: 6/11 N=600
f gynaecologic surgery Significance NR homeopathic treatment
administered immediately after
Time to first Mean (SD)
SR of abdominal surgery may reduce the
faeces (hr) Intervention group: 96.2 (39.8)
homeopathy time to first flatus when compared
Control group: 94.4 (40.7)
for with placebo administration. They
Significance NR
postoperative do not provide evidence for the use
ileus Opium 15C + No treatment Time to first Mean (SD) of a particular homeopathic
Raphanus flatus (hr) Intervention group: 54.8 (26.1) remedy or for a combination of
sativus 5C Control group: 56.6 (26.3) remedies for postoperative ileus.”
Significance NR
Conclusion of the systematic
Time to first Mean (SD)
review:
faeces (hr) Intervention group: 98.8 (42)
Control group: 95.4 (23.7)
A meta-analysis of the results
Significance NR found:
A significant effect in favour of
Aulagnier (1985) Patients with Opium 9C + Placebo Time to first Mean (SD) homeopathy for time to first flatus
[Level II] postoperative ileus Arnica Montana (unmedicated flatus (hr) Intervention group: 59.28 (21.36) when all studies were included
after abdominal or 9C + Raphanus granules) Control group: 76.08 (30) (WMD -7.4; 95% CI -4.0, -10.8; p<0.05).
Study ID Included study Patient population Intervention Comparator Outcome Results as reported in Systematic review
Level of Level of the systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
g
Quality: 75/100 gynaecologic surgery sativus 9C Significance NR A significant effect in favour of
N=200 homeopathy for time to first flatus
when 2 low quality studies were
excluded
Time to first Mean (SD) (WMD -6.11; 95% CI -2.31, -9.91;
faeces (hr) Intervention group: 96.96 (34.08) p<0.05)
Control group: 117.12 (38.4) A significant effect in favour of
homeopathy for time to first flatus
Significance NR
with homeopathic remedy of <12C
Chevrel (1984) Patients with Opium 15C Placebo Time to first Mean (SD) potency
(WMD -6.6; 95% CI -2.6, -10.5;
[Level II] postoperative ileus (unmedicated flatus (hr) Intervention group: 42.7 (21.9)
p<0.05)
Quality: 58/100
g after abdominal or granules) Control group: 52.0 (22.0)
No significant difference in time to first
N=96 gynaecologic surgery Significance NR flatus with homeopathic remedy of
≥12C potency
Time to first No significant difference.
(WMD -3.1; 95% CI -7.5, 1.3)
faeces (hr) Mean (SD)
Intervention group: 78.2 (30.5)
Control group: 99.9 (37.9)
Valero (1981) Patients with Raphanus Placebo Time to first Mean (SD)
[Level II] postoperative ileus sativus 7C (unmedicated flatus (hr) Intervention group: 53.3 (25.02)
Quality: 80/100
g after abdominal or granules) Control group: 58.6 (22.27)
N=80 gynaecologic surgery Significance not reported
Dorfman (1992) Patients with China regia 5C + Placebo (drops – Time to first Mean (SD)
[Level III-2] postoperative ileus Arnica montana alcohol diluted in flatus (hr) Intervention group: 46.5 (23.5)
Quality: 50/100
g after abdominal or 9C + Raphanus water) Control group: 62 (28)
N=80 gynaecologic surgery sativus 5C Significance NR
Castelin (1979) Patients with Opium 15C Placebo Time to first Mean (SD)
[Level III-2] postoperative ileus (unmedicated flatus (hr) Intervention group: 24.9 (8.6)
Quality: 20/100
g after abdominal or granules) Control group: 34.8 (14.2)
Significance NR
Study ID Included study Patient population Intervention Comparator Outcome Results as reported in Systematic review
Level of Level of the systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
N=20 gynaecologic surgery Time to first Mean (SD)
faeces (hr) Intervention group: 83.7 (21.6)
Control group: 110.8 (37.1)
Significance NR
Linde et al GRECHO (1987) Patients with Opium C15 Placebo Time to first Odds ratio showed no Conclusion of the systematic
(1997) [Level II] postoperative ileus (+C15, Raph C5 flatus <2 days difference between review:
h homeopathy and placebo
[Level I] Quality: 80/86 A meta-analysis of all included
AMSTAR: 9/11 N=450 studies (excluding Estrangin, 1983)
found:
Aulagnier (1985) Patients with Opium C9, Placebo Global Odds ratio favoured A significant difference between
SR of
[Level II] postoperative ileus Raph. C9, Arnica assessment, homeopathy homeopathy and placebo in time to
homeopathy h
Quality: 40/64 C9 patient first flatulence
for multiple
(Cohen’s d -0.22; 95% CI -0.36, -0.09)k
conditions N=200
A significant difference between
Chevrel (1984) Patients with Opium C15 Placebo Time to first Odds ratio favoured homeopathy and placebo in time to
postoperative ileus faeces homeopathy first stool
[Level II]
h (Cohen’s d -0.18; 95% CI -0.33, -0.03)k
Quality: 40/71
N=96
Estrangin (1983) Patients with Arnica C7, China Placebo Time to flatus Odds ratio showed no
[Level II] postoperative ileus C7, Pyrog C5 <2 days difference between
h homeopathy and placebo
Quality: 40/43
N=97
Valero (1981) Patients with Raphanus C7 Placebo Time to first Odds ratio showed no
i
[Level II] postoperative ileus faeces difference between
h homeopathy and placebo
Quality: 80/64
N=102
j
Dorfman (1992) Patients with Complex Placebo Patients Odds ratio favoured
[Level III-2] postoperative ileus without pain homeopathy
Study ID Included study Patient population Intervention Comparator Outcome Results as reported in Systematic review
Level of Level of the systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
h
Quality: 40/36
N=80
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; C, centesimal; CI, confidence interval; NR, not reported; SD, standard deviation; SR, systematic review; WMD, weighted
mean difference.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
d
According to Cucherat et al (2000) the same control group was used for comparisons with both active arms.
e
Identically prepared globules (without active constituent)
f
According to Barnes et al (1997) the trial included four arms with 150 patients in each arm.
g
Quality scoring system described by Kleijnen et al (1991). A score of ≥55 indicates a study of higher quality.
h
Jadad score / IV score, where the scores are expressed as a percentage of the maxium possible score. Note: the maximum possible Jadad score is 5; the maximum possible internal validity
score is 7.
i
Trials with continuous outcomes (converted to odds ratios).
j
No further information about this homeopathic remedy was provided.
k
The publication by Linde et al (1997) contained a discrepancy in the reporting of this result. The confidence interval reported in Table 5 of the publication suggested a non-significant
difference (e.g. 95% confidence interval: -0.36, 0.09), whereas the confidence interval reported in the text suggested a significant difference (e.g. 95% confidence interval: -0.36, -0.09) between
the treatment groups. An effort was made to contact the authors to clarify the discrepancy; however, no response was received. In the absence of a response from the authors it was assumed
that the results in the text of the systematic review were correct.
4.5.5 Proctocolitis
The effectiveness of homeopathy for the treatment of patients with procotocolitis was assessed in
one systematic review (Linde and Melchart, 1998; AMSTAR score 8/11) as summarised in Table 14.
The authors conducted a broad review of the efficacy of individualised homeopathy across a range of
clinical areas. One Level II study was identified that assessed the efficacy of individualised
homeopathic simillimum (C30, C100 or C200) compared with placebo or salazopyrine and
aminosalicylic acid (ASA) for the treatment of proctocolitis (Janssen et al, 1992). The outcome
measure used to assess efficacy was not clear to the authors of the systematic review; however, they
suggested that “conventional therapy seemed most effective”. Linde and Melchart (1998) stated that
the study was “totally uninterpretable” and also flawed due to very poor recruitment. Overall, the
authors of the systematic review concluded that, across all clinical conditions, any evidence
suggesting that homeopathy has an effect is “not convincing because of methodological
shortcomings and inconsistencies”.
Evidence statement
One systematic review of medium quality identified one very small randomised controlled trial
(medium quality; 20 participants) that compared homeopathy (Simillimum) with placebo and other
therapies (salazopyrine and aminosalicylic acid) for the treatment of people with proctocolitis. LOC:
Very low.
Based on only one very small study there is no reliable evidence on which to draw a conclusion about
the effectiveness of homeopathy compared to placebo or the other therapies for the treatment of
people with proctocolitis.
Table 14 Evidence summary table: the effectiveness of homeopathy for the treatment of proctocolitis
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Linde and Janssen et al Patients with Individual Salazopyrine + Unclear “Hard to interpret – but “Well-planned trial; recruitment
Melchart (1998) (1992) proctocolitis (55% simillimum once ASA, or placebo conventional therapy seemed failed completely – totally
[Level I] [Level II] female; age 19 to in C30, C200 or most effective.” uninterpretable.”
d 69 years) C100
AMSTAR: 8/11 Quality: 4,3.5
N=20
SR of
homeopathy for
multiple
conditions
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; ASA, aminosalicylic acid; C, centesimal; SR, systematic review.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
d
Quality assessed using (i) Jadad score (out of 5); (ii) internal validity score (out of 6).
Evidence statement
One systematic review (2010) did not identify any prospectively designed and controlled studies that
assessed the effectiveness of homeopathy in children with nocturnal enuresis.
Evidence statement
One systematic review (2009) did not identify any prospectively designed and controlled studies that
assessed the effectiveness of homeopathy in men with lower urinary tract symptoms.
Reviewer comments
The evidence reviewer notes that the trial by Solanki and Gandhi (1995) was included in the meta-
analysis by Linde and Melchart (1998); however, the meta-analysis has not been discussed in detail in
this summary. The relevance of the pooled results to the treatment of amebiasis and giardiasis is
limited due to the fact that the trial was only one of 19 studies included in the meta-analysis, all of
which examined different clinical conditions and a variety of homeopathic remedies.
Evidence statement
One systematic review of medium quality identified one very small randomised controlled trial
(medium quality; 34 participants) that compared homeopathy (Simillimum) with placebo for the
treatment of people with amebiasis and giardiasis. LOC: Very low.
Based on only one very small study there is no reliable evidence on which to draw a conclusion about
the effectiveness of homeopathy compared to placebo for the treatment of people with amebiasis
and giardiasis.
Table 15 Evidence summary table: the effectiveness of homeopathy for the treatment of amebiasis and giardiasis
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review interpretation
Level of Level of population systematic review
a a
evidence evidence
b c
Quality Quality
Sample size
Linde and Solanki and Patients with Individual Placebo Number cured Better response in homeopathy Comments regarding the included Level II
Melchart (1998) Gandhi (1995) amebiasis and simillimum (physician group: study:
[Level I] [Level II] giardiasis (all assessed) Intervention group: 11/19 (58%) “Insufficient report; completely unclear
AMSTAR: 8/11 Jadad score 3
d
female; age Control group: 2/15 (13%) how response/cure was
N=34 range 4 to 35 Rate ratio (95% CI): 4.34 (1.13, 16.7) established/defined; extremely positive
SR of years) results.”
homeopathy
for multiple Conclusion of the systematic review:
conditions A meta-analysis found an overall trend in
favour of homeopathy.
The rate ratio was 1.62 (95% CI 1.17 to 2.23)
and the odds ratio was 2.62
The pooled rate ratio of the methodologically
best studies was clearly smaller and not
statistically significant (1.12, 95% CI 0.87, 1.44)
The rate ratio of the six studies published in
MEDLINE-listed journals was not significantly
different from placebo (1.22, 95% CI 0.94,
1.56)
4.7.2 Cholera
The effectiveness of homeopathy for the treatment of cholera was assessed in one systematic review
(Linde and Melchart, 1998; AMSTAR score 8/11) as summarised in Table 16. Linde and Melchart
(1998) examined the efficacy of homeopathy in a number of chronic conditions and infectious
diseases. The systematic review identified one Level II study (with a Jadad score of 2) that specifically
examined homeopathic remedies (one of eight pre-selected options) as a treatment for cholera,
compared with placebo (Gaucher et al, 1994). Linde and Melchart (1998) reported that “no
significant differences” were observed; however the primary outcome examined in the study was not
reported in the systematic review, so the result provides no meaningful evidence for the treatment
of cholera with homeopathy.
Linde and Melchart (1998) indicated that the Level II study by Gaucher et al (1994) was a poor-quality
trial, was poorly-reported, and contained a very limited amount of useful data. As such, they
excluded the trial from their meta-analysis. Overall, Linde and Melchart (1998) concluded that, across
all clinical conditions, any evidence suggesting that homeopathy has an effect over placebo is “not
convincing because of methodological shortcomings and inconsistencies”.
Reviewer comments
The most informative finding presented by Linde and Melchart (1998) was that there were “no
significant differences”; however, it was unclear to the evidence reviewer whether the null result
alluded to differences within the homeopathy arm (from baseline to follow-up) or differences
between treatment arms (homeopathy versus placebo). The evidence reviewer made the assumption
that the results referred to an absence of significant differences between the homeopathy and
placebo treatment arms.
Evidence statement
One systematic review of medium quality identified one very small randomised controlled trial (poor
quality; 44 participants) that compared homeopathy with placebo for the treatment of people with
cholera. LOC: Very low.
Based on only one very small poor quality study there is no reliable evidence on which to draw a
conclusion about the effectiveness of homeopathy compared to placebo for the treatment of people
with cholera.
Table 16 Evidence summary table: the effectiveness of homeopathy for the treatment of cholera
Study ID Included study Patient Intervention Comparator Outcome Results as reported Systematic review interpretation
a
Level of Level of evidence population in the systematic
a c
evidence Quality review
b
Quality Sample size
Linde and Gaucher et al (1994) Patients Most indicated Placebo Not reported No significant Interpretation of the included Level II study:
Melchart (1998) [Level II] with cholera homeopathic differences Due to insufficient reporting, a reliable and valid
d
[Level I] Jadad score 2 remedy chosen assessment of this trial was not possible
e from 8
AMSTAR: 8/11 N=44
preselected Conclusion of the systematic review:
SR of options A meta-analysis found an overall trend in favour
homeopathy for of homeopathy.
multiple The rate ratio was 1.62 (95% CI 1.17 to 2.23)
conditions and the odds ratio was 2.62
The pooled rate ratio of the methodologically
best studies was clearly smaller and not
statistically significant (1.12, 95% CI 0.87, 1.44)
The rate ratio of the six studies published in
MEDLINE-listed journals was not significantly
different from placebo (1.22, 95% CI 0.94, 1.56)
Evidence statement
One systematic review of medium quality identified two randomised controlled trials (poor quality;
12 and 100 participants) that compared homeopathy with placebo for the treatment of people with
human immunodeficiency virus.
These studies are of insufficient quality and size to warrant further consideration of their findings.
LOC: Very low - low.
Based on the body of evidence evaluated in this review there is no reliable evidence that
homeopathy is more effective than placebo for the treatment of people with human
immunodeficiency virus.
Table 17 Evidence summary table: the effectiveness of homeopathy for the treatment of HIV
Study ID Included study Patient population Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Mills et al Rastogi (1999) HIV-positive patients, Homeopathy – not Placebo CD4 cell Significant difference in cell count There is no good-quality
(2005) [Level II] including 71 men and specific count before and after treatment in the PGL evidence to support the
[Level I] Poor quality 29 women. Age range group. No change in placebo and use of homeopathy in
AMSTAR: 8/10 N=100 18-50 years asymptomatic HIV group the HIV community.
Struwe (1993) HIV-positive patients, Dronabinol (delta-9- Placebo Body fat Significantly increase body fat (1%,
SR of CAM for
[Level II] mean age 38.0 tetrahydrocannabinol) p=0.04) in the treatment group
HIV
Poor quality (SD=7.3) compared with the control group
N=12
Symptom Significantly decreased symptom stress
distress (p=0.04) in the treatment group
compared with the control group
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; CAM, complementary and alternative medicines; HIV, human immunodeficiency virus; PGL, persistent generalised
lymphadenopathy; SD, standard deviation; SR, systematic review.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
Table 18 Matrix indicating the studies that were included in the systematic reviews of influenza or influenza-like illness
Systematic reviews
Mathie et al (2012) Bellavite et al (2011) Cucherat et al (2000)
[Level I] [Level I] [Level I]
Papp et al (1998)
[Level II]
Ferley et al (1989)
Study IDs
[Level II]
Casanova et al (1984)
[Level II]
Mathie et al (2012) (AMSTAR score 9/11) undertook a Cochrane review of homeopathic Anas
barbariae 200k (Oscillococcinum®) for influenza-like illness. The review provided an update of earlier
work completed by Vickers and Smith (2006). Four Level II studies (Casanova and Gerard, 1988;
Casanova et al, 1984; Ferley et al, 1989; Papp et al, 1998) were identified and included in the review,
all of which treated patients with various regimens of homeopathic Anas barbariae or placebo. The
studies reported efficacy based on a wide array of outcomes, including the presence of fever, cough,
spinal pain, muscle pain, headache, and fitness for work at various time points. Mathie et al (2012)
reported differences between the treatment arms using relative risks or mean differences, where
appropriate. In the study reported by Papp et al (1998), the relative risk significantly favoured
homeopathy according to “no spinal pain at 48 hours” (p=0.030); “no muscle pain at 48 hours”
(p=0.010); “no articular pain at 48 hours” (p=0.0090); and “use of concomitant medication during the
trial” (p=0.020). Significant inter-group differences were not reported for any other outcomes
(measures of headache, backache, physician-assessed symptoms and fitness for work).
An earlier study by Ferley et al (1989) also examined the efficacy of homeopathic Anas barbariae
compared to placebo. No significant inter-group differences were found for medications used for
cough or coryza and the prevalence of antibiotic use; however, the relative risk estimates
significantly favoured homeopathy based on “absence of symptoms at 48 hours”, stratified by
patient age (RR 1.98; 95% confidence interval (CI) 1.14, 3.43) and symptom severity (RR 1.65; 95% CI
1.02, 2.65). Similarly, the relative risk estimate significantly favoured homeopathy in terms of
medication used for pain or fever (p=0.048).
Mathie et al (2012) only reported one outcome from the Level II study conducted by Casanova and
Gerard (1988). The mean difference between the homeopathic Anas barbariae and placebo groups
on that outcome (temperature at 48 hours) significantly favoured homeopathy (p<0.00001).
Similarly, the majority of results reported in the study by Casanova et al (1984) significantly favoured
homeopathic Anas barbariae: “no fever at 48 hours” (p=0.00061), “no general aches at 48 hours”
(p=0.0072), and “no day cough at 48 hours” (p=0.0076). No significant difference was found between
the treatment groups based on night cough at 48 hours.
Mathie et al (2012) conducted a meta-analysis in which the results of the individual trials were
pooled (Table 20). Pooled estimates that included data from at least two Level II studies were
provided for five outcomes: patient-assessed absence of symptoms at 48 hours; no chills at 48 hours;
patient-assessed absence of symptoms at 3 days; patient-assessed absence of symptoms at 4 days;
and patient-assessed absence of symptoms at 5 days. Significant differences between homeopathic
Anas barbariae and placebo were found on three of the outcomes, two of which had no significant
heterogeneity between the included trials (patient-assessed absence of symptoms at 48 hours,
p=0.0014; patient-assessed absence of symptoms at 3 days, p=0.020). Based on the individual study
results and the results of the meta-analyses, Mathie et al (2012) concluded that there is “insufficient
good evidence to enable robust conclusions” about the efficacy of homeopathic Anas barbariae in
the treatment of influenza and influenza-like illness. In addition, the authors stated that the results
do not preclude the possibility of a clinical effect; however, they concluded that the evidence for the
efficacy of homeopathic Anas barbariae is not compelling, based on the low quality of the included
studies.
Bellavite et al (2011) (AMSTAR score 5/10) conducted a broad review of recent advances in
homeopathy and immunology across a range of clinical areas. Three studies (all discussed above)
were identified and included in the review: Casanova and Gerard (1988), Ferley et al (1989) and Papp
et al (1998). The authors of the systematic review did not provide results that were specific to each
of the outcomes assessed in the trials (as presented by Mathie et al, 2012) and did not provide p-
values to support claims of significance. However, the overall conclusion made by Bellavite et al
(2011) was that there was “good positive evidence” from three Level II studies for the use of Anas
barbariae 200K in the treatment of patients with influenza-like symptoms.
Cucherat et al (2000) (AMSTAR score 10/11) aimed to answer the question of “whether there is any
evidence from randomised controlled trials that homeopathy is efficacious for the treatment of
disease in humans”. The review included two Level II studies (Papp et al, 1998; Ferley et al, 1989),
and reported “significant differences” between the treatment arms in favour of the homeopathy
groups over placebo in both trials. Cucherat et al (2000) only reported one outcome for the study by
Papp et al (1998) which was a single variable of “rate of patients affected and duration of disease”;
however, as the way in which those outcomes were combined into one measure was not clear, the
validity of the results are questionable. Although the authors of the systematic review did not
provide a conclusion that was specific to homeopathy in influenza patients, they did conclude that
overall, across the clinical conditions, there is “insufficient evidence to conclude that homeopathy is
clinically effective” due to the low methodological quality of the included trials.
Reviewer comments
The systematic review by Mathie et al (2012) did not provide overall quality assessment scores for the
included studies, yet measures of internal validity were assessed and documented. Two of the
included studies (Casanova et al 1984; Casanova and Gerard 1988) had an “unclear risk of bias” due
to the fact that details relating to allocation concealment, random sequence generation, and blinding
of participants and outcome assessors were not reported. In addition, the reporting of outcome data
was not complete in either of the studies.
Similarly, Ferley et al (1989) did not provide any details about random sequence generation,
allocation concealment or blinding. Papp et al (1998) did provide information regarding
randomisation, allocation concealment and blinding of participants and was deemed to have a low
risk of bias on those measures. However, the risk of bias was unclear for the blinding of outcome
assessment and the reporting of outcome data was incomplete.
As a result, the evidence reviewer supports the conclusion by Mathie et al (2012) that the evidence for
the efficacy of homeopathic Anas barbariae is not compelling based on the low quality of the included
studies.
Evidence statement
Three systematic reviews of poor to good quality identified four randomised controlled trials (quality
not reported; total of 1259 participants, range: 100-487) that compared homeopathy (Anas
barbariae) with placebo for the treatment of people with influenza-like illness.
These studies are of insufficient quality and/or size to warrant further consideration of their findings.
LOC: Low.
Based on the body of evidence evaluated in this review there is no reliable evidence that
homeopathy is more effective than placebo for the treatment of people with influenza-like illness.
Table 19 Evidence summary table: the effectiveness of homeopathy for the treatment of influenza-like illness
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Mathie et al Papp et al (1998) Patients in Oscillococcinum® Placebo Fitness for work at 2 No significant difference “There is insufficient good
(2012) [Level II] primary care 3 times a day for days (RR 1.80; 95% CI 0.99-3.26) evidence to enable robust
[Level I] Quality score not with influenza- 3 days conclusions to be made
like symptoms Fitness for work at 4 No significant difference about Oscillococcinum in
AMSTAR: 9/11 reported
mean age 35 days (RR 1.04; 95% CI 0.83-1.30) the treatment of influenza
N=372
years and influenza-like illness.
SR of No headache at 48 No significant difference
homeopathy Our findings do not rule out
hours (RR 1.20; 95% CI 0.88-1.63)
for influenza the possibility that
No backache at 48 No significant difference Oscillococcinum could have
hours (RR 1.27; 95% CI 1.00-1.61; a clinically useful treatment
p=0.05) effect but, given the low
quality of the eligible
No spinal pain at 48 Favours homeopathy (RR 1.27; studies, the evidence is not
hours 95% CI 1.02-1.58; p=0.030) compelling. There was no
evidence of clinically
No muscle pain at 48 Favours homeopathy (RR 1.47; important harms due to
hours 95% CI 1.10-1.97; p=0.010) Oscillococcinum.”
No articular pain at 48 Favours homeopathy (RR 1.40;
hours 95% CI 1.09-1.80; p=0.0090)
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Ferley et al Participants in Oscillococcinum® Placebo Absence of symptoms Favours homeopathy (RR 1.98;
(1989) primary care twice a day for 5 at 48 hours – patient 95% CI 1.14-3.43; p-value not
[Level II] with a complaint days assessment by age reported)
Quality score not of influenza-like (12-29 yr; 30+ yr)
reported illness
aged 12 years or
Absence of symptoms Favours homeopathy (RR 1.65;
N=487 at 48 hours – patient 95% CI 1.02-2.65; p-value not
older (mean age
approx. 34 years) assessment by reported)
rectal severity of symptoms
temperature (severe; mod to
above 38°C severe)
Casanova et al Patients with Oscillococcinum®, Placebo No fever at 48 hours Favours homeopathy (RR 1.98;
(1984) influenza-like 4 doses in over 2 95% CI 1.34-2.92; p=0.00061)
[Level II] illness days at 6-hour
No rhinitis at 48 hours No significant difference
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Quality score not onset <48 hours intervals (RR 1.33; 95% CI 0.66-2.70)
reported previously
N=100 average age No general aches at 48 Favours homeopathy (RR 1.73;
approx. 42 years hours 95% CI 1.16-2.59; p=0.0072)
Bellavite et al Papp et al (1998) Patients with Oscillococcinum NR Evaluation of Statistically significant There is “good positive
(2011) [Level II] influenza-like (Anas barbariae symptoms after reduction of symptoms after 48 evidence” from three Level
[Level I] Quality score not symptoms 200k) 1 dose, 3 treatment hours in the homeopathy group II studies for the use of Anas
AMSTAR: 5/10 reported times per day for barbariae 200K in the
N=372 3 days treatment of influenza-like
SR of symptoms
Ferley et al Patients with Oscillococcinum NR Healing rate at 48 Clinical healing after 48 hours
homeopathy
(1989) influenza-like (Anas barbariae hours after diagnosis and rate of temperature
for multiple
[Level II] symptoms 200k) 5 doses, based on rectal reduction better in the
conditions
Quality score not one every 12 temperature and two homeopathy group
reported hours of the following:
N=487 headache, stiffness,
lumbar pain, articular
ache, shivering
Cucherat et al Papp et al (1998) Patients with Oscillococcinum Placebo Multiple endpoint: Significant difference in favour “There is some evidence
(2000) [Level II] influenza-like rate of patients of homeopathy (p=0.0257) that homeopathic
affected and duration treatments are more
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
[Level I] Quality score not syndromes of disease effective than placebo;
d
AMSTAR: 10/11 reported however, the strength of
N=372 this evidence is low because
SR of of the low methodological
Ferley et al Patients with Fixed, Placebo Recovery rate within Significant difference in favour quality of the trials. Studies
homeopathy
(1989) influenza-like Oscillococcinum 48 hours of treatment of homeopathy (p=0.032) of high methodological
for multiple
[Level II] syndromes quality were more likely to
conditions
Quality score not be negative than the lower
d
reported quality studies. Further high
N=487 quality studies are needed
to confirm these results.”
Absence of symptoms at 48 hours – patient assessment 66/395 (16.7) 36/401 (9.0) 1.86 (1.27-2.73) Favours homeopathy (p=0.0014)
(2 Level II studies; N=796) No significant heterogeneity
2
Ferley 1989 (p=0.46; I =0%)
Papp 1998
No chills at 48 hours 136/209 (65.1) 108/209 (51.7) 1.30 (1.04-1.63) Favours homeopathy (p=0.020)
(2 Level II studies; N=418) Moderate heterogeneity
2
Casanova 1984 (p=0.19; I =42%)
Papp 1998
Absence of symptoms at 3 days (patient’s assessment) 136/395 (34.4) 109/401 (27.2) 1.27 (1.03-1.56) Favours homeopathy (p=0.020)
(2 Level II studies; N=796) No significant heterogeneity
2
Ferley 1989 (p=0.94; I =0%)
Papp 1998
Absence of symptoms at 4 days (patient’s assessment) 223/395 (56.5) 203/401 (50.6) 1.11 (0.98-1.27) No significant difference (p=0.10)
(2 Level II studies; N=796) No significant heterogeneity
2
Ferley 1989 (p=0.88; I =0%)
Papp 1988
Absence of symptoms at 5 days (patient’s assessment) 277/395 (70.1) 266/401 (66.3) 1.06 (0.96-1.16) No significant difference (p=0.25)
(2 Level II studies; N=796) No significant heterogeneity
2
Ferley 1989 (p=0.94; I =0%)
Papp 1988
Abbreviations: CI, confidence interval; RR, relative risk.
a 2 2 2
Heterogeneity defined as follows: (i) no significant heterogeneity if Phet>0.1 and I <25%; (ii) mild heterogeneity if I <25%; moderate heterogeneity if I between 25-50%; substantial
2
heterogeneity I >50%.
4.7.5 Malaria
The effectiveness of homeopathy for the treatment of malaria was assessed in one systematic review
(Linde and Melchart, 1998) (AMSTAR score 8/11) as summarised in Table 21. Linde and Melchart
(1998) examined the efficacy of homeopathy in a number of chronic conditions and infectious
diseases, and identified one Level II study (Jadad score of 2) that specifically examined homeopathy
as a treatment for malaria (van Erp and Brands, 1996). Van Erp and Brands (1996) compared the
number of patients assessed as “globally improved” between those treated with chloroquine and
those treated with individualised homeopathic simillimum. No Level II, Level III-1 or Level III-2
studies were identified that compared homeopathy to placebo for the treatment of malaria. In Van
Erp and Brands (1996), a similar improvement was reported in the homeopathy and chloroquine
groups (83% and 72% of patients, respectively); the statistical significance of the result was not
reported. Linde and Melchart (1998) concluded that the result “seemed promising”; however the
study was excluded from their meta-analysis due to methodological flaws, including “insufficient
description of outcome measurement”.
Evidence statement
One systematic review (1998) did not identify any prospectively designed and controlled studies that
assessed the effectiveness of homeopathy compared with placebo for the treatment of people with
malaria.
One systematic review of medium quality identified one small randomised controlled trial (poor
quality; 74 participants) that compared homeopathy (Simillimum) with chloroquine for the treatment
of people with malaria. LOC: Very low.
Based on only one small poor quality study there is no reliable evidence on which to draw a
conclusion about the effectiveness of homeopathy compared to chloroquine for the treatment of
people with malaria.
Table 21 Evidence summary table: the effectiveness of homeopathy for the treatment of malaria
Study ID Included study Patient Intervention Comparator Outcome Results as reported Systematic review interpretation
Level of Level of population in the systematic
a a
evidence evidence review
b c
Quality Quality
Sample size
Linde and van Erp and Patients with Individual Chloroquine Number of Similar response in Comments about the included Level II study:
Melchart (1998) Brands (1996) malaria attack simillimum patients both groups. “The trial of van Erp and Brands (1996) on malaria
[Level I] [Level II] (57% female) assessed Intervention group: seems promising, but the reporting in the study is
d
AMSTAR: 8/11 Jadad score 2 globally as 25/30 (83%); Control inadequate.”
N=74 improved group: 18/25 (72%).
SR of Conclusions of the systematic review:
homeopathy for Significance of inter- A meta-analysis found an overall trend in favour of
multiple group differences not homeopathy.
conditions reported The rate ratio was 1.62 (95% CI 1.17 to 2.23) and
the odds ratio was 2.62
The pooled rate ratio of the methodologically best
studies was clearly smaller and not statistically
significant (1.12, 95% CI 0.87, 1.44)
The rate ratio of the six studies published in
MEDLINE-listed journals was not significantly
different from placebo (1.22, 95% CI 0.94, 1.56)
Evidence statement
One systematic review (2011) did not identify any prospectively designed and controlled studies that
assessed the effectiveness of homeopathy compared with placebo for the treatment of women with
recurrent vulvovaginal candidiasis.
One systematic review of medium quality identified one medium-sized randomised controlled trial
(quality not reported; 150 participants) that compared homeopathy with itraconazole for the
treatment of women with recurrent vulvovaginal candidiasis. LOC: Low.
Based on only one study of unknown quality there is no reliable evidence on which to draw a
conclusion about the effectiveness of homeopathy compared to itraconazole for the treatment of
women with recurrent vulvovaginal candidiasis.
Table 22 Evidence summary table: the effectiveness of homeopathy for the treatment of recurrent vulvovaginal candidiasis
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review interpretation
a
Level of Level of evidence population systematic review
a c
evidence Quality
b
Quality Sample size
Simonart et al, Witt et al, 2009 Women with Individually Conventional Culture-free Conventional therapy group “The hypothesis that any
2011 [Level II] recurrent selected therapy status reached a culture-free status dermatological condition responds
[Level I] Quality not specified vulvovaginal homeopathic (itraconazole) significantly earlier than convincingly better to homeopathic
AMSTAR: 8/10 N=150 candidiasis remedies for homeopathy group (p<0.0001) treatment than to placebo or other
12 months 9/23 in homeopathy group and 18/23 control interventions is not supported
in conventional therapy group by evidence.”
SR of homeopathy
for multiple Level of Significantly lower level of
conditions discomfort discomfort in conventional (Note: this conclusion refers to all
therapy group (p<0.001) clinical conditions and is not specific
VAS score 36.8 in homeopathy group to recurrent vulvovaginal candidiasis)
and 25.1 in conventional therapy
group
Evidence statement
One systematic review of good quality identified one small randomised controlled trial (quality not
reported; 69 participants) that compared homeopathy (Traumeel) with placebo for the treatment of
people with acute ankle sprains. LOC: Very low.
Based on only one small study of unknown quality there is no reliable evidence on which to draw a
conclusion about the effectiveness of homeopathy compared to placebo for the treatment of people
with acute ankle sprains.
Table 23 Evidence summary table: the effectiveness of homeopathy for the treatment of acute ankle sprains
Study ID Included study Patient Intervention Comparator Outcome Results as reported Systematic review
Level of Level of population in the systematic interpretation
a a
evidence evidence review
b c
Quality Quality
Sample size
Cucherat et al Zell (1988) Patients with Traumeel Ointment base Composite criteria Significant difference “It is clear that the strength of
(2000) [Level II] acute ankle ointment without active of treatment in favour of available evidence is insufficient
[Level I] Quality not sprains constituent success homeopathy to conclude that homeopathy is
AMSTAR: 10/11 specified (p=0.028) clinically effective.”
d
N=69
SR of (Note: this conclusion refers to all
homeopathy for clinical conditions and is not
multiple specific to ankle sprains)
conditions
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; SR, systematic review.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
d
Number of participants refers to the number who were evaluated. The number randomised was not reported.
Reviewer comments
A major flaw of the systematic review by Ernst and Pittler (1998) was poor reporting; however, it was
unclear whether the authors of the included trial poorly-reported their findings, or whether the results
were poorly conveyed by the systematic review authors. For example, Ernst and Pittler (1998)
indicated that there were “no significant differences” across the four outcomes, although it was
unclear whether the significance was referring to differences between treatment arms (homeopathy
versus placebo), or within treatment arms (from baseline to follow-up). Based on the author’s overall
conclusions it was assumed that the lack of significance referred to a lack of inter-group differences.
Interpretation of the results by the evidence reviewer was also limited by the fact that the systematic
review authors did not present any numerical data or p-values to support their conclusions about
homeopathy and acute trauma. Again, it was unclear to the evidence reviewer whether the numerical
values were omitted from the systematic review, or not available in the included studies.
Evidence statement
One systematic review of medium quality identified one very small prospectively designed, non-
randomised controlled study (poor quality; 20 participants) that compared homeopathy (Arnica) with
placebo for the treatment of people with acute trauma. LOC: Very low.
Based on only one very small poor quality study is no reliable evidence on which to draw a conclusion
about the effectiveness of homeopathy compared to placebo for the treatment of people with acute
trauma.
Table 24 Evidence summary table: the effectiveness of homeopathy for the treatment of acute trauma
Study ID Included study Patient Intervention Comparator Outcome Results as reported in Systematic review
Level of Level of population the systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Ernst and Pittler Gibson et al Orthopaedic Arnica 30. Placebo Pulse rate No significant difference “The hypothesis claiming that
(1998) (1991) patients for the Frequency and dose homeopathic Arnica is clinically
[Level III-2] treatment of of medication not Blood pressure No significant difference effective beyond a placebo
[Level I/III]
d
AMSTAR: 6/10 Jadad score 2 acute trauma stated. Respiratory rate No significant difference effect is not based on
N=20 methodologically sound
SR of Subjective symptoms No significant difference placebo-controlled trials.”
homeopathy for
multiple (Note: this conclusion refers to
conditions all clinical conditions and is not
specific to acute trauma)
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; SR, systematic review.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
d
The Jadad scale assesses the quality of published clinical trials based methods relevant to random assignment, double blinding and the flow of patients. The range of possible scores is zero
(bad quality) to 5 (good quality).
Evidence statement
Two systematic reviews of medium quality identified one small randomised controlled trial (good
quality; 61 participants) that compared homeopathy with placebo for the treatment of people with
mild traumatic brain injury. LOC: Low.
Based on only one small study there is no reliable evidence on which to draw a conclusion about the
effectiveness of homeopathy compared to placebo for the treatment of people with mild traumatic
brain injury.
Table 25 Evidence summary table: the effectiveness of homeopathy for the treatment of mild traumatic brain injury
Study ID Included study Patient Intervention Comparator Outcome Results as reported in Systematic review
a
Level of Level of evidence population the systematic review interpretation
a c
evidence Quality
b
Quality Sample size
Davidson et al Chapman et al Patients with Individualised Placebo Multivariate analysis of Significant improvement Weakly positive results in
(2011) (1999) mild traumatic homeopathy variance for functional favouring homeopathy favour of homeopathy for
[Level I] [Level II] brain injury assessment (p=NR) mild traumatic brain injury
AMSTAR: 8/10 Good quality
d
N=61
SR of
homeopathy for
multiple
conditions
Linde and Chapman et al Patients with Best-fitting from Placebo Unclear “Homeopathy significantly No overall conclusions were
e
Melchart (1998) (1997) mild traumatic 18 predefined superior” provided about the efficacy
[Level I] [Level II] brain injury homeopathic of homeopathy in patients
f remedies with mild traumatic brain
AMSTAR: 8/11 Quality not assessed
N=50 injury
SR of
homeopathy for
multiple
conditions
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; NR, not reported; SR, systematic review.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
d
50 participants completed the study.
e
Chapman et al (1997) is an abstract and refers to the same study that was later reported in Chapman et al (1999) and included in the systematic review by Davidson et al (2011).
f
The quality of the study was not assessed, as it was available as an abstract only.
Evidence statement
Two systematic reviews of medium to good quality identified one small randomised controlled trial
(poor quality; 50 participants) that compared homeopathy (Aconite) with placebo for the treatment
of people with postoperative pain-agitation syndrome. LOC: Very low.
Based on only one small poor quality study there is no reliable evidence on which to draw a
conclusion about the effectiveness of homeopathy compared to placebo for the treatment of people
with postoperative pain-agitation syndrome.
Table 26 Evidence summary table: the effectiveness of homeopathy for the treatment of postoperative pain-agitation syndrome
Study ID Included study Patient population Intervention Comparator Outcome Results as reported Systematic review
Level of Level of in the systematic interpretation
a a
evidence evidence review
b c
Quality Quality
Sample size
Altunc et al Alibeu and Jobert Patients with Aconite, dose not reported, Placebo Sedation of Significant difference “The evidence from rigorous
(2007) (1990) postoperative pain- administered at least once, agitation (within (p<0.05) clinical trials of any type of
[Level I] [Level II] agitation syndrome to be repeated as many 15 minutes of therapeutic or preventive
AMSTAR: 6/10 Jadad score 2
d Mean age 6 months-14 times as necessary operation) intervention testing
N=50 years homeopathy for childhood
72% male and adolescence ailments is
SR of
Concomitant treatment: not convincing enough for
homeopathy Halothane (1.5%), nitric
for multiple recommendations in any
oxide, Alimemazine (1
conditions condition.”
mg/kg), methohexital (25
mg/kg intrarectally)
(Note: this conclusion refers
to all clinical conditions and
is not specific to
postoperative pain-agitation
syndrome)
Cucherat et al Alibeu and Jobert Patients with Aconite 4 °C Placebo Sedation of Significant difference “It is clear that the strength
(2000) (1990) postoperative pain- agitation (within in favour of of available evidence is
[Level I] [Level II] agitation syndrome 15 minutes of homeopathy insufficient to conclude that
AMSTAR: Quality not operation) (p=0.002) homeopathy is clinically
10/11 specified effective.”
N=50
SR of (Note: this conclusion refers
homeopathy to all clinical conditions and
for multiple is not specific to
conditions postoperative pain-agitation
syndrome)
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; C, centesimal; SR, systematic review.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
d
The Jadad scale assesses the quality of published clinical trials based methods relevant to random assignment, double blinding and the flow of patients. The range of possible scores is zero
(bad quality) to 5 (good quality).
Evidence statement
One systematic review of poor quality identified one small randomised controlled trial (quality not
reported; 104 participants) that compared homeopathy (Formica rufa) with placebo for the
treatment of people with ankylosing spondylitis. LOC: Very low.
Based on only one small study of unknown quality there is no reliable evidence on which to draw a
conclusion about the effectiveness of homeopathy compared to placebo for the treatment of people
with ankylosing spondylitis.
Table 27 Evidence summary table: the effectiveness of homeopathy for the treatment of ankylosing spondylitis
Study ID Included study Patient Intervention Comparator Outcome Results as reported Systematic review
Level of Level of population in the systematic interpretation
a a
evidence evidence review
b c
Quality Quality
Sample size
Bellavite et al Schirmer et al Patients with Intramuscular Placebo (injection Questionnaire on No difference There is “negative scientific
(2011) (2000) ankylosing treatment with a of saline) arthritis and general compared to placebo evidence” (i.e. lack of
[Level I] [Level II] spondylitis combination of low physician assessment evidence of benefit)
AMSTAR: 5/10 Quality result not homeopathic regarding the efficacy of
reported potencies of Formica rufa 6X in patients
SR of N=104 Formica rufa and with ankylosing spondylitis
homeopathy the patient’s own
for multiple blood
conditions
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; SR, systematic review.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
Reviewer comments
The evidence reviewer cannot comment on the quality of the one included Level II study, as it was not
formally assessed by Bellavite et al (2011). It was also unclear to the evidence reviewer how the
individual outcomes were combined into a single outcome variable and whether the grouping of
outcomes into a single measure was the intention of Wiesenauer and Gaus (1991) at the beginning of
the study or whether it was a post-hoc analysis.
It was assumed from the results provided by Bellavite et al (2011) that the “significant efficacy” of the
combined measure in the homeopathy group referred to a significant difference over the placebo
group, rather than a change from baseline; however, this was unclear from the poor wording of the
results.
Evidence statement
One systematic review of poor quality identified one small randomised controlled trial (quality not
reported; 111 participants) that compared homeopathy (Rheumaselect) with placebo for the
treatment of people with chronic polyarthritis. LOC: Very low.
Based on only one small study of unknown quality there is no reliable evidence on which to draw a
conclusion about the effectiveness of homeopathy compared to placebo for the treatment of people
with chronic polyarthritis.
Table 28 Evidence summary table: the effectiveness of homeopathy for the treatment of chronic polyarthritis
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic
Level of Level of population systematic review review
a a
evidence evidence interpretation
b c
Quality Quality
Sample size
Bellavite et al Wiesenauer and Patients with Homeopathic Placebo Inflammation markers, A remarkable improvement in Overall slightly
(2011) Gaus (1991) chronic preparation functional indexes, use symptoms was reported for both better outcomes in
d
[Level I] [Level II] polyarthritis Rheumaselect of ‘standard’ drugs, groups. However, when the homeopathy
AMSTAR: 5/10 Quality result not general assessment consumption of antirheumatic and group
reported analgesic drugs and the assessment
SR of N=111 of pain by the patient were
homeopathy for combined into a single outcome
multiple variable, the result was a significant
conditions efficacy of the homeopathic
remedy.
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; SR, systematic review.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
d
A mixture of low potencies of Rhus toxicodendron, Bryonia, Nux vomica, Berberis, Ledum
Table 29 Matrix indicating the studies that were included in the systematic reviews of delayed-onset muscle soreness
Systematic review
Ernst and Barnes (1998) Ernst and Pittler (1998)
[Level I/III] [Level I/III]
Jarawa et al (1997)
[Level II]
Vickers et al (1997)
[Level II]
Tveiten et al (1991)
[Level II]
Hildebrandt and Eltze (1984)
Study ID
[Level III-2)
Hildebrandt and Eltze (1983a)
[Level III-2)
Hildebrandt and Eltze (1983b)
[Level III-2)
Hildebrandt and Eltze (1983c)
[Level III-2)
Hildebrandt and Eltze (1983d)
[Level III-2)
Ernst and Barnes (1998) (AMSTAR score 7/10) conducted a systematic review aimed at comparing
the efficacy of homeopathy to placebo in DOMS. Three Level II studies were identified that examined
DOMS in healthy volunteers (Jawara et al, 1997; Tveiten et al, 1991; Vickers et al, 1997). None of the
trials reported a significant difference in soreness intensity or mean muscle soreness after exercise
between the homeopathy and placebo groups. In terms of the timing or duration of soreness,
Tveiten et al (1991) reported no significant difference in soreness duration between the treatment
groups, and Vickers et al (1997) reported no significant inter-group differences based on “symptom
free days”, “days to no soreness” and “days of no medication”.
The systematic review also included five Level III-2 studies (Hildebrandt and Eltze 1983a; Hildebrandt
and Eltze 1983b; Hildebrandt and Eltze 1983c; Hildebrandt and Eltze 1983d; Hildebrandt and Eltze,
1984) that examined a variety of strengths and dosing regimens of Rhus toxicodendron or Arnica on
DOMS in female participants. All five studies measured DOMS in the participants’ arms and reported
a smaller decrease in muscle strength in at least one of the homeopathic regimens compared to
placebo; however the statistical significance of the findings were not reported. One study reported a
shorter duration of arm soreness (Hildebrandt and Eltze, 1984) and another reported less intense
soreness (Hildebrandt and Eltze 1983d) in at least one active treatment group, and in at least one
arm of the participant, compared with placebo. Again, the significance of the findings is not clear due
to the fact that p-values were not provided. As it is likely that any statistically significant findings
would have been clearly identified, it is assumed that no statistically significant inter-group
differences were achieved.
Overall, Ernst and Barnes (1998) reported that the “partly positive findings” in favour of homeopathy
were all from Level III-2 studies that had a high risk of bias. They concluded that there was “no
convincing evidence that the homeopathic remedies tested are more than placebos”.
Ernst and Pittler (1998) (AMSTAR score 6/10) performed a broad review of homeopathic Arnica and
included the DOMS studies by Tveiten et al (1991; Level II) and Hildebrandt and Eltze (1984; Level III-
2). No additional results were reported, and the systematic review authors concluded overall that
there is no evidence based on “methodologically sound placebo-controlled trials” that Arnica has any
clinical effect beyond that of placebo.
Reviewer comments
A major limitation of the evidence base for DOMS was low recruitment/small studies. For example,
Jawara et al (1997) calculated that a sample size of 170 would be needed to have 80% power at a 5%
level of significance; however, the study only included 36 participants.
A meta-analysis is often conducted as a means of overcoming small sample sizes and underpowered
studies; however it would have been inappropriate in this instance given the highly heterogeneous
trials. In particular, a wide variety of homeopathic remedies were used and there were also significant
differences between the trials in terms of the type and extent of exercise used to induce DOMS (for
example, bilateral upper arm muscle flexion and extension; bench-stepping exercise; or running a
marathon).
Evidence statement
Two systematic reviews of medium quality identified three randomised controlled trials (medium to
good quality; total of 143 participants, range: 36-57) and five prospectively designed, non-
randomised controlled studies (poor quality; total of 172 participants, range: 24-44) that compared
homeopathy with placebo for the treatment of people with delayed onset muscle soreness. The five
non-randomised controlled studies were conducted by the same research group. LOC: Low.
Based on the body of evidence evaluated in this review homeopathy is not more effective than
placebo for the treatment of people with delayed-onset muscle soreness.
Table 30 Evidence summary table: the effectiveness of homeopathy for the treatment of delayed-onset muscle soreness
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the systematic Systematic
Level of Level of population review review
a a
evidence evidence interpretation
b c
Quality Quality
Sample size
Ernst and Jawara et al (1997) Oslo Arnica Montana D30, Placebo Soreness intensity No significant inter-group differences, but a “The partly
Barnes (1998) [Level II] Marathon 5 pills twice daily for (VAS) trend for less soreness in homeopathy positive findings
d
[Level I/III] Quality score 85 participants 5 days starting 1 day compared with placebo group in favour of
AMSTAR: 7/10 N=36 with delayed- prior to the Oslo homeopathy…
onset muscle Marathon Serum CK No significant inter-group differences, but a are based on
soreness concentrations trend for lower serum CK in homeopathy trials that were
SR of compared with placebo group
homeopathy for non-randomised
delayed-onset Vickers et al (1997) Healthy Arnica Montana 30C Placebo Mean muscle No significant inter-group differences, but a and thus are
muscle [Level II] volunteers + Rhus toxicodendron soreness (during the trend for less soreness in placebo compared open to bias, and
soreness d with delayed- 30C + sarcolactic acid 5 post-exercise days) with the homeopathy group which involve
Quality score 85
onset muscle 30C, one tablet three small numbers of
N=57 Symptom free days No significant inter-group differences
soreness times daily, one day patients.”
prior to exercise until Maximum soreness No significant inter-group differences
cessation of soreness “The results of all
score
eight clinical
Days to no soreness No significant inter-group differences trials of
homeopathy for
Days of no No significant inter-group differences delayed-onset
medication muscle soreness
Tveiten et al (1991) Healthy Arnica montana 30C Placebo Soreness intensity Intergroup differences did not approach do not provide
volunteers + Rhus toxicodendron (VAS) statistical significance (p>0.2), but trend convincing
[Level II]
d with delayed- 30C one tablet three favoured homeopathy evidence that
Quality score 60 the homeopathic
N=50 onset muscle times daily one day
soreness prior to exercise Soreness duration Intergroup differences did not approach remedies tested
statistical significance (p>0.2), but trend are more than
continuing until
cessation of soreness favoured homeopathy placebos.”
Hildebrandt and Healthy Arnica (a) D2 (b) D3 Placebo Soreness intensity No significant inter-group differences
Eltze (1984) women with (c) D4 (d) D5 (e) D6 (f)
delayed- D8, 3x16 drops daily Soreness duration Shorter duration in homeopathic group (b)
[Level III-2]
d onset muscle for 6 days post compared with placebo (both arms) and in
Quality score 38
group (c) compared with placebo (left arm
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the systematic Systematic
Level of Level of population review review
a a
evidence evidence interpretation
b c
Quality Quality
Sample size
N=42 soreness exercise only); p-values NR
Serum CK NR
concentrations
Hildebrandt and Healthy Rhus toxicodendron Placebo Soreness intensity No significant inter-group differences
Eltze (1983a) women with D4, 5x10 drops daily
delayed- for 7 days post Soreness duration No significant inter-group differences
[Level III-2]
d onset muscle exercise
Quality score 38 Maximal isometric Less decrease in muscle strength in
N=28 soreness muscle strength homeopathy group vs placebo; p-value NR
Hildebrandt and Healthy Rhus toxicodendron Placebo Soreness intensity No significant inter-group differences
Eltze (1983c) women with D4 (a) 1x5 drops
delayed- daily, (b) 3x5 drops Soreness duration No significant inter-group differences
[Level III-2]
d onset muscle daily, (c) 5x10 drops
Quality score 38 Maximal isometric Less decrease in muscle strength in
N=24 soreness daily, for 7 days post muscle strength homeopathic groups (b) and (c) vs placebo
exercise (right arm only); p-value NR
Hildebrandt and Healthy Rhus toxicodendron Placebo Soreness intensity Less soreness in homeopathic group (c) vs
Eltze (1983d) women with (a) D2 (b) D3 (c) D4 placebo (both arms); p-value NR
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the systematic Systematic
Level of Level of population review review
a a
evidence evidence interpretation
b c
Quality Quality
Sample size
[Level III-2] delayed- (d) D5 (e) D6 (f) D8, Soreness duration NR
d
Quality score 38 onset muscle 3x16 drops daily for 7
N=44 soreness days post exercise
Ernst and Pittler Tveiten et al (1991) Participants Arnica montana D30 Placebo pills Blood tests, “No significant intergroup differences but a “The hypothesis
(1998) [Level II] in the Oslo 5 pills twice daily for as per verum including serum trend for serum creatine kinase claiming that
e Marathon 5 days starting 1 day schedule creatine kinase concentrations to be lower with Arnica than homeopathic
[Level I] Jadad score 4
AMSTAR: 6/10 N=36 (Norway) prior to race concentrations placebo” Arnica is clinically
effective beyond
Soreness intensity “No significant intergroup differences but a a placebo effect
SR of (VAS) trend for soreness to be lower with Arnica
homeopathy for is not based on
than placebo” methodologically
multiple
conditions Soreness duration No significant difference sound placebo-
controlled trials.”
Hildebrandt and Healthy Arnica D2, D3, D4, D5, Placebo Maximal isometric “Less decrease in muscle strength in group B
e
Eltze (1984) women for D6, D8 - 16 drops, 3 drops as per muscle strength vs placebo (both arms)” (Note: this
[Level III-2] the times a day for 6 days verum conclusion refers
e treatment of after exercise schedule Soreness intensity No significant difference
Jadad score 1 to all clinical
N=42 delayed- Soreness duration “Shorter duration of soreness in group B conditions and is
onset muscle (both arms) and C (left arm only) vs not specific to
soreness placebo”
f,g delayed-onset
muscle soreness)
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; C, centesimal; CK, creatinine kinase; D, decimal; NR, not reported; SR, systematic review; VAS, visual analogue scale.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
d
Quality was assessed using a “pre-defined list of criteria” (further details not specified) in which a score of ≥55 indicates studies of “higher quality”.
e
The Jadad scale assesses the quality of published clinical trials based methods relevant to random assignment, double blinding and the flow of patients. The range of possible scores is zero
(bad quality) to 5 (good quality).
f
What constitutes groups B and C were not defined by the authors.
g
Lower creatinine kinase concentration on day 6 in group C vs placebo.
4.9.4 Fibromyalgia
The effectiveness of homeopathy in the treatment of fibromyalgia was assessed in seven systematic
reviews as summarised in Table 31 and Table 32. Overall, the systematic reviews included four Level
II studies (Bell et al, 2004; Fisher et al, 1989; Fisher, 1986; Relton et al, 2009). Two of the seven
reviews (Bellavite et al, 2011; Perry et al, 2010) reported results from all four Level II studies (see
Table 31). Perry et al (2010) provided the most comprehensive details of the individual study results.
Table 31 Matrix indicating the studies that were included in the systematic reviews of fibromyalgia
Study ID
Relton et al Bell et al Fisher et al Fisher
(2009) (2004) (1989) (1986)
[Level II] [Level II] [Level II] [Level II]
Bellavite et al (2011)
[Level I]
Davidson et al (2011)
[Level I]
de Silva et al (2010)
Systematic review
[Level I]
Perry et al (2010)
[Level I]
Porter et al (2010)
[Level I]
Baranowsky et al
(2009)
[Level I]
Holdcraft et al (2003)
[Level I]
Perry et al (2010) (AMSTAR score 8/10) conducted a systematic review that specifically examined the
efficacy of homeopathy in the treatment of fibromyalgia. Four Level II studies (Bell et al, 2004; Fisher
et al, 1989; Fisher, 1986; Relton et al, 2009) were identified, none of which were “without serious
flaws” (Perry et al, 2010). The two highest quality studies (Bell et al, 2004; Fisher et al, 1989) received
a Jadad score of 4 (Perry et al, 2010), and both reported significantly fewer tender points (or a
significantly greater improvement in tender point count) in the homeopathy group, compared to
placebo. In addition, Bell et al (2004) reported statistically significant differences in favour of
homeopathy in the following outcomes: number of patients with at least a 25% improvement in
tender point pain on palpation; Fibromyalgia Score; and Global Health Rating. Fisher et al (1989) (a
cross-over study) also reported that a significantly greater number of patients experienced improved
pain and sleep in the homeopathy group (Rhus toxicodendron) compared with placebo (p=0.0052).
However, Perry et al (2010) noted that a re-analysis of the data performed by Colquhoun (1990)
“suggested that there was no evidence for the efficacy of homeopathy treatment when distribution-
free-randomisation tests were employed”.
An earlier Level II study by Fisher (1986; Jadad score 3) examined the efficacy of three homeopathic
remedies compared to placebo. The main criticisms of the trial cited by Perry et al (2010) were that
the authors did not describe the randomisation process, presented very little demographic
information on the patients, conducted the trial over a short duration, and recruited very few
patients (≤5 patients in each of the three homeopathic treatment arms). No significant differences
were reported between the three homeopathy groups and the placebo group in terms of pain and
sleep; however, the results of both outcomes significantly favoured homeopathy when the authors
re-grouped patients into those who received “poorly-indicated” homeopathic remedies and those
that received “well-indicated” treatments.
Finally, Perry et al (2010) identified a poor-quality Level II study (Jadad score 2) by Relton et al (2009)
for inclusion in their systematic review. Relton et al (2009) adopted an individually tailored
homeopathic approach (i.e. where remedy choice and potency could be altered throughout the
study). The results indicated that those in the homeopathy group achieved a significantly greater
reduction in the total Fibromyalgia Impact Questionnaire score, compared to the “usual care” group
(p<0.01) which included patients treated with one or more of physiotherapy, aerobic exercise, anti-
inflammatory drugs, or anti-depressants. However, on all other outcomes (tender point count,
European Quality of Life Scale, Hospital Anxiety and Depression Scale, Measure Yourself Medical
Outcome Profile, and Fibromyalgia Impact Questionnaire – pain score), the study found no significant
inter-group differences. Perry et al (2010) highlighted the major limitations of the Level II study by
Relton et al (2009), including the utilisation of a study design that did not control for placebo effects
and a very small sample size due to a high dropout rate in the “usual care” treatment arm. Overall,
Perry et al (2010) concluded that the “effectiveness of homeopathy as a symptomatic treatment for
fibromyalgia remains unproven”, largely due to the limited number of Level II studies and the
relatively poor scientific quality of the existing trials.
The systematic review by Bellavite et al (2011) (AMSTAR score 5/10) aimed to evaluate the
effectiveness of homeopathy for the treatment of upper airways and ear-nose-throat ailments,
respiratory allergies, arthrorheumatic diseases and osteoarthritis. Based on the findings of three of
the included Level II studies (Bell et al, 2004; Fisher et al, 1989; Relton et al, 2009), Bellavite et al
(2011) concluded that there was “good positive evidence” for the effective treatment of fibromyalgia
with individualised homeopathy. Based on Fisher (1996), Bellavite et al (2011) concluded that there
was “negative scientific evidence” (i.e. lack of evidence of benefit) for homeopathic Arnica, Rhus
toxicodendron and Bryonia 6C for the treatment of fibromyalgia. Bellavite et al (2011) did not provide
a quality assessment of these studies.
The findings of Bellavite et al (2011) were limited by poor reporting. In many instances it was unclear
whether the positive findings were statistically significant, as p-values were rarely reported. Instead,
general statements were provided, such as “there was a better reduction of symptoms in patients
treated with homeopathy”. The one exception was the reporting of results from the study by Bell et
al (2004) as finding “significantly better outcomes” in the homeopathy patients compared to
placebo, although the exact p-values were still not clear and the specific outcomes that achieved
statistical significance were not identified.
Davidson et al (2011) (AMSTAR score 8/10) examined the evidence for the efficacy of homeopathy
across a variety of chronic conditions, including fibromyalgia. Davidson et al (2011) identified three of
the same Level II studies as the systematic reviews by Perry et al (2010) and Bellavite et al (2011)
(Bell et al, 2004; Fisher 1986; Fisher et al, 1989). Bell et al (2004) was the methodologically strongest
study, scoring well in terms of methodology on the Grading of Recommendations Assessment,
Development and Evaluation (GRADE) and SIGN quality assessment measures. Fisher (1986) and
Fisher et al (1989) were both given low ratings. Bell et al (2004) reported statistically significant
differences favouring homeopathy over placebo on four of the five measures presented in Davidson
et al (2011). One of those measures was the McGill Affective Pain score and was reported as p<0.01;
however this conflicts with reporting of that measure in the systematic review by Perry et al (2010),
which reported a positive but non-significant trend favouring homeopathy and a p-value of p<0.1.
Davidson et al (2011) noted that poor reporting, particularly in Fisher et al (1989) made some results
“impossible to interpret”. Beyond poor reporting, the authors of the systematic review made a
general statement that the current evidence base for homeopathy and fibromyalgia is neither
“sufficiently rigorous nor sufficiently plentiful” to warrant any definite answers. However, Davidson
et al (2011) concluded that the “results do not preclude the possibility of some benefit”.
The remaining four systematic reviews (Baranowsky et al, 2009; de Silva et al, 2010; Holdcraft et al,
2003; Porter et al, 2010), assessed the efficacy of various complementary and alternative medicines
(including homeopathy) in the treatment of fibromyalgia. Due to the broad focus of the reviews, the
information pertaining specifically to the efficacy of homeopathy was limited, and no additional
outcomes or results were provided that have not been discussed above. Two of the reviews had
particularly poor reporting: Baranowsky et al (2009) (AMSTAR score 5/10) did not provide any
p-values to support claims of significance; and Porter et al (2010) (AMSTAR score 6/10) made a broad
statement that a “positive effect” was found for homeopathy, without reporting results according to
separate outcome measures.
Baranowsky et al (2009) only included one of the Level II studies (Bell et al, 2004) that was identified
by the other systematic reviews. Overall, Baranowsky et al (2009) concluded that homeopathy is a
“promising option in the treatment of fibromyalgia” and recommended further studies to confirm
the existing findings.
Porter et al (2010) included two of the Level II studies (Bell et al, 2004; Fisher et al, 1989) that were
identified by the other systematic reviews. Similarly to Baranowsky et al (2009), Porter et al (2010)
concluded that homeopathic treatment was associated with a positive effect on “diagnostic
symptoms” of fibromyalgia. However, Porter et al (2010) noted that the homeopathic treatment
regimens adopted in many of the trials did not reflect the “clinical approach used by most
practitioners” of homeopathy, which involves individually tailored treatments.
Holdcraft et al (2003) (AMSTAR score 5/10) only identified one of the studies (Fisher et al, 1989) for
inclusion in their review and was critical of the cross-over design, particularly the absence of a
wash-out period between the active and placebo interventions. Holdcraft et al (2003) also
questioned the validity of assessing the sleep and pain scores as a combined measure. Overall,
Holdcraft et al (2003) stated that there is “limited evidence” to support the use of homeopathy in
fibromyalgia due to the low quality evidence.
The review by de Silva et al (2010) (AMSTAR score 7/10) identified three of the relevant Level II
studies discussed above (Bell et al, 2004; Fisher et al, 1989; Fisher 1986) and reported that they all
found that homeopathy was associated with an improvement in pain, but were small in size. Similarly
to Holdcraft et al (2003), de Silva et al (2010) questioned the results of Fisher et al (1989), citing an
independent re-analysis that found “no firm support for the efficacy of homeopathic treatment” over
placebo (Colquhoun, 1989). De Silva et al (2010) concluded that independent replication is necessary
due to the fact that each of the three trials used different homeopathic remedies. They also stated
that publication bias is a “major concern” that needs to be considered alongside the positive results.
Reviewer comments
The general consensus across the seven systematic reviews was that Bell et al (2004) was the most
methodologically sound trial of homeopathy and fibromyalgia. The majority of the review authors
highlighted the significant methodological flaws in Fisher et al (1989). In particular, the use of a
cross-over design with no wash-out period between active and placebo treatments was noted as a
major flaw (Holdcraft et al, 2003; Perry et al, 2010). The evidence reviewer concurs that there is a
possibility that carry-over treatment effects may have confounded results in Fisher et al (1989).
In addition, two of the systematic reviews (de Silva et al, 2010; Perry et al, 2010) made reference to
an independent re-analysis of Fisher et al (1989) by Colquhoun (1990) that found “no evidence for the
efficacy of homeopathic treatment when distribution-free randomisation tests were employed”.
Evidence statement
Seven systematic reviews of poor to medium quality identified three randomised controlled trials
(poor to good quality; total of 116 participants, range: 24-62) that compared homeopathy with
placebo for the treatment of people with fibromyalgia.
These studies are of insufficient quality and/or size to warrant further consideration of their findings.
LOC: Low.
Based on the body of evidence evaluated in this review there is no reliable evidence that
homeopathy is more effective than placebo for the treatment of people with fibromyalgia.
Two systematic reviews of poor and medium quality identified one very small randomised controlled
trial (poor quality; 47 participants) that compared homeopathy with other therapies (physiotherapy,
aerobic exercise, anti-inflammatory drugs and anti-depressant medications) for the treatment of
people with fibromyalgia. LOC: Very low.
Based on only one very small study of poor quality there is no reliable evidence on which to draw a
conclusion about the effectiveness of homeopathy compared to the other therapies for the
treatment of people with fibromyalgia.
Table 32 Evidence summary table: the effectiveness of homeopathy for the treatment of fibromyalgia
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Bellavite et al Relton et al (2009) Fibromyalgia Individualised Conventional FIQ Better reduction of symptoms in The review concluded that
(2011) [Level II] patients homeopathic treatment patients treated with homeopathy there was “good positive
[Level I] Quality not prescription compared to control; no adverse evidence” (statistically
AMSTAR: 5/10 specified effects significant evidence of benefit
N=47 from 1-2 properly randomised
SR of trials) for individualised
Bell et al (2004) Fibromyalgia Individualised Placebo Pain, motion Significantly better outcomes of the homeopathy in fibromyalgia.
homeopathy
[Level II] patients homeopathic tenderness, homeopathy group compared to
for multiple
Quality not prescription quality of life placebo Positive evidence was
conditions
specified obtained from Level II studies
N=62 by Fisher et al (1989), Bell et al
(2004), and Relton et al (2009).
Fisher et al (1989) Fibromyalgia Rhus tox Placebo Pain symptoms Slightly positive therapeutic effect in Bellavite et al (2011) also cited
[Level II] patients (individualised) most patients in the homeopathy two reviews: one with
group versus placebo “positive evidence” for
Quality not
individualised homeopathy
specified and fibromyalgia (Baranowsky
d
N=30 et al 2009) and one with
“positive but insufficient
Fisher (1986) Fibromyalgia Arnica, Rhus tox, Placebo Pain symptoms Trend to better improvement in the evidence” (Perry et al 2010).
[Level II] patients Bryonia 6c homeopathic group, not statistically
Quality not significant The review also concluded
specified that there was “negative
N=24 scientific evidence”
(statistically significant
negative evidence (i.e. lack of
evidence of benefit) from 1 or
more Level II studies) for
Arnica, Rhus toxicodendron
and Bryonia 6C for the
treatment of fibromyalgia
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
evidence of an effect
Davidson et al Bell et al (2004) Fibromyalgia Individualised Placebo 25% Statistically significant difference Results do not preclude the
(2011) [Level II] patients homeopathy improvement between groups, favouring possibility of some benefit –
[Level I] SIGN: “good” in tender point homeopathy. Homeopathy group: efficacy was found for the
AMSTAR: 8/10 N=62 pain on 50%; Placebo: 15%; p<0.01 functional somatic syndromes
palpation group (fibromyalgia and
SR of chronic fatigue syndrome).
TPC Significant improvement compared to
homeopathy placebo (p<0.05)
for multiple “Results suggest possible
conditions McGill Significant improvement compared to utility for homeopathy.”
Affective Pain placebo (p<0.01)
score
Fisher et al (1989) Fibromyalgia Rhus Placebo Unclear Positive results for homeopathy,
[Level II] patients toxicodendron 6C especially on tender points
SIGN: “poor”
d
N=30
Fisher (1986) Fibromyalgia Rhus Placebo Pain (VAS) Analysis gave significant differences
[Level II] patients toxicodendron, on pain for indicated remedy
SIGN: “poor” Bryonia alba or
Arnica montana Sleep (VAS) Analysis gave significant differences
N=24 on sleep for indicated remedy
de Silva et al Bell et al (2004) Patients with Individually Placebo Tenderness NR “There was some evidence
(2010) [Level II] fibromyalgia selected from three small studies
f
homeopathic Tender point Significant improvement in favour of regarding three different
[Level I] Jadad score 5
pain homeopathy; p-value NR
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
AMSTAR: 7/10 N=62 remedy Tender point Significant improvement in favour of homeopathic approaches.
count homeopathy; p-value NR Each demonstrated an
SR of CAM for improvement in pain in those
Quality of life Significant improvement in favour of receiving the standardised or
fibromyalgia
homeopathy; p-value NR individualised homeopathic
remedy (compared with
Global health Significant improvement in favour of placebo) and two studies
homeopathy; p-value NR demonstrated improvement
in sleep. While one of these
Depression Significant improvement in favour of trials received the lowest of
homeopathy; p-value NR all Jadad scores (Fisher, 1986),
another received the
Fisher et al (1989) Patients with R. toxicodendron Placebo Tenderness “Homeopathic treatments maximum score (Bell et al,
[Level II] fibromyalgia (6c potency) put significantly improved tenderness as 2004). The third study has
Jadad score 3
f Only patients in up on 125 mg assessed by VAS” (p<0.005) been independently re-
N=30
d whom R. lactose taken 3 analysed and no firm support
toxicodendron times per day. Pain (VAS) “Homeopathic treatments
significantly improved pain as for the efficacy of
was positively This was a cross-
indicated after assessed by VAS” (p<0.005) homeopathic treatment as
over study with found.”
a homeopathic
consultation
treatment Sleep (VAS) “Homeopathic treatments
were included phases of 1 significantly improved sleep
month each in disturbance as assessed by VAS”
random (p<0.005)
sequence
Fisher (1986) Patients with One remedy Placebo Pain Homeopathic treatments significantly
[Level II] fibromyalgia from Arnica improved pain compared with
f montana, placebo as assessed by VAS (p<0.05)
Jadad score 1
N=24 Bryonia alba and
R. toxicodendron Sleep Homeopathic treatments significantly
(all of 6c improved sleep compared with
potency). All the placebo as assessed by VAS (p<0.05)
patients received
the same
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
treatment
throughout a 3
month period
Perry et al Relton et al (2009) Patients with Individually Usual care TPC No significant inter-group differences The effectiveness of
(2010) [Level II] fibromyalgia tailored with one or homeopathy as a
f
homeopathic more of the EuroQol No significant inter-group differences symptomatic treatment for
[Level I] Jadad score 2
AMSTAR: 8/10 N=47 remedies (one 1 following: MYMOPS No significant inter-group differences fibromyalgia remains
hour baseline physiotherapy, unproven (mainly due to the
SR of interview with aerobic HADS No significant inter-group differences limited number of Level II
homeopathy homeopath exercise, anti- studies and the relatively poor
followed by four inflammatory FIQ pain scores No significant inter-group differences scientific quality of the
for
fibromyalgia 30 minute follow drugs, anti- FIQ total score Significantly greater reduction in total existing trials).
up interviews depressants score in the homeopathic group
where remedy compared to the usual care group The authors acknowledged
choice and (p<0.01) that the four included trials
potency can be were all seriously flawed. In
assessed and particular, the re-analysis of
changed Fisher et al (1989) by
Colquhoun suggested there
Bell et al (2004) Patients with 41 remedies Placebo Improvement Significantly greater improvement in
was no evidence for the
[Level II] fibromyalgia used, given as in TPC TPC in intervention group compared
f efficacy of homeopathic
Jadad score 4 LM potencies. to placebo (p<0.05)
treatment when distribution-
N=62 Remedy and
Number of Significantly more patients free randomisation tests were
dosing regimen
patients with experienced a 25% improvement in employed. He criticised Fisher
could be altered
at least a 25% the intervention group (n=13/26) for combining pain and sleep
at any time after
improvement compared to placebo (n=4/27); scores thus invalidating the
consultation with
in TPP on p=0.008 (Fisher’s exact test, two- results. Relton (2004) used a
a homeopath
palpation tailed) design that did not control for
placebo effects and was also
Fibromyalgia Significantly greater improvement in insufficiently powered due to
scores homeopathy compared to placebo a high drop-out rate in the
group (p<0.05)
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Global health Significantly greater improvement in usual care group.
rating homeopathy compared to placebo
(adjusted for group (p<0.05). At 6 months, those
anger and who stayed in the experimental group
depression) had a greater gain in global health
than the placebo-switch group
Fisher et al (1989) Patients with Rhus Placebo – two Number of Significantly more patients improved
[Level II] fibromyalgia toxicodendron tablets three patients with in the intervention group (n=53)
f 6c, two tablets times daily improved pain compared to placebo (n=27);
Jadad score 4
N=30
d three times daily and sleep (pain p=0.0052
and sleep VAS
– combined
measure)
Fisher (1986) Patients with One of three Placebo – Pain No significant difference between
[Level II] fibromyalgia homeopathic twice a day intervention groups and placebo
f remedies (Rhus (p=0.19)
Jadad score 3
N=24 toxicodendron,
Arnica Montana, Pain – Significant difference between
or Bryonia) in 6c subgroup intervention and placebo groups at 2
potency twice a analysis and 3 months when those with
day “poorly indicated” homeopathic
remedies were removed, leaving only
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
those with “optimal fit” (p<0.05)
Porter et al Bell et al (2004) Patients with Homeopathy – Placebo Physical and Positive effect reported for Both fibromyalgia studies
(2010) [Level II] fibromyalgia details not psychological homeopathy – outcomes not reported reported that homeopathic
f
[Level I] Jadad score 5 specified outcomes separately treatment had a positive
AMSTAR: 6/10 N=62 effect on diagnostic
symptoms of fibromyalgia.
Fisher et al (1989) Patients with Rhus Placebo Physical Positive effect reported for
SR of CAM for
[Level II] fibromyalgia toxicodendron outcomes, QoL homeopathy – outcomes not reported However, the treatments
multiple f
Jadad score 3 separately used in the review do to
conditions d
N=30 necessarily reflect the “clinical
approach used by most
practitioners to treat these
illnesses, which include a mix
of natural and
unconventionally used
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
medications and natural
hormones tailored to each
individual case”.
Baranowsky et Bell et al (2004) Patients with Individually Placebo (oral TPC Significant improvement in active Significant improvement in
al (2009) [Level II] fibromyalgia prescribed daily liquid) group compared to placebo; p-value active group in TPC and TP
[Level I] Quality score homeopathic NR pain on palpation, appraisal of
AMSTAR: 5/10 according to 16 remedies of daily fibromyalgia scores, global
oral liquid, TPP on Significant improvement in active health ratings and helpfulness
formal criteria:
flexibly dosed LM palpation group compared to placebo; p-value of treatment as compared to
SR of CAM for 57.5/100
potencies NR placebo group.
fibromyalgia N=62
McGill Pain NR
Questionnaire Homeopathy is a promising
option in the treatment of
Fibromyalgia Significant improvement in active fibromyalgia, although further
quality of life group compared to placebo; p-value studies are needed to confirm
scores NR the findings.
POMS NR
Holdcraft et al Fisher et al (1989) Patients with Rhus Placebo TPC Mean number of tender points was There is limited evidence to
(2003) [Level II] fibromyalgia toxicodendron reduced by 25% in active group. support the use of
[Level I] CONSORT score: (poison ivy) Significant improvement compared to homeopathy for fibromyalgia
AMSTAR: 5/10 10 placebo (p<0.05) due to the low quality of the
d Level II study.
N=30
Number of Significant improvement in active
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
SR of CAM for patients with compared to placebo group (p<0.05)
fibromyalgia improved pain Results limited by the fact
and sleep (pain that sleep and pain scores
and sleep VAS were not reported separately
– combined and also by the fact that there
measure) was no wash-out period
between the active and
placebo interventions.
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; CAM, complementary and alternative medicines; CONSORT, Consolidated Standards of Reporting Trials; FIQ,
Fibromyalgia Impact Questionnaire; MSP, McGill Sensory Pain; NR, not reported; POMS, Profile of Mood States scale; SIGN, Scottish Intercollegiate Guidelines Network quality analysis; SR,
systematic review; TP, tender point; TPC, tender point count; TPP, tender point pain; VAS, visual analogue scale.
a
Level of evidence as assessed by the evidence reviewer
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit
c
Study quality as reported in the systematic review
d
Refers to the number of participants that completed the cross-over periods
e
A later re-analysis of the data (Colquhoun 1991) found that no significant treatment effects occurred after the first treatment period
f
The Jadad scale assesses the quality of published clinical trials based methods relevant to random assignment, double blinding and the flow of patients. The range of possible scores is zero
(bad quality) to 5 (good quality).
Evidence statement
One systematic review of good quality identified one small randomised controlled trial (quality not
reported; 80 participants) that compared homeopathy (Traumeel R) with placebo for the treatment
of people with knee joint haematoma. LOC: Very low.
Based on only one small study of unknown quality there is no reliable evidence on which to draw a
conclusion about the effectiveness of homeopathy compared to placebo for the treatment of people
with knee joint haematoma.
Table 33 Evidence summary table: the effectiveness of homeopathy for the treatment of knee joint haematoma
Study ID Included study Patient Intervention Comparator Outcome Results as Systematic review interpretation
a
Level of Level of evidence population reported in the
a c
evidence Quality systematic
b review
Quality Sample size
Cucherat et al Thiel (1991) Patients with Intraarticular Intraarticular Joint Significant “It is clear that the strength of available
(2000) [Level II] knee joint Traumeel R injections of sodium mobility difference in evidence is insufficient to conclude that
[Level I] Quality not specified haematoma chloride favour of homeopathy is clinically effective.”
d homeopathy
AMSTAR: 10/11 N=80
(p=0.026) (Note: this conclusion refers to all clinical
SR of conditions and is not specific to knee joint
homeopathy for haematoma)
multiple
conditions
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; SR, systematic review.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
d
73 patients were evaluated.
4.9.6 Osteoarthritis
The effectiveness of homeopathy in osteoarthritis was assessed in three systematic reviews as
summarised in Table 34 and Table 35. Overall, the systematic reviews included four Level II studies
(Nahler et al, 1998; Shealy et al, 1998; Shipley et al, 1983; van Haselen and Fisher, 2000) and one
Level III-2 study (Birnesser et al, 2003) (Table 34). The AMSTAR quality ratings of the five systematic
reviews ranged from 5/10 (Bellavite et al, 2011) to 6/10 (De Silva et al, 2011; Long and Ernst, 2001).
Table 34 Matrix indicating the studies that were included in the systematic reviews of osteoarthritis
Study ID
Van Haselen Nahler et al Shealy et al Shipley et al Birnesser et
and Fisher (1998) (1998) (1983) al (2003)
(2000) [Level II] [Level II] [Level II] [Level III-2]
[Level II]
De Silva et al (2011)
Systematic review
[Level I]
Long and Ernst
(2001)
[Level I]
Bellavite et al (2011)
[Level I/III]
De Silva et al (2011) (AMSTAR score 6/10) provided a broad review of the efficacy of a range of
complementary and alternative medicines in the management of osteoarthritis. Three Level II studies
were identified that were specific to homeopathy and osteoarthritis (Shealy et al, 1998; Shipley et al,
1983; van Haselen and Fisher, 2000; median Jadad score of 3). One Level II study with three parallel
treatment arms reported that homeopathy and placebo were both less effective than fenoprofen in
terms of pain on movement and pain at rest in hip or knee osteoarthritis (Shipley et al, 1983). It is
assumed that the results were statistically significant; however, no numerical evidence was provided
in order to confirm that assumption. The authors concluded that the evidence base was
“insufficiently large” to provide conclusive evidence for or against homeopathy in osteoarthritis.
Long and Ernst (2001) (AMSTAR score 6/10) identified four Level II studies for inclusion in their
systematic review of homeopathy for the treatment of osteoarthritis (Nahler et al, 1998; Shealy et al,
1998; Shipley et al, 1983; van Haselen and Fisher, 2000). The Level II studies were of reasonable to
good quality with three scoring a Jadad score of 3 and one scoring 4. Long and Ernst (2001)
confirmed the assumption made above, that fenoprofen produced “highly statistically significant”
pain relief compared to homeopathy and placebo in Shipley et al (1983). In contrast, homeopathy
was found to be “at least as effective” as a conventional NSAID gel in van Haselen and Fisher (2000),
according to Long and Ernst (2001), and not significantly different to conventional medications
(hyaluronic acid and paracetamol) in the remaining two Level II studies (Nahler et al, 1998; Shealy et
al, 1998).
Long and Ernst (2001) reported that homeopathy was inferior to conventional medication in one trial
and not significantly different in three others. As such, they concluded that there is a “positive trend
towards the effectiveness of combination homeopathic preparations”. However, they acknowledge
that the limited evidence base precludes them from drawing “firm conclusions as to the
effectiveness of combination homeopathic remedies” for osteoarthritis.
Bellavite et al (2011) (AMSTAR score 5/10) conducted a systematic review of homeopathy and
immunology in three broad clinical areas, one of which was “Arthrorheumatic diseases and
osteoarthritis”. The Level II and Level III-2 osteoarthritis studies included in this systematic review
included four previously discussed Level II studies (Nahler et al, 1998; Shealy et al, 1998; Shipley et al,
1983; van Haselen and Fisher, 2000) and one large (N=592) Level III-2 study (Birnesser et al, 2003) of
patients with knee osteoarthritis. In addition to the findings discussed above, Bellavite et al (2011)
reported that the complex homeopathic formulation used in Shealy et al (1999) was associated with
better pain relief than acetaminophen, but not to a statistically significant extent. The Level III-2
study by Birnesser et al (2003) compared symptom scores between patients who received a
homeopathic treatment (Zeel compositum-N) and those who received COX-2 inhibitors, and reported
that the homeopathic regimen was equivalent to the COX-2 inhibitors.
Overall, Bellavite et al (2011) concluded that there is “good positive evidence” for Zeel compositum-N
in the treatment of osteoarthritis based on the findings of Nahler et al (1998) and Birnesser et al
(2003); and “negative scientific evidence” (i.e. lack of evidence of benefit) for Rhus toxicodendron 6X
in the treatment of osteoarthritis based on the findings of Shipley et al (1983). The authors of the
systematic review suggest that the negative result of the trial by Shipley et al (1983) could be a result
of the non-individualised homeopathic remedy used in that trial. They state that it appears that “the
tested remedy cannot be effective if prescribed based only upon a diagnosis of disease, but without
individualisation of the therapy”.
Furthermore, Bellavite et al (2011) suggest that the reported finding of equivalence between a
homeopathic gel and piroxicam gel found in van Haselen and Fisher (2000) is important due to the
fact that the benefit of piroxicam gel over placebo has been previously established in several
double-blind Level II studies (including Norris and Guttadauria, 1987). The authors therefore suggest
that there is “indirect proof of the effectiveness of the tested homeopathic remedy” compared to
placebo.
Reviewer comments
Several of the systematic reviews reported that the homeopathic interventions were not significantly
different to conventional medications, including piroxicam gel, hyaluronic acid, paracetamol and
COX-2 inhibitors (based on Level II and III-2 evidence). However, the Level II study by Shipley et al
(1983) (identified by all four systematic reviews) reported that homeopathy was significantly inferior
to fenoprofen for the treatment of osteoarthritic pain.
The authors of the systematic reviews acknowledged that there were some serious methodological
flaws in the included studies. Importantly, the cross-over Level II study by Shipley et al (1983) had no
wash-out period between treatments. The relatively short duration of the trials (4 to 6 weeks) was
also noted as a potential limitation.
The evidence reviewer notes that Bellavite et al (2011) may have over-interpreted their results by
claiming that the “equivalence” of a homeopathic gel and piroxicam gel provides “indirect proof” of
the effectiveness of homeopathy over placebo. In addition, the same review suggested that the
negative outcome of Rhus toxicodendon 6X compared to fenoprofen was possibly due to the fact that
an individualised homeopathic regimen was not used, without any scientific evidence to support the
claim.
A major limitation across all of the systematic reviews was a lack of information regarding patient
characteristics (age, gender, duration of osteoarthritis), and reporting of primary outcomes and
results that were often difficult to interpret. It was unclear whether the gaps in reporting were due to
poor-quality reporting in the included trials or the systematic reviews themselves.
Evidence statement
Three systematic reviews of poor to medium quality identified one very small randomised controlled
trial (medium quality; 36 participants) that compared homeopathy (Rhus toxicodendron) with
placebo for the treatment of people with osteoarthritis. LOC: Very low.
Based on only one very small study there is no reliable evidence on which to draw a conclusion about
the effectiveness of homeopathy compared to placebo for the treatment of people with
osteoarthritis.
Three systematic reviews of poor to medium quality identified four randomised controlled trials
(medium quality; total of 406 participants, range: 36 to 184) and one large prospectively designed,
non-randomised controlled study (quality not reported; 592 participants) that compared
homeopathy with other therapies (fenoprofen, piroxicam gel, hyaluronic acid, paracetamol and COX-
2 inhibitors) for the treatment of people with osteoarthritis.
These studies are of insufficient quality and/or size to warrant further consideration of their findings.
LOC: Low.
Based on the body of evidence evaluated in this review there is no reliable evidence that
homeopathy is as effective as the other therapies for the treatment of people with osteoarthritis.
Table 35 Evidence summary table: the effectiveness of homeopathy for the treatment of osteoarthritis
Study ID Included study Patient Intervention Comparator Outcome Results as reported in Systematic review
Level of Level of population the systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
De Silva et al van Haselen and Patients with Local application of 1g piroxicam gel Mean pain No difference between the “Although there was some
(2011) Fisher (2000) osteoarthritis 1g Spiroflor gel (0.5%) applied reduction (VAS) two treatment groups promising evidence, the
[Level I] [Level II] three times daily three times evidence base was either
AMSTAR: 6/10 Quality not for 4 weeks daily for 4 insufficiently large or the
d weeks evidence base was
specified
SR of CAM for N=184 inconsistent”, limiting the
osteoarthritis ability to draw any conclusions
Shealy et al (1998) Patients with A homeopathic Paracetamol Reduction in knee No difference between about the efficacy of
[Level II] knee preparation 2.6g/day pain homeopathic preparation homeopathy in osteoarthritis.
Quality not osteoarthritis including Rhus and paracetamol
d
specified toxicodendron 12x,
N=65 Causticum 12x and
Lac Vaccinum 12x)
Shipley et al (1983) Patients with Rhus Placebo or Pain on movement Homeopathy less effective
[Level II] hip or knee toxicodendron 6x fenoprofen (measured by both than fenoprofen; no
Quality not osteoarthritis 600mg three 10cm VAS and four difference compared to
d times daily point pain scores) placebo
specified
N=36 Pain at rest Homeopathy less effective
(measured by both than fenoprofen; no
10cm VAS and four difference compared to
point pain scores) placebo
Long and Ernst van Haselen and Patients with Topical application Topical Mean pain 16.5mm (SD 24.6) VAS in Two of the four included trials
(2001) Fisher (2000) knee of 1g SRL® gel to application of reduction (VAS) the intervention group present “positive evidence for
[Level I] [Level II] osteoarthritis the knee three 1g 0.05% (n=86); 8.1mm (SD 25.7) in the effectiveness of
e times daily piroxicam gel to the comparator group. combination homeopathic
AMSTAR: 6/10 Jadad score 3
N=184 the knee three Difference between preparations in comparison to
SR of times daily treatment groups was conventional medications”.
homeopathy 8.4mm (95% CI 0.8, 15.9),
for adjusted for pain at A third concluded that “Rhus
baseline was 6.8mm (95%
Study ID Included study Patient Intervention Comparator Outcome Results as reported in Systematic review
Level of Level of population the systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
osteoarthritis CI -0.3, -13.8) toxicodendron was significantly
inferior to conventional
Joint tenderness No significant difference medication”, while the fourth
(measured by the between treatment groups reported that homeopathic gel
single-joint Ritchie (p=0.78) was “at least as effective as a
index) conventional NSAID gel”.
Nahler et al (1998) Patients with Two 2mL intra- One 2mL intra- Pain during the No significant difference
[Level II] knee articular Zeel® articular night between treatment groups Overall, there appears to be a
Jadad score 3
e osteoarthritis injections per week Hyalart® (p=0.3077) positive trend towards the
N=121 (hyaluronic acid) effectiveness of combination
injection per Duration of No significant difference homeopathic preparations;
week morning stiffness between treatment groups however, the authors
(p=0.9211) acknowledged the small
number of Level II studies from
Final assessment by No significant difference
which their conclusions are
physician and between treatment groups
drawn.
patient (p-value NR)
Study ID Included study Patient Intervention Comparator Outcome Results as reported in Systematic review
Level of Level of population the systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Shealy et al (1998) Patients with Oral administration Paracetamol Percentage of Non-significant difference
[Level II] knee of 10 drops of a capsules four patients achieving between treatment groups
e osteoarthritis homeopathic times daily clinically useful pain (55% of patients receiving
Jadad score 3
N=65 preparation (Rhus (daily dose of reduction (40% or homeopathy and 38% of
toxicodendron, 2600mg) and greater), measured those receiving
Causticum and Lac liquid placebo daily by VAS paracetamol)
Vaccinum) and
placebo capsules
four times daily
Shipley et al (1983) Patients with Five drops of Rhus Oral Pain at rest No significant difference
[Level II] hip or knee toxicodendron administration (measured by both between homeopathy and
e osteoarthritis (6x:1/1000000 of two 10cm VAS and four placebo; fenoprofen
Jadad score 4
N=36 dilution) three fenoprofen point pain scores) produced highly significant
times daily and capsules (each pain relief compared with
placebo capsules 300mg) three homeopathy and placebo
times daily and
placebo drops; Pain on movement No significant difference
or placebo (measured by both between homeopathy and
drops and 10cm VAS and four placebo; fenoprofen
placebo point pain scores) produced highly significant
capsules pain relief compared with
homeopathy and placebo
Bellavite et al van Haselen and Patients with Local application of Piroxicam gel Mean pain No significant inter-group There is “good positive
(2011) Fisher (2000) knee a homeopathic gel reduction (VAS) differences. Homeopathy evidence” for Zeel
Study ID Included study Patient Intervention Comparator Outcome Results as reported in Systematic review
Level of Level of population the systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
[Level I/III] [Level II] osteoarthritis group: 16.5mm; Control compositum-N in the
AMSTAR: 5/10 Quality not group: 8.1mm treatment of osteoarthritis
reported (Nahler et al 1998; Birnesser et
SR of N=172 al 2003).
homeopathy
Nahler et al (1998) Patients with Zeel compositum-N Hyaluronic acid, Pain during motion Equivalence of the There is “negative scientific
for multiple
[Level II] knee intrarticular (subjective scores), homeopathic complex and evidence” (i.e. lack of evidence
conditions
Quality not osteoarthritis injection tolerability hyaluronic acid of benefit) for Rhus
specified toxicodendron 6X in the
N=114 treatment of osteoarthritis.
The negative result of the trial
Shealy et al (1998) Patients with Complex Acetaminophen Motion tenderness Equivalence of
by Shipley et al (1983) suggests
[Level II] knee homeopathic (VAS) homeopathic formulation
that “the tested remedy
Quality not osteoarthritis formulation – Rhus and acetaminophen
cannot be effective if
specified toxicodendron,
Pain relief Better pain relief in the prescribed based only upon a
N=65 Causticum, and Lac
homeopathy group (55% diagnosis of disease, but
vaccinum
compared to 38% with without individualisation of
acetaminophen), but not the therapy”.
statistically significant
With regards to the findings of
Shipley et al (1983) Patients with Rhus Placebo or Symptoms No effect of homeopathy van Haselen and Fisher (2000)
[Level II] hip and knee toxicodendron 6x fenoprofen versus placebo; fenoprofen the authors of the systematic
Quality not osteoarthritis better than homeopathy review state that “since
specified and placebo double-blind clinical trials
N=36 involving patients with
osteoarthritis of the knee
Birnesser et al Patients with Zeel compositum-N COX-2 inhibitors Symptoms scores Equivalence of
showed the piroxicam topical
(2003) knee homeopathic complex and
gel to the significantly more
[Level III-2] osteoarthritis COX-2 inhibitors
effective than placebo (Norris
Quality not and Guttadauria, 1987), this
specified equivalence may be
N=592 considered as indirect proof of
the effectiveness of the tested
Study ID Included study Patient Intervention Comparator Outcome Results as reported in Systematic review
Level of Level of population the systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
homeopathy remedy”.
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; CAM, complementary and alternative medicines; SD, standard deviation; SR, systematic review.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
d
The systematic review reported that the median Jadad score was 3.
e
The Jadad scale assesses the quality of published clinical trials based methods relevant to random assignment, double blinding and the flow of patients. The range of possible scores is zero
(bad quality) to 5 (good quality).
Table 36 Matrix indicating the studies that were included in the systematic reviews of rheumatoid arthritis
Study ID
Fisher (2001) Gaus (1993) Andrade (1991) Gibson (1980) Gibson (1978)
[Level II] [Level II] [Level II] [Level II] [Level III-2]
Macfarlane
et al (2011)
Systematic review
[Level I]
Cucherat et
al (2000)
[Level I]
Bellavite et
al (2011)
[Level I/III]
The systematic review by Macfarlane et al (2011) (AMSTAR score of 8/10) aimed to critically evaluate
the evidence regarding complementary and alternative medicine taken orally or applied topically
(excluding fish oil) in the treatment of rheumatoid arthritis. For the homeopathy intervention, two
Level II studies were identified that both received a Jadad score of 3 (Fisher, 2001; Andrade, 1991).
Both Level II studies assessed the effect of homeopathy in patients with rheumatoid arthritis
compared with placebo. Neither study reported a significant difference between homeopathy and
placebo for any of the primary outcomes. The only exception was in Fisher (2001), where significantly
lower pain scores were detected after placebo therapy. Macfarlane et al (2011) thus concluded that
“the available evidence does not currently support the use of homeopathy in the management of
rheumatoid arthritis”.
Cucherat et al (2000) (AMSTAR score 10/11) aimed to answer the question of “whether there is any
evidence from randomised controlled trials that homeopathy is efficacious for the treatment of
disease in humans”. The systematic review included one Level II study (Gaus, 1993) that investigated
the effect of homeopathic Rheumaselect in patients with rheumatoid arthritis. Cucherat et al (2000)
reported a significant difference (p=0.018) in favour of homeopathy, based on a composite criteria of
treatment success in this Level II study. The quality of Gaus (1993) was not formally assessed by
Cucherat et al (2000); however, a general comment was made about all of the included studies that
“the strength of this evidence is low because of the low methodological quality of the trials”. Overall,
the authors concluded that “it is clear that the strength of available evidence is insufficient to
conclude that homeopathy is clinically effective”.
Bellavite et al (2011) (AMSTAR score 5/10) conducted a systematic review of homeopathy and
immunology in three broad clinical areas, one of which was “Arthrorheumatic diseases and
osteoarthritis”. Three Level II studies and one Level III-2 study were identified for the rheumatoid
arthritis indication. The Level II studies included Fisher (2001), which was also included in the
systematic review by Macfarlane et al (2011). A different interpretation of the results was given,
however, in that Bellavite et al (2011) reported that there was no effect of homeopathy over placebo
in the pain and articular index outcome. Similar to the other systematic reviews, Bellavite et al (2011)
concurred that there were “slight but not significant” differences in the homeopathy group over
placebo in the Level II study by Andrade (1991).
Gibson (1980) was a Level II study that assessed the effect of individualised homeopathy in patients
with rheumatoid arthritis. The study found an improvement in symptoms in 83% of patients in the
homeopathy group and 22% of patients in the placebo group. The significance of the results,
however, was not reported. Finally, Gibson (1978) was a Level III-2 study of individualised
homeopathy in comparison to salicylate or placebo. The study reported better relief in the
homeopathic group compared to salicylate or placebo, although the significance of the results was
not reported. Bellavite et al (2011) noted that the trial was neither randomised nor double-blind so it
was not possible to distinguish between those effects due to the treatment and those due to the
difference in practitioner. Overall, Bellavite et al (2011) found that the evidence on rheumatoid
arthritis was “unclear or conflicting”. It noted “positive evidence from one RCT and one non-
randomised controlled trial. No evidence from two RCTs”.
Evidence statement
Three systematic reviews of poor to good quality identified four randomised controlled trials
(unreported or medium quality; total of 378 participants, range: 44-176) and one medium-sized
prospectively designed, non-randomised controlled study (quality not reported; 195 participants)
that compared homeopathy with placebo for the treatment of people with rheumatoid arthritis.
These studies are of insufficient quality and/or size to warrant further consideration of their findings.
LOC: Low.
Based on the body of evidence evaluated in this review there is no reliable evidence that
homeopathy is more effective than placebo for the treatment of people with rheumatoid arthritis.
One systematic review of poor quality identified one medium-sized prospectively designed, non-
randomised controlled study (quality not reported; 195 participants) that compared homeopathy
with salicylate for the treatment of people with rheumatoid arthritis. LOC: Low.
Based on only one study of unknown quality there is no reliable evidence on which to draw a
conclusion about the effectiveness of homeopathy compared to salicylate for the treatment of
people with rheumatoid arthritis.
Table 37 Evidence summary table: the effectiveness of homeopathy for the treatment of rheumatoid arthritis
Study ID Included Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of study population systematic review interpretation
a
evidence Level of
b a
Quality evidence
c
Quality
Sample size
Macfarlane et Fisher (2001) Seropositive Homeopathic Placebo Pain Significantly lower pain scores “The available evidence
al (2011) [Level II] rheumatoid medicines in 6cH after placebo therapy does not currently support
d
[Level I] Jadad score 3 arthritis patients or 30cH. The most the use of homeopathy in
on stable commonly used Articular index No difference between the management of RA.”
AMSTAR: 8/10 N=112
treatment were Rhus treatment groups
Andrade (1991) Patients with Individualised Placebo Morning stiffness No difference between
[Level II] rheumatoid homeopathy treatment groups
d arthritis according
Jadad score 3
to ARA criteria 15-m walking time No difference between
N=44 treatment groups
Study ID Included Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of study population systematic review interpretation
a
evidence Level of
b a
Quality evidence
c
Quality
Sample size
treatment groups
Cucherat et al Gaus (1993) Patients with Rheumaselect Placebo Composite criteria of Significant difference in favour “It is clear that the
(2000) [Level II] rheumatoid treatment success of homeopathy strength of available
[Level I] Quality not arthritis (p=0.018) evidence is insufficient to
AMSTAR: 10/11 specified conclude that homeopathy
N=176 is clinically effective.”
SR of
homeopathy (Note: this conclusion
for multiple refers to all clinical
conditions conditions and is not
specific to rheumatoid
arthritis)
Bellavite et al Fisher (2001) Patients with NSAIDS + NSAIDS + Pain and articular No effect of homeopathy over Unclear of conflicting
(2011) [Level II] rheumatoid individualised placebo index the placebo evidence – positive
[Level I/III] Quality not arthritis homeopathic evidence from one Level II
AMSTAR: 5/10 specified prescription and one Level III-2 study.
N=112 No evidence from two
SR of Level II studies.
Andrade (1991) Patients with Individualised Placebo Overall improvement Slight but not significant
homeopathy
[Level II] rheumatoid homeopathic (physician assesses) differences in the homeopathy
for multiple
Quality not arthritis prescription group over the placebo
conditions
specified Homeopathy group: 59%
N=44 Placebo group: 44%
Gibson (1980) Patients with Individualised Placebo Improvement in Significance of results not
[Level II] rheumatoid homeopathic symptoms reported
Quality not arthritis prescription (spontaneous pain, Homeopathy group: 83%
specified stiffness in the joint, Placebo group: 22%
Study ID Included Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of study population systematic review interpretation
a
evidence Level of
b a
Quality evidence
c
Quality
Sample size
N=46 prensile strength)
Gibson (1978) Patients with Individualised Salicylate or Medical assessment Better relief in the
[Level III-2] rheumatoid homeopathic placebo homeopathic group compared
Quality not arthritis prescription to salicylate or placebo (p=NR)
specified
N=195
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; ARA, American Rheumatism Association; CAM, complementary and alternative medicines; cH, Hahnemannian
centesimal scale; ESR, erythrocyte sedimentation rate; NR, not reported; NSAIDS, non-steroidal anti-inflammatory drugs; SR, systematic review.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
d
The Jadad scale assesses the quality of published clinical trials based methods relevant to random assignment, double blinding and the flow of patients. The range of possible scores is zero
(bad quality) to 5 (good quality).
4.10 Neurological
4.10.1 Broca’s aphasia in people who have had a stroke
The effectiveness of homeopathy for the treatment of Broca’s aphasia in people who have had a
stroke was assessed in one Level I/III systematic review (Linde and Melchart, 1998; AMSTAR score
8/11) as summarised in Table 38. The authors conducted a broad review of the efficacy of
individualised homeopathy across a range of clinical areas. One study was identified that assessed
the efficacy of individual homeopathic simillimum compared to placebo for the treatment of Broca’s
aphasia (Master, 1987). The study was either a Level II or Level III-1 study; however, the method of
allocation was not described and it is therefore not clear whether the study was randomised or
pseudo-randomised. In the homeopathy group, 92% of patients were assessed as globally improved
(physician-rated) compared to 25% in the placebo group. Linde and Melchart (1998) calculated a rate
ratio of 3.67 (95% CI 1.37, 9.84), indicating significant inter-group differences. However the authors
of the systematic review also stated that the study by Master (1987) was “completely inassessible”
due to “totally insufficient reporting” and questioned the reliability of the extremely positive results.
Overall, Linde and Melchart (1998) gave the study a Jadad score of 1 and an internal validity rating of
1, suggesting that the trial was of very poor quality.
Evidence statement
One systematic review of medium quality identified one very small prospectively designed and
controlled study (poor quality; 36 participants) that compared homeopathy (Simillimum) with
placebo for the treatment of Broca’s aphasia in people who have had a stroke. LOC: Very low.
Based on only one very small poor quality study there is no reliable evidence on which to draw a
conclusion about the effectiveness of homeopathy compared to placebo for the treatment of Broca’s
aphasia in people who have had a stroke.
Table 38 Evidence summary table: the effectiveness of homeopathy for the treatment of Broca’s aphasia in people who have had a stroke
Study ID Included study Patient Intervention Comparator Outcome Results as reported in Systematic review
Level of Level of population the systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Linde and Master (1987) Stroke patients Individualised Placebo Number of patients Significantly favours “Totally insufficient report –
d
Melchart [Level II or III-1] with Broca’s simillimum assessed globally as homeopathy. completely inassessible;
(1998) d aphasia improved (physician- extremely positive results.”
Quality: 1,1 Intervention group: 22/24
[Level I/III] N=36 rated) (92%); Control group:
AMSTAR: 8/11 3/12 (25%)
4.10.2 Stroke
The effectiveness of homeopathy for the treatment of stroke was assessed in one systematic review
as summarised in Table 39 (Ernst and Pittler, 1998; AMSTAR score 6/10). The systematic review
performed by Ernst and Pittler (1998) assessed the efficacy of homeopathic Arnica for the treatment
of various clinical conditions. The systematic review included one Level II study (Livingstone, 1991)
that was assessed by the authors of the systematic review to be of reasonable quality (Jadad score of
3). The Level II study recruited patients admitted to hospital within seven days of suffering from a
stroke and treated them with homeopathic Arnica (in M potency) or placebo. Mortality rates at 3
months were compared between the two groups and no statistically significant difference was found
between the intervention and control arms. Ernst and Pittler (1998) did not provide a conclusion that
was specific to the effectiveness of homeopathic Arnica for the treatment of stroke; however, they
concluded that in general the assertion that “homeopathic Arnica is clinically effective beyond a
placebo effect is not based on methodologically sound placebo-controlled trials”.
Evidence statement
One systematic review of medium quality identified one very small randomised controlled trial
(medium quality; 40 participants) that compared homeopathy (Arnica) with placebo for reducing
mortality in people who have had a stroke. LOC: Very low.
Based on only one very small study there is no reliable evidence on which to draw a conclusion about
the effectiveness of homeopathy compared to placebo for the treatment of people who have had a
stroke.
Table 39 Evidence summary table: the effectiveness of homeopathy for the treatment of stroke
Study ID Included study Patient Intervention Comparator Outcome Results as reported in Systematic review
Level of Level of population the systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Ernst and Pittler Livingston (1991) Patients admitted Arnica (M Placebo 3 month mortality No significant difference “The hypothesis claiming
(1998) [Level II] to hospital up to 7 potency) that homeopathic Arnica is
d
[Level I] Jadad score 3 days after acute clinically effective beyond a
AMSTAR: 6/10 N=40 event for the placebo effect is not based
treatment of stroke on methodologically sound
SR of placebo-controlled trials.”
homeopathy for
multiple (Note: this conclusion refers
conditions to all clinical conditions and
is not specific to stroke)
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; SR, systematic review.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
d
The Jadad scale assesses the quality of published clinical trials based methods relevant to random assignment, double blinding and the flow of patients. The range of possible scores is zero
(bad quality) to 5 (good quality).
Table 40 Matrix indicating the studies that were included in the systematic reviews of migraine and headache
Study ID
Straumsheim et Walach et al Whitmarsh et Brigo and
a
al (1997) (1997) al (1993/1997) Serpelloni
[Level II] [Level II] [Level II] (1991)
[Level II]
Owen and Green (2004)
[Level I]
Systematic review
Cucherat et al (2000)
[Level I]
Vernon et al (1999)
[Level I]
Linde and Melchart (1998)
[Level I]
a
Whitmarsh et al (1993) and Whitmarsh et al (1997) were the same study. The study was referred to as Whitmarsh et al
(1993) in Cucherat et al (2000) and Whitmarsh et al (1997) in Owen and Green (2004) and Linde and Melchart (1998).
The quality of the systematic reviews (as assessed by the AMSTAR tool) varied greatly; from 5/10
(Vernon et al, 1999) to 10/11 (Cucherat et al, 2000). Neither of the two systematic reviews that
focused specifically on migraine and chronic headache (Owen and Green, 2004; Vernon et al, 1999)
conducted a meta-analysis. The remaining two reviews presented pooled efficacy results across all
conditions (including migraine/headache).
The systematic review by Owen and Green (2004) (AMSTAR score 6/10) assessed the efficacy of
homeopathy in the treatment of migraine and chronic headache based on all four of the Level II
studies identified by the reviews: two low quality Level II studies (Brigo and Serpelloni, 1991;
Whitmarsh et al, 1993/1997) and two Level II studies of reasonable quality (Straumsheim et al, 1997;
Walach et al, 1997). All four Level II studies reported the frequency, intensity and severity of attacks
as well as the level of medication used in the treatment group, compared to the placebo group. In
Brigo and Serpelloni (1991), the authors reported that homeopathy was superior to placebo across
all four outcomes, although no p-values were provided in the systematic review. The other three
Level II studies reported no differences between the homeopathy and placebo groups.
Owen and Green (2004) concluded that there is “insufficient evidence to support or refute the use of
homeopathy for tension type, cervicogenic and migraine headache”. The lack of conclusive evidence
was partly attributed to the limited number of studies and also to design flaws in the included
studies. Importantly, Owen and Green (2004) raised concerns about the short duration of the trials
(3-4 months), stating that homeopathy is considered a “gentle” or “soft” therapeutic intervention in
which the treatment effects may be small and may not be clinically observable during short periods
of treatment. This was said to be particularly pertinent to patients with chronic illnesses, where
therapeutic benefits may not be immediately detectable.
Cucherat et al (2000) (AMSTAR score 10/11) aimed to answer the question of “whether there is any
evidence from randomised controlled trials that homeopathy is efficacious for the treatment of
disease in humans”. Cucherat et al (2000) included the same Level II study by Whitmarsh et al,
1993/1997 that was included in the review by Owen and Green (2004). Whitmarsh et al (1993/1997)
recruited patients that suffer from headaches and compared the efficacy of individualised
homeopathy and placebo in terms of mean attack frequency over the course of the trial. No details
were provided about the duration of the study. No statistically significant difference was found
between the homeopathy and placebo groups in terms of mean attack frequency (p=0.83). The
quality of Whitmarsh et al (1993/1997) was not formally assessed by Cucherat et al (2000); however,
a general comment was made about all of the included studies that “the strength of this evidence is
low because of the low methodological quality of the trials”. In addition, Cucherat et al (2000) also
noted that the studies of high methodological quality were more likely to provide negative results for
homeopathy compared to the lower quality studies. Overall, the authors concluded that “it is clear
that the strength of available evidence is insufficient to conclude that homeopathy is clinically
effective”.
Vernon et al (1999) (AMSTAR score 5/10) conducted a systematic review that assessed a broad range
of complementary and alternative medicines in the treatment of tension-type and cervicogenic
headache. Vernon et al (1999) included only one of the Level II studies (Walach et al, 1997), which
specifically related to homeopathy and headache. Walach et al (1997) reported no significant
difference between the placebo and individualised homeopathy groups on “any important clinical
variables” over the 12-week study period. The Level II study was assessed by the authors of the
systematic review to be of high quality (86% using a quality review protocol modified from van
Tulder et al, 1997) and they concluded that the results “might recommend against the use of
homeopathy for the treatment of tension-type headache”.
Linde and Melchart (1998) (AMSTAR score 8/11) identified all four of the Level II studies identified by
the reviews for inclusion in their systematic review of individualised homeopathy in treating a range
of clinical conditions. Linde and Melchart (1998) assessed all four included Level II studies to be of
reasonable (Brigo and Serpellino, 1991; Straumsheim et al, 1997; Whitmarsh et al, 1993/1997) or
good (Walach et al, 1997) quality according to the Jadad scoring system and a separate assessment
of internal validity. In Brigo and Serpelloni (1991) there was a significantly greater number of patients
assessed as globally improved in the homeopathy group compared to placebo (p<0.001). However,
all other outcomes across the four included trials were either found to have non-significant
differences between treatment groups or the level of significance was not reported. Overall, Linde
and Melchart (1998) concluded, across all clinical conditions, that any evidence suggesting that
homeopathy has an effect over placebo is “not convincing because of methodological shortcomings
and inconsistencies”.
Evidence statement
Four systematic reviews of poor to good quality identified four randomised controlled trials (poor to
good quality; total of 295 participants, range: 60-98) that compared homeopathy with placebo for
the treatment of people with migraine or headache. LOC: Low.
Based on the body of evidence evaluated in this review homeopathy is not more effective than
placebo for the treatment of people with migraine or headache.
Table 41 Evidence summary table: the effectiveness of homeopathy for the treatment of migraine and headache
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
a
Level of Level of evidence population systematic review interpretation
a c
evidence Quality
b
Quality Sample size
Owen and Walach et al (1997) Patients with Individualised Placebo Frequency of Reduction in both homeopathic and There is insufficient evidence
Green (2004) [Level II] chronic homeopathy chronic headache placebo groups, no significant to support or refute the use
[Level I] 20-item assessment headache differences reported between groups of homeopathy for managing
AMSTAR: tool: 64.3% tension type, cervicogenic,
Intensity of Reduction in both homeopathic and or migraine headache – this
6/10 N=98
headache placebo groups, no significant is partially due to flaws in
differences reported between groups design.
SR of
homeopathy Severity of Reduction in both homeopathic and
for headache placebo groups, no significant "The present review concurs
headaches differences reported between groups with earlier studies and
indicates that the debate
Level of medication Reduction in both homeopathic and continues whether
used placebo groups, no significant homeopathy acts as a
differences reported between groups placebo or an effective
intervention.”
Whitmarsh et al Patients with Individualised Placebo Frequency of “Chance difference. Both groups
d
(1997) migraine homeopathy migraine improved”
[Level II]
Intensity of “Chance difference. Both groups
20-item assessment
migraine improved”
tool: 25.0%
N=60 Severity of “Chance difference. Both groups
migraine improved”
Straumsheim et al Patients with Individualised Placebo Frequency of Reduction in both homeopathic and
(1997) migraine homeopathy migraine placebo groups, no significant
[Level II] differences reported between groups
20-item assessment
Intensity of Reduction in both homeopathic and
tool: 57.1%
migraine placebo groups, no significant
N=73
differences reported between groups
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
a
Level of Level of evidence population systematic review interpretation
a c
evidence Quality
b
Quality Sample size
Brigo and Serpelloni Patients with Single dose 30c/4x Placebo Frequency of Homeopathy superior to placebo (p-
(1991) migraine in two weeks migraine value NR)
[Level II]
Intensity of Homeopathy superior to placebo (p-
20-item assessment
migraine value NR)
tool: 38.5%
N=60 Severity of Homeopathy superior to placebo (p-
migraine value NR)
Cucherat et Whitmarsh et al Patients with Individualised Placebo Change in mean No significant difference (p=0.83) “From the available
d
al (2000) (1993) headache homeopathy attack frequency evidence, it is likely that
[Level I] [Level II] over the course of among the tested
AMSTAR: Quality not formally the trial homeopathic treatments
10/11 assessed tested at least one shows an
N=64 added effect relative to
SR of placebo. The meta-analysis
homeopathy method used does not allow
for multiple any conclusion on what
conditions homeopathic treatment is
effective in which diagnosis
or against which symptoms.”
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
a
Level of Level of evidence population systematic review interpretation
a c
evidence Quality
b
Quality Sample size
more effective than placebo;
however, the strength of this
evidence is low because of
the low methodological
quality of the trials. Studies
of high methodological
quality were more likely to
be negative than the lower
quality studies. Further high
quality studies are needed to
confirm these results.”
Vernon et al Walach et al (1997) “About half Individualised Placebo NR “No difference between the two “No difference between the
(1999) [Level II] (of the 98 homeopathic groups on any important clinical two groups on any
[Level I] Quality: 86% (high subjects)” remedy for 12 variables related to headache activity” important clinical variables
AMSTAR: quality) had chronic weeks related to headache activity”
5/10 N=98 tension-type
headaches
SR of CAM
for headache
Linde and Straumsheim et al Patients with Individual Placebo Number of patients Intervention group: 8/35 (23%); The meta-analysis found an
Melchart (1997) migraine simillimum (if assessed globally Control group: 5/33 (15%). overall trend in favour of
(1998) [Level II] possible as improved Significance of inter-group differences homeopathy.
[Level I] Jadad score; internal constitutional) not reported The rate ratio was 1.62 (95% CI
f g 1.17, 2.23) and the odds ratio
AMSTAR: validity score: 3 ; 5 chosen from 60
available remedies Frequency of Similar decrease in both treatment was 2.62e
8/11 N=73
in D30, D200, or migraine groups The pooled rate ratio of the
1M and individual methodologically best studies
SR of Level of medication Similar decrease in both treatment was clearly smaller and not
homeopathy dosage used groups statistically significant (1.12,
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
a
Level of Level of evidence population systematic review interpretation
a c
evidence Quality
b
Quality Sample size
for multiple Walach et al (1997) Patients with Completely free Placebo Number of patients Trend in favour of placebo. 95% CI 0.87, 1.44)e
conditions [Level II] chronic individualised assessed globally Intervention group: 25/61 (41%); Similarly, the poor rate ratio of
headache homeopathy as improved Control group: 19/37 (51%). the six studies published in
Jadad score; internal
f g MEDLINE-listed journals was
validity score: 5 ; 6 treatment Significance of inter-group differences
not significantly different from
N=98 not reported placebo (1.22, 95% CI 0.94,
1.56)e
Frequency of Slight decrease in both groups
chronic headache
(Note: the meta-analysis
Level of medication Slight decrease in both groups included all conditions, not
used just migraine/headache)
Whitmarsh et al Patients with 11 homeopathic Placebo Number of patients No statistically significant inter-group
d
(1997) migraine remedies (patients assessed globally differences. Intervention group: 11/32
[Level II] were included as improved (34%); Control group: 5/31 (16%)
Jadad score; internal provided that the
f g simillimum was
validity score: 4 ; 4
N=63 among those) in
C30, two tablets,
twice weekly
Brigo and Serpelloni Patients with 8 homeopathic Placebo Number of patients Intervention group: 24/30 (80%);
(1991) migraine remedies (with assessed globally Control group: 4/30 (13%); p<0.001
[Level II] simillimum among as improved
Jadad score; internal the eight) in C30,
f g four doses in 2-
validity score: 3 ; 5
N=60 week intervals
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
d
Whitmarsh et al (1993) and Whitmarsh et al (1997) were the same study. The study was referred to as Whitmarsh et al (1993) in Cucherat et al (2000) and Whitmarsh et al (1997) in Owen and
Green (2004) and Linde and Melchart (1998).
e
Values >1 indicate results in favour of homeopathy, <1 in favour of placebo. If the 95% confidence interval does not fall below 1 the result is statistically significant.
f
The Jadad scale assesses the quality of published clinical trials based methods relevant to random assignment, double blinding and the flow of patients. The range of possible scores is zero
(bad quality) to 5 (good quality).
g
Internal validity score, maximum 6 points.
Evidence statement
One systematic review of good quality identified one very small randomised controlled trial (quality
not reported; 34 participants) that compared homeopathy (Caulophullum) with placebo for the
treatment of women with dystocia. LOC: Very low.
Based on only one very small study of unknown quality there is no reliable evidence on which to
draw a conclusion about the effectiveness of homeopathy compared to placebo for the treatment of
women with dystocia.
Table 42 Evidence summary table: the effectiveness of homeopathy for the treatment of dystocia
Study ID Included study Patient Intervention Comparator Outcome Results as reported in Systematic review
Level of Level of population the systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Cucherat (2000) Couldert (1981) Women with Caulophyllum 5 °C Placebo Success within 2 Significant difference in “It is clear that the strength
[Level I] [Level II] dystocia hours favour of homeopathy of available evidence is
AMSTAR: 10/11 Quality not (p=0.00055) insufficient to conclude that
specified homeopathy is clinically
SR of N=34 effective.”
homeopathy for
multiple (Note: this conclusion refers
conditions to all clinical conditions and
is not specific to dystocia)
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; C, centesimal; SR, systematic review.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
Evidence statement
One systematic review of medium quality identified two randomised controlled trials (poor quality;
40 and 93 participants) that compared homeopathy to placebo for the induction of labour or
reducing the duration of labour. LOC: Very low.
Based on the body of evidence evaluated in this review homeopathy is not more effective than
placebo for the induction of labour or reducing the duration of labour.
Table 43 Evidence summary table: the effectiveness of homeopathy for the induction of labour or reducing duration of labour in women
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
e
Smith (2010) Beer (1999) Women at 38-42 Caulophyllum D4, Placebo Caesarean section No significant difference “There is insufficient
[Level I] [Level II] weeks’ gestation doses were repeated (p=0.29) evidence to
e
AMSTAR: 8/10 Quality not high with prelabour hourly for 7 hours or RR 5.00 (95% CI 0.26, 98.00) recommend the use
N=40 rupture of until labour started of any homeopathic
Vaginal delivery not No significant difference
SR of membranes therapies as a
achieved within 24 (p=0.49)
homeopathy for method of induction
hours RR 0.33 (95% CI 0.01, 7.72)
induction of of labour.”
labour Augmentation with No significant difference
e
oxytocin (p=1.0)
RR 1.00 (95% CI 0.50, 1.98)
e
Instrumental delivery No significant difference
(p=1.0)
RR 1.00 (95% CI 0.54, 1.86)
e
Dorfman (1987) Women at 36 Five homeopathic Placebo Length of labour No significant difference
[Level II] weeks’ gestation. therapies: (p=0.91)
Quality not high
e Women were caulophyllum, Arnica, MD -0.40 (95% CI -7.21, 6.41)
N=93 excluded from the actea racemosa, e
Difficult labour Significant difference in favour
study if they had a pulsatilla and
poor obstetric geranium, with 3 of placebo
history, a current granules RR 0.28 (95% CI 0.12, 0.66)
history of administered
hypertension, morning and evening
diabetes, previous from 36 weeks’
caesarean section gestation. When
or cephalo-pelvic labour commenced,
disproportion the same dosage was
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
given every 15
minutes and stopped
after 2 hours or
sooner if the woman
was comfortable. No
details provided on
the precise dosage.
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; CI, confidence interval; D, decimal; MD, mean difference; RR, relative risk; SR, systematic review.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
d
The Jadad scale assesses the quality of published clinical trials based methods relevant to random assignment, double blinding and the flow of patients. The range of possible scores is zero
(bad quality) to 5 (good quality).
e
A formal quality assessment was not conducted. The author stated that the quality of the trials was “not high” and was difficult to assess because of insufficient detail in the research papers
and the small sample sizes provided inadequate power.
Table 44 Matrix indicating the studies that were included in the systematic reviews of ADHD
Study ID
Frei et al (2005) Jacobs et al Strauss (2000) Lamont (1997)
[Level II] (2005) [Level II] [Level III-1]
[Level II]
Davidson et al
(2011)
[Level I]
Heirs and Dean
Systematic review
(2009)
[Level I/III]
Altunc et al
(2007)
[Level I]
Linde and Melchart
(1998)
[Level I/III]
Davidson et al (2011) (AMSTAR score 8/10) was a systematic review of Level II studies that examined
the effectiveness of homeopathy for the treatment of psychiatric conditions, including ADHD. The
review included three Level II studies (Frei et al, 2005; Jacobs et al, 2005; Strauss, 2000) that
examined the effect of individualised homeopathy compared to placebo. All studies were rated by
the systematic review authors as “good” using the SIGN quality assessment tool. Frei et al (2005)
reported that homeopathy had a statistically significant benefit over placebo in terms of behavioural
and cognitive functions (p<0.05), using the Conners’ Global Index (parent-reported) to measure
efficacy. However, Jacobs et al (2005) found no significant difference between treatment groups
using the same primary outcome measure. Similarly, Strauss (2000) reported an effect in favour of
homeopathy that was “weak at best” based on one parent-reported outcome (Conners’ Parent
Symptom Questionnaire) and no significant difference compared to placebo based on one child
completed test (Children’s Checking Task). Overall, Davidson et al (2011) concluded that the mixed
results made it difficult to formulate a generalised conclusion for the clinical area as a whole.
Altunc et al (2007) (AMSTAR score 6/10) performed a systematic review to assess the efficacy of
homeopathy in nine childhood and adolescent conditions, including ADHD. The review included the
three Level II studies discussed above (Frei et al, 2005; Jacobs et al, 2005; Strauss, 2000), and no
additional outcomes were presented. The only additional information was that Altunc et al (2007)
reported a p-value of p=0.01 in favour of homeopathy for the Conners’ Parent Symptom
Questionnaire (Strauss, 2000), whereas Davidson et al (2011) had described the effect for this
outcome as “weak at best”. The actual magnitude of the effect, which is arguably more relevant, was
not discussed. The authors of the systematic review assessed the quality of the trials using a Jadad
score. Frei at el (2005) and Jacobs et al (2005) received scores of 5 and Strauss (2000) scored a 2.
Overall, Altunc et al (2007) concluded that there was “no compelling data” for any homeopathic
intervention for the treatment of ADHD due to a mixture of positive and negative results.
Heirs and Dean (2009) (AMSTAR score 11/11) conducted a Cochrane review of homeopathy for
ADHD or hyperkinetic disorder. The systematic review included the same three Level II studies that
investigated homeopathy in children with ADHD (Frei et al, 2005; Jacobs et al, 2005; Strauss, 2000),
plus a pseudo-randomised Level III-1 study (Lamont, 1997). Heirs and Dean (2009) assessed the
quality of each of the studies and considered aspects of methodological quality when they assessed
heterogeneity; however, no specific quality score was provided for each study. As shown in Table 45,
Heirs and Dean (2009) calculated standard mean differences (and 95% confidence intervals) to
demonstrate the effect of homeopathy compared to placebo when sufficient data were available.
The outcomes measured were stated more explicitly in Heirs and Dean (2009) than the other
systematic reviews, and the results of subscales within the overall scores were also provided. For
example, the Conners’ Parent Rating Scale is presented as a total score and also subscales including
hyperactivity, inattention, restlessness/impulsivity and emotional lability.
Heirs and Dean (2009) also reported the significant benefit of homeopathy over placebo according to
the Conners’ Global Index (parent-rated), as examined by Frei et al (2005). Individualised
homeopathy was also found be effective in reducing hyperactivity over ten days, compared to
placebo (standard mean difference: -0.65; 95% confidence interval: -1.27, -0.03) in the Level III-1
study conducted by Lamont (1997). However, no other significant intergroup differences were found
on any other outcomes (including subscales) across the four included studies. In the smallest,
poorest-quality Level II study by Strass (2000), half of the participants in both the intervention and
placebo arms received concomitant Ritalin.
Heirs and Dean (2009) also conducted a meta-analysis of the three Level II trials, despite the
“significant heterogeneity” that existed between them in terms of “how the ‘homeopathic
treatment’ was operationalised and implemented, as well as the effects”. The results of the meta-
analysis are presented in Table 46, and indicate that the pooling of results did not achieve any
positive effects in terms of standard mean difference.
Heirs and Dean (2009) acknowledged the major limitations of their systematic review and the
included studies. They suggested that the cross-over study design of Frei et al (2005) may have
affected the results; possibly through a regression to the mean in phase one, or alternatively a carry-
over effect in either phase one or two. The statistically significant benefit of homeopathy over
placebo (parent-rated Conners’ Global Index) reported in Frei et al (2005) may therefore be
attributable to flawed methodology. It was also noted that Frei et al (2005) included an initial
screening period to identify a subset of children who responded to homeopathy. An indefinite
number of follow-ups were allowed at this stage and medicines could be prescribed or changed until
a successful response was obtained. Participants who successfully responded to homeopathy (50%
amelioration of symptoms on Conners’ Global Index) were then entered into the Level II study.
In addition to the limitations of the included studies, Heirs and Dean (2009) acknowledged limitations
of their meta-analysis. The data pooled in the meta-analysis came predominantly from two studies
that adopted different homeopathic approaches, including formulaic (Strauss, 2000) and
individualised homeopathy (Jacobs et al, 2005). The authors felt that pooling was still appropriate
since “all of the studies could be interpreted as addressing the ongoing controversy of whether
homeopathic dilutions have any effect over a placebo dose”. Nonetheless, Heirs and Dean concluded
that there is “currently little evidence for the efficacy of homeopathy” and “insufficient evidence to
recommend the use of homeopathy for children diagnosed with ADHD”.
Finally, an earlier systematic review by Linde and Melchart (1998) (AMSTAR score 8/11) examined
the efficacy of individualised homeopathy for the treatment of a variety of clinical conditions. The
Level III-1 study of children with ADHD by Lamont (1997) was identified for inclusion in the
systematic review; however, it was excluded from the meta-analysis due to “insufficient reporting of
results” and a “problematic design” in which observation periods were not standardised. Lamont
(1997) found a significantly better “mean response score” (t=2.16; p<0.05) in the homeopathy group
(1.00) compared with placebo (0.35). Overall, Linde and Melchart (1998) concluded that, across all
clinical conditions, any evidence suggesting that homeopathy has an effect over placebo is “not
convincing because of methodological shortcomings and inconsistencies”.
Evidence statement
Four systematic reviews of medium to good quality identified three randomised controlled trials
(good quality; total of 125 participants, range: 20-62) and one very small prospectively designed,
non-randomised controlled study (poor quality; 45 participants) that compared homeopathy with
placebo for the treatment of children with attention deficit/hyperactivity disorder (ADHD).
These studies are of insufficient quality and/or size to warrant further consideration of their findings.
LOC: Very low - low.
Based on the body of evidence evaluated in this review there is no reliable evidence that
homeopathy is more effective than placebo for the treatment of children with ADHD.
Table 45 Evidence summary table: the effectiveness of homeopathy for the treatment of children with attention deficit/hyperactivity disorder
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Davidson et Frei et al (2005) Children with Individualised Placebo CGI-P Statistically significant benefit for Overall there were mixed
al (2011) [Level II] ADHD homeopathy homeopathy, particularly in results for the efficacy of
[Level I] SIGN rating: behavioural and cognitive functions homeopathy on ADHD,
AMSTAR: Good (p<0.05). making it difficult to
8/10 N=62 generalise the results to
this clinical area.
Jacobs et al Children with Individualised Placebo CGI-P Placebo tended to be better than
SR of
(2005) ADHD homeopathy homeopathy, but not significantly
homeopathy
[Level II] better
for multiple
conditions SIGN rating:
Good
N=43
Strauss (2000) Children with Individualised Placebo CPSQ Overall hyperactivity improved more
[Level II] ADHD homeopathy on homeopathy than placebo;
e
SIGN rating: however effect was weak at best
Good
d CCT No significant difference between
N=20 homeopathy and placebo
Altunc et al Frei et al (2005) Children with Individualised Placebo CGI-P Significant difference “The best evidence from
(2007) [Level II] ADHD homeopathy, material (p=0.048) double-blind RCTs shows
j
[Level I] Jadad score 5 89% male potencies, 6 weeks, no compelling data for any
treatment regimen not Adverse events Main adverse events causing therapeutic or preventive
AMSTAR: N=62
reported
f withdrawal were 1 increasing tics, 2 intervention testing
6/10
behavioural disorders, 1 reactive homeopathy for childhood
depression and adolescence
SR of
homeopathy Jacobs et al Children with Individualised Placebo CGI-P No significant difference ailments.”
for multiple (2005) ADHD homeopathy, 18
conditions [Level II] Mean age: 9.5 weeks, homeopathic “The evidence for ADHD…
j years remedies prescribed Adverse events No adverse events is mixed, showing both
Jadad score 5
77% male with no limit, doses positive and negative
N=43
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
and potencies not results for [the] main
g
reported outcome measure.”
Heirs and Frei et al (2005) Children with Individual Placebo CGI-P Significant benefit of homeopathy over “Overall this review found
Dean (2009) [Level II] ADHD homeopathic medicine placebo in the cross-over. Generic no evidence that
[Level I/III] Quality score not aged 7-15 yr – prescribed according inverse weighted average treatment homeopathy has a
AMSTAR: specified symptoms had to Hahnemann and effect: significant impact on the
11/11 N=62 improved by Bönninghausen, -1.67 (95% CI -3.32, -0.02) overall severity, core
≥50% under administered as daily symptoms or related
homeopathic liquid doses (LM Inattention and Insufficient data to calculate effect size outcomes of children
SR of treatment impulsivity (using
homeopathy potencies) diagnosed with Attention
during TAP)
for ADHD screening Deficit Hyperactivity
Disorder.”
Jacobs et al Children with Individual Placebo CGI-P No evidence for effectiveness of
(2005) ADHD homeopathic medicine homeopathy over placebo. Significant heterogeneity
[Level II] mean age: 9 – prescribed according SMD 0.13 (95% CI -0.47, 0.73) exists between the three
Quality score not years to Hahnemann and
CPRS-R No evidence of effectiveness of trials included in the meta-
specified Bönninghausen, analysis in terms of how
administered as daily homeopathy over placebo.
N=43 “homeopathic treatment”
liquid doses (LM SMD 0.17 (95% CI -0.43, 0.77)
was operationalised and
potencies) implemented as well as the
Hyperactivity No evidence of effectiveness of
subscale from homeopathy on hyperactivity effects (one used a
CPRS-R symptoms. formula of medicines given
SMD 0.21 (95% CI -0.39, 0.81) without individualisation
to patients over a relatively
CPRS-R domain of No evidence of effectiveness was short period of time; one
inattention found.
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
SMD 0.39 (95% CI -0.21, 1.00) used a form of
individualised homeopathy
Restlessness/ No significant evidence of similar to how ‘classical’
impulsivity (from effectiveness. homeopathy is used in
the CPRS-R) SMD 0.02 (95% CI -0.57, 0.62) practice with freedom to
Conduct/ No evidence of effectiveness. vary the medicines as well
oppositional as potency (strength) and
SMD 0.10 (95% CI -0.50, 0.70)
behaviour frequency, although critics
have suggested that the
Emotional Lability No evidence of effectiveness. treatment period of 18
domain (from the SMD 0.21 (95% CI -0.39, 0.81) weeks was too short to
CPRS-R) show benefit hence the
negative findings).
Global total on the No significant differences. However, “a trial of
CGI-T SMD 0.41 (95% CI -0.20, 1.01) individualised homeopathy
Restless/ Impulsive No significant differences. with minimised non-
behaviour (sub- specific effects found a
SMD 0.39 (95% CI -0.21, 1.00)
domain of CGI-T) significant benefit from
homeopathy” (Frei et al
Emotional Lability No significant differences. 2005)
(sub-domain of SMD 0.41 (95% CI -0.19, 1.02)
CGI-T) “There is insufficient
evidence to draw robust
Inattention No significant difference.
conclusions about the
(measured by the SMD -0.12 (95% CI -0.72, 0.48)
effectiveness of any
Conners’ CPT)
particular form of
Impulsivity No evidence of effectiveness. homeopathy for ADHD at
(measured by the SMD -0.07 (95% CI -0.67, 0.53) present given that only
CPT) three randomised
controlled trials have been
Strauss (2000) Children with Formula homeopathic Placebo, with CRS (older version No evidence of effectiveness of carried out, and all were
h
[Level II] ADHD combination medicine (n=5) or which included a homeopathy on ADHD Index score as relatively small in size.”
Quality score not aged 7-10 – ten drops, three without domain termed the rated by parents.
years times daily for two Hyperactivity Index
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
specified half (n=10) months, with (n=5) or Ritalin (n=5) but has been SMD -0.17 (95% CI -1.05, 0.71) “There is at present
N=20 taking Ritalin without Ritalin (n=5) renamed the ADHD insufficient evidence to
18 boys; 2 girls Index in later recommend the use of
revisions) homeopathy for children
diagnosed with ADHD.”
Lamont (1997) Children with Individualised Placebo Change in Effectiveness was found.
[Level III-1] ADHD homeopathic medicine hyperactivity over SMD -0.65 (95% CI -1.27, -0.03)
Quality score not all lived in – prescribed following 10 days (measured
specified foster homes a consultation using by a five point
mean age 10 classical homeopathic rating scale
N=43
years prescribing and the completed by
35% Black, RADAR repertory parents)
47% Hispanic;
software.
18% Caucasian
Administered as 6 x
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
200c pills daily for up
to 5 days. Ten days
after the prescription
progress was followed-
up, with the option of
changing the medicine
on two further
occasions.
Linde and Lamont (1997) Children with Individual simillimum Placebo Mean response Response scores in homeopathy group The authors did not
Melchart [Level III-1] ADHD in C200 daily up to 5 score significantly better (mean scores 1.00 provide any specific
(1998) Quality: 2,2
i mean age 10 days, computer- vs 0.35; t=2.16; p<0.05 conclusions regarding the
[Level I/III] N=45 years assisted (RADAR) efficacy of homeopathy in
AMSTAR: children with ADHD.
8/11
SR of
homeopathy
for multiple
conditions
Abbreviations: ADHD, attention deficit/hyperactivity disorder; AMSTAR, Assessment of Multiple Systematic Reviews; CCT, Children’s Checking Task; CGI-P, Conners’ Global Index-Parent; CPRS-
R, Revised Conners’ Parent Rating Scale; CPSQ, Conners’ Parent Symptom Questionnaire; NR, not reported; SIGN, Scottish Intercollegiate Guidelines Network; SR, systematic review; TAP, Test
battery for Attention Performance.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
d
Refers to the number of participants who completed the study. Number of participants enrolled was not reported.
e
Subsequent review in Cochrane analysis failed to find significance on any measure.
f
17 different remedies prescribed, potencies between Q3 and Q42: Calcarea carbonica, sulphur, Chamomilla, Lycopodium, silica, Hepar-sulph., Nux vomica, China, Ignatia, Mercurius, Capsicum,
Causticum, Hyoscyamus, phosphorous, phosphoric acid, sepia, Staphysagria
g
41 different remedies prescribed: Medorrhinum, Saccharum officinalis, Calcarea carbonica, Calcarea phosphorica, China officinalis, stramonium; Concomitant treatment: stimulant
medications (5H; 4P)
h
Remedy contains selenium in 10X, 15X, 30X, 200X with potassium phosphate in 2X, 10X, 30X, 200X. This combination is sold commercially to improve concentration, memory and alertness.
i
Quality was assessed using (i) Jadad score, out of five; (ii) internal validity score, out of six.
j
The Jadad scale assesses the quality of published clinical trials based methods relevant to random assignment, double blinding and the flow of patients. The range of possible scores is zero
(bad quality) to 5 (good quality).
Table 47 Matrix indicating the studies that were included in the systematic reviews of anxiety or stress-related
disorders
Systematic review
Pilkington et al (2006) Davidson et al (2011)
[Level I] [Level I]
Ngobese (2006)
[Level II]
Thompson (2005)
[Level II]
Vaithilingam (2005)
[Level II]
Baker (2003)
[Level II]
Bonne (2003)
[Level II]
Study ID
Traub (2000)
[Level II]
McCutcheon (1996)
[Level II]
Alibeu (1992)
[Level II]
Hariveau (1991)
[Level II]
Heulluy (1985)
[Level II]
Stanton (1981)
[Level II]
Pilkington et al (2006) (AMSTAR score 8/10) performed a systematic review of the clinical evidence
on homeopathy for the treatment of anxiety and anxiety disorders. It included the results of eight
Level II studies of variable quality.
Test anxiety was assessed in two Level II studies (Stanton, 1981; Baker, 2003). Stanton (1981) was a
placebo-controlled trial that examined the effect of a homeopathic preparation for test anxiety in 40
subjects. The study found a significant reduction in test anxiety (as measured by the Test Anxiety
Scale (TAS)) in the homeopathy group compared with placebo. Pilkington et al (2006) noted,
however, that “the original article was unavailable so that it was not possible to rate the quality”.
Baker (2003) (Jadad score of 4) was an attempt to replicate the study by Stanton (1981). The Level II
study was conducted in an Australian University with 70 test anxious student volunteers. A revised
version of the TAS was used, and the results found no significant difference in test anxiety between
the homeopathy and placebo groups. A comparison of the results with the data by Stanton (1981)
suggested that anxiety scores pre-treatment “might have been slightly higher” in the 1981 study;
however, it was not clear whether the higher baseline anxiety scores related to the homeopathy or
placebo treatment arm or the mean score across both groups.
Moderate anxiety or generalised anxiety disorder was assessed in two Level II studies (McCutcheon,
1996; Bonne, 2003). McCutcheon (1996) (Jadad score of 4) found no significant differences in either
pre- or post-test State-Trait Anxiety Inventory (STAI) scores between the homeopathy and placebo
groups. The homeopathy group, however, reported significantly less loss of sleep. The author
concluded that “the homeopathic complex used may be useful for this aspect of anxiety, although it
appeared to have little value in the reduction of either state or trait anxiety”. Bonne (2003) (Jadad
score of 3) reported no significant differences between adults with generalised anxiety disorder who
were treated with individualised homeopathic remedies or placebo for 10 weeks. In fact, a significant
improvement was observed in both the active and placebo groups. Pilkington et al (2006) noted,
however, that this study may have been underpowered as a power calculation demonstrated that a
minimum of 60 participants were required but only 44 were recruited.
Mixed anxiety and depressive disorder was assessed in two Level II studies of “proprietary
homeopathic complexes” (Hariveau, 1991; Heulluy, 1985). Both Level II studies were rated a Jadad
score of 1. The comparator arm for both studies used benzodiazepine, which primarily comprises an
anxiolytic and thus the anxiety component of the condition was being treated in the comparator
group. In both Level II studies, the homeopathic complex was reported to be as effective as
benzodiazepine, but this may be a result of the studies being insufficiently powered to detect a
difference. Pilkington et al (2006) also reported that “concerns over the initial diagnosis of
participants together with a lack of detail about the methodology and outcome measures limit the
usefulness of these findings”.
Finally, anxiety associated with medical or physical conditions was assessed in two Level II studies
(Alibeu, 1992; Thompson, 2005). Alibeu (1992) (Jadad score of 2) was a Level II study of homeopathic
aconite for postoperative agitation in children. The results suggested that homeopathic aconite
might be an appropriate treatment as “95% good results” were reported. However, Pilkington et al
(2006) noted that “no clear objective outcome measures were provided and many of the
methodological details such as randomisation, allocation concealment and blinding were unclear”. In
contrast, Thompson (2005) (Jadad score of 5) was a “rigorously conducted randomised placebo-
controlled trial” of homeopathy for the treatment of symptoms of oestrogen withdrawal (including
anxiety) in 53 breast cancer patients. The authors reported that both groups experienced clinically
important improvements based on Measure Yourself Medical Outcome Profile (MYMOP) scores over
the 16 week trial period. However, the study did not find that the specific effect of the remedy added
further to the non-specific effects of the consultation, possibly due to lack of power.
Overall, the systematic review by Pilkington et al (2006) concluded that the Level II studies reported
contradictory results and “the findings of many of the included studies were limited by the lack of
detail about methodology and outcome measures as well as concerns that several of the studies
were insufficiently powered to detect differences between treatments”. Consequently, “no firm
conclusions on the efficacy of homeopathy for anxiety can be drawn”.
Davidson et al (2011) (AMSTAR score 8/10) was a systematic review of Level II studies of
homeopathy for psychiatric conditions. For anxiety or stress-related conditions, six Level II studies
were identified. Three Level II studies (Baker, 2003; Bonne, 2003; McCutcheon, 1996) overlapped
with those identified in Pilkington et al (2006). The interpretation of those studies was consistent
between the two systematic reviews.
Davidson et al (2011) also included three additional Level II studies that were not identified in
Pilkington et al (2006): Ngobese (2006), Vaithilingam (2005) and Trabu (2003). Ngobese (2006) was
reported to be a fair quality Level II study that investigated the effect of individualised homeopathy
in patients with generalised anxiety disorder. The study reported no significant difference between
the homeopathy and placebo groups for any outcome measure. Vaithilingam (2005) was a poor-
quality Level II study that assessed individualised homeopathy in patients with job-related burnout.
The results were that “homeopathy was worse than placebo on the depersonalisation scale of
Maslach Burnout Inventory”. Finally, Trabu (2003) was a poor-quality study that examined a
combined three-remedy product in patients with test anxiety. While the outcome measure was
unclear, Davidson et al (2011) reported “no effect on the total scores of the primary measures” and
“weak evidence for homeopathy on scale items”. Overall, Davidson et al (2011) concluded that there
is “no support for the efficacy of homeopathy in anxiety- or stress-related conditions”.
Reviewer comments
Conflicting evidence exists for the effectiveness of homeopathic treatments in patients with anxiety or
stress-related conditions. Many of the Level II studies that have investigated this indication are small
in size and limited by poor methodological quality. The evidence reviewer notes that Pilkington et al
(2006) also included one uncontrolled study (Davidson, 1997) in their assessment of anxiety and
anxiety disorders. However, this study was excluded for the purposes of this overview as it is classed
as Level III-3 evidence.
Evidence statement
Two systematic reviews of medium quality identified nine randomised controlled trials (poor to good
quality; total of 402 participants, range: 27-77) that compared homeopathy with placebo for the
treatment of people with anxiety or stress-related conditions. LOC: Very low - low.
Based on the body of evidence evaluated in this review homeopathy is not more effective than
placebo for the treatment of people with anxiety or stress-related conditions.
Two systematic reviews of medium quality identified three randomised controlled trials (poor to
medium quality; total of 172 participants, range: 28-84) that compared homeopathy with other
therapies (lorazepam, diazepam and cognitive behavioural therapy) for the treatment of people with
anxiety or stress-related conditions.
These studies are of insufficient quality and/or size to warrant further consideration of their findings.
LOC: Very low - low.
Based on the body of evidence evaluated in this review there is no reliable evidence that
homeopathy is as effective as the other therapies for the treatment of people with anxiety or stress-
related conditions.
Table 48 Evidence summary table: the effectiveness of homeopathy for the treatment of anxiety or stress-related conditions
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Pilkington et Thompson (2005) Breast cancer Individualised Placebo Mean HADS anxiety No significant difference The findings of many of
al (2006) [Level II] patients with prescribing (60 scores the included studies
d
[Level I] Jadad score 5 symptoms of minute initial were limited by the lack
oestrogen consultation plus MYMOP No significant difference of detail about
AMSTAR: N=53
8/10 withdrawal four 20 minute Menopausal Significant clinical improvements in methodology and
(including follow-up Symptom both groups; between-group outcome measures as
SR of anxiety) consultations, over Questionnaire differences not clear (p-value NR) well as concerns that
homeopathy 16 weeks) several of the studies
for anxiety EORTC QLQ-C30 Significant clinical improvements in were insufficiently
both groups; between-group powered to detect
differences not clear (p-value NR) differences between
treatments
Baker (2003) Australian Traditionally Radionically Benson Revised No significant difference
[Level II] university prepared Argentum prepared Test Anxiety Scale
d No firm conclusions on
Jadad score 4 students with nitricum 12x, twice Argentum
TAS 36-item No significant difference the efficacy of
N=70 test anxiety daily for 4 days nitricum 12x;
Argentum nitricum homeopathy for anxiety
(score of 50+ on or placebo
questionnaire pre- can be drawn
Benson RTA) (alcohol/water
mixture as per and post-treatment
treatments) (1 week later)
Bonne (2003) Adults with Individualised Placebo (non- HAM-A; HAM-D; Significant improvement in both
[Level II] generalised homeopathy (single medication BSI; PGWBI; BDI; groups (p-value NR)
d
Jadad score 3 anxiety disorder remedy, all dilutions impregnated STAI subjective No significant difference between
-30
N=44 (DSM-IV >10 ) for 10 weeks globules) distress (VAS) groups
diagnosis);
HAM-A >20,
HAM-D <18
e
McCutcheon (1996) Students with Anti-Anxiety , 20 Placebo STAI No significant difference
[Level II] above average drops, four times
Resting pulse rate No significant difference
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
d
Jadad score 4 anxiety scores daily for 15 days Sleep loss Significantly less sleep loss in the
N=77 (score of 18+ on homeopathy group
f
part one of pre- (p-value NR)
test STAI)
Alibeu (1992) Children (aged 6 Aconite Placebo Physician-assessed “Effective with 95% good results”
[Level II] months to 14 improvement
d
Jadad score 2 years) with post-
N=50 operative
agitation/anxiety
Hariveau (1991) Patients with Lithium Microsol, 3-4 Lorazepam 2- Sleep – measure Unclear
[Level II] reactive anxiety ampoules per day, 4mg per day, not stated
d
Jadad score 1 depression twice daily for 30 twice daily
days Delay in sleep onset Unclear
N=84
– measure NR
“Emotionalism” – Unclear
measure not stated
Heulluy (1985) Patients under Non-individualised Diazepam Ratio of pre and No difference – L72 as effective as
[Level II] consultation for L72 (constituents not (dose and post scores for diazepam on all measures
d
Jadad score 1 depression, specified), 20 drops, frequency selected items on
N=60 postmenopausal four times daily for unknown) HAM scale – details
involution or 31 days. Dose not specified
thymo-effective increased if required
dystonia Adverse events - 1 patient treated with L72 and two
drowsiness treated with diazepam suffered
from drowsiness
Stanton (1981) Patients with test Argentum nitricum Placebo Test Anxiety Scale Homeopathic preparation
[Level II] anxiety 12x significantly improved test anxiety
Quality not compared with placebo
specified (p-value NR)
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
N=40
Davidson et Ngobese (2006) Patients with Individualised Placebo or HARS, BAI, PPQ No significant difference There is no support for
al (2011) [Level II] GAD homeopathy CBT “A proven treatment for GAD, cognitive efficacy of homeopathy
[Level I] SIGN score: fair therapy, failed to work; study can be in anxiety- or stress-
AMSTAR:8/10 N=41 regarded as a “failed” study rather than related conditions.
a negative study for homeopathy. In
other words, it is not informative.
SR of Length of treatment may have been
homeopathy inadequate”.
for multiple
Vaithilingam (2005) Patients with job- Individualised Placebo Maslach Burnout Homeopathy worse than placebo
conditions
[Level II] related burnout homeopathy Inventory subscales on depersonalisation scale of
SIGN score: poor Maslach Burnout Inventory
g
N=30
Baker et al (2003) Patients with test Argentum nitricum Placebo Benson Revised Results favoured placebo (weak
[Level II] anxiety Test Anxiety Scale effect size)
SIGN score: fair
g
N=62
Bonne et al (2003) Patients with Individualised Placebo Rate of response No significant differences (“results
[Level II] GAD homeopathy unlikely to be different with a
SIGN score: fair larger sample size”)
N=44 Homeopathy 40% vs. control 42%
Traub (2000) Patients with test Combined 3-remedy Placebo Unclear No effect on the total scores of the
[Level II] anxiety product primary measures. Weak evidence
SIGN score: poor for homeopathy on scale items
g
N=32
McCutcheon (1996) Patients with Combined 9-remedy Placebo STAI(T), STAI(S), Mixed results; significant
[Level II] high trait anxiety product sleep, pulse improvement on sleep, but no
SIGN score: fair benefit on state anxiety
N=77
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; BDI, Beck Depression Inventory; BSPS, Brief Social Phobia Scale; BSI, Brief Symptom Inventory; CBT, cognitive behavioural
therapy; DSM, Diagnostic and Statistical Manual; EORTC QLQ, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire; GAD, generalised anxiety disorder;
HADS, Hospital Anxiety and Depression Scale; HAM, Hamilton Rating Scale for Anxiety; ITT, intention-to-treat; MYMOP, Measure Yourself Medical Outcome Profile; NR, not reported; PGWBI,
Psychological General Well-Being Index; SIGN, Scottish Intercollegiate Guidelines Network; SR, systematic review; STAI, State-Trait Anxiety Inventory; TAS, Test Anxiety Scale.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
d
The Jadad scale assesses the quality of published clinical trials based methods relevant to random assignment, double blinding and the flow of patients. The range of possible scores is zero
(bad quality) to 5 (good quality).
e
Constituents include: Cicuta virosa, Ignatia, Gaultheria, Asafoetida, Corydalis, Sumbulis, Valeriana officinalis, Hyoscyamus, Avena sativa.
f
Authors of SR state that sleep disturbance is not a core symptom of anxiety.
g
Number of patients enrolled was not reported. The sample size refers to the number of patients who completed the study.
Evidence statement
One systematic review (2006) did not identify any prospectively designed and controlled studies that
assessed the effectiveness of homeopathy in people with borderline personality disorder.
4.12.4 Dementia
The effectiveness of homeopathy for the treatment of patients with dementia was assessed in one
systematic review (McCarney et al, 2009; AMSTAR score 5/5). This Cochrane review aimed to
evaluate the effectiveness and safety profile of homeopathically prepared medications used in
treating dementia, as established by Level II studies. The results of the literature search conducted in
March 2009 identified no studies that fulfilled the criteria for inclusion. The authors thus concluded
that “in view of the absence of evidence it is not possible to comment on the use of homeopathy in
treating dementia”.
Evidence statement
One systematic review (2009) did not identify any prospectively designed and controlled studies that
assessed the effectiveness of homeopathy in people with dementia.
4.12.5 Depression
The effectiveness of homeopathy for the treatment of depression was assessed in one systematic
review (Pilkington et al, 2005; AMSTAR score 7/10) as summarised in Table 49. The systematic
review, which focused specifically on the effectiveness of homeopathy for the treatment of
depression, identified two Level II studies (Katz et al, 2005; Heulluy, 1985) and five uncontrolled
studies that did not meet the standards for inclusion in this review. The systematic review did not
identify any Level II, Level III-1 or Level III-2 studies that compared homeopathy to placebo for the
treatment of depression.
The formal quality assessment was not specified for each individual trial by Pilkington et al (2005),
although the authors did comment on the low methodological quality of the two Level II studies as
well as the very small number of patients that were recruited (4 and 30 patients, respectively). In
addition, Pilkington et al (2005) questioned whether Heulluy (1985) had used an appropriate
comparator, stating “the use of an anxiolytic drug as a control appears inappropriate in a trial in
patients with depression”.
Ultimately, no results were presented from Katz et al (2005) due to low recruitment (4 patients) and
the findings of the systematic review are largely based on the flawed Level II study by Heulluy (1985),
which reported no difference between homeopathy (L72) and diazepam in terms of the ratio of pre-
and post-treatment scores for selected items on the Hamilton Depression Scale. The systematic
review authors conclude that the evidence base for homeopathy in depression is currently weak due
to the “lack of clinical trials of high quality”.
Reviewer comments
Overall, the findings of the systematic review were limited by the low recruitment and methodological
flaws within the included trials. The identification of only two very small Level II studies (one of which
presented no results due to low recruitment), prevented the authors of the systematic review from
presenting any strong evidence to indicate benefit or inferiority of homeopathy compared to other
interventions.
The evidence reviewer supports the assertion by Pilkington et al (2005) that the studies identified in
their review were inadequately randomised, controlled and powered in order to meet conventional
measures of quality from which any meaningful clinical evidence could be drawn.
Evidence statement
One systematic review (2005) did not identify any prospectively designed and controlled studies that
assessed the effectiveness of homeopathy compared with placebo for the treatment of people with
depression.
One systematic review of medium quality identified two randomised controlled trials (poor quality; 4
and 30 participants) that compared homeopathy with diazepam or fluoxetine for the treatment of
people with depression.
These studies are of insufficient quality and size to warrant further consideration of their findings.
LOC: Very low.
Based on the body of evidence evaluated in this review there is no reliable evidence that
homeopathy is as effective as diazepam or fluoxetine for the treatment of people with depression.
Table 49 Evidence summary table: the effectiveness of homeopathy for the treatment of depression
Study ID Included study Patient Intervention Comparator Outcome Results as reported in Systematic review
Level of Level of population the systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Pilkington et al Katz et al (2005) Patients with Homeopathic Fluoxetine – 20 HAMD score No results reported due to “Evidence for the
(2005) [Level II] major depressive remedy selected mg daily CGI low recruitment effectiveness of homeopathy
[Level I] Low quality episodes of from a list of 30 increased to 40 SF-12 in depression is limited due
AMSTAR: 7/10 N=4 moderate severity remedies by a mg after 4 weeks to lack of clinical trials of
QoL questionnaire
(HAMD score 17+) trained if no high quality.”
WSDS
SR of homeopath improvement in
(using decision HAMD score, or Pittsburgh Sleep
homeopathy for “Further research is
support software) placebo matched Quality Index required, and should include
depression
tablets or questionnaire well-designed controlled
capsules Treatment studies with sufficient
Credibility Side numbers of participants.”
Effects checklist
Heulluy (1985) Patients currently L72 (constituents Diazepam – dose Ratio of pre and post No difference – L72 as “The evidence base is
[Level II] under not specified) – and frequency scores for selected effective as diazepam currently weak.”
Low quality consultation for 20 drops, 4 times unknown items on HAMD scale
N=30 depression, daily for 31 days,
postmenopausal dose increased if
involution or required
thymo-effective
dystonia
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; CGI, Clinical Global Improvement; HAMD, Hamilton Depression Scale; QoL, quality of life; SF-12, Short Form-12; SR,
systematic review; WSDS, Work and Social Disability Scale.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
Evidence statement
One systematic review of medium quality identified one small prospectively designed and controlled
study (poor quality; 60 participants) that compared homeopathy (Simillimum) with placebo for the
treatment of people with a heroin addiction. LOC: Very low.
Based on only one small poor quality study there is no reliable evidence on which to draw a
conclusion about the effectiveness of homeopathy compared to placebo for the treatment of people
with a heroin addiction.
Table 50 Evidence summary table: the effectiveness of homeopathy for the treatment of heroin addiction
Study ID Included study Patient population Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Linde and Bakshi (1990) Patients with a heroin Individual Placebo Unclear “Homeopathy superior to “Totally insufficient report –
Melchart (1998) [Level II or Level addiction simillimum placebo.” completely inassessible.”
d
[Level I/III] III-1]
e
AMSTAR: 8/11 Quality: 1, 2
N=60
SR of homeopathy
for multiple
conditions
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; SR, systematic review.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
d
The study was either randomised or pseudo-randomised; however, the allocation of participants was not described.
e
Quality assessed using (i) Jadad score (out of 5); (ii) internal validity score (out of 6)
Table 51 Matrix indicating the studies that were included in the systematic reviews of premenstrual syndrome
Study ID
Laister (2008) Yakir et al Chapman et al Kirtland Yakir et al
[Level II] (2001) (1994) (1994) (1994)
[Level II] [Level II] [Level II] [Level II]
Davidson et al
(2011)
Systematic review
[Level I]
Stevinson and
Ernst (2001)
[Level I]
Linde and
Melchart (1998)
[Level I]
The systematic review by Davidson et al (2011) (AMSTAR score 8/10) analysed all Level II studies of
homeopathy for psychiatric conditions. Four Level II studies were identified for the PMS indication.
Laister (2008) (good quality), Yakir et al (2001) (fair quality), and Chapman et al (1994) (fair quality)
were all Level II studies that investigated the effect of individualised homeopathy in women with
PMS. The results of a Menstrual Distress Questionnaire (MDQ) in Yakir et al (2001) were “suggestive
of greater benefit for homeopathy”; however the systematic reviewer noted the limitation of the
small trial sample size (N=23). Laister (2008) found that “homeopathic simillimum was not effective
in treating PMS”. Chapman et al (1994) found that there was no significant difference in the rate of
response between the homeopathy and placebo groups. Indeed, a high placebo response rate of 60%
was noted. Kirtland (1994) was a poor-quality Level II study that examined the effect of homeopathic
Folliculinum compared with placebo in women with PMS. The results of a MDQ and Premenstrual
Assessment Form “suggested an effect for homeopathy”; however, no further details were provided.
Overall, Davidson et al (2011) concluded that there is “little evidence of homeopathy for
premenstrual problems, other than the one study with a small sample size”.
Stevinson and Ernst (2001) (AMSTAR score of 6/10) conducted a systematic review that aimed to
determine whether the use of complementary and alternative therapies for PMS is supported by
evidence of effectiveness from rigorous clinical trials. The literature search identified one relevant
Level II study (Chapman et al, 1994) for the homeopathy intervention. The authors commented that
“a placebo response of 47% in the pre-treatment phase illustrates the powerful effect of placebo on
premenstrual symptoms and suggests that the depth and empathy of the homeopathic interview
may have a therapeutic effect”. Whilst the quality of Chapman et al (1994) was not specified,
Stevinson and Ernst (2001) stated that “although it was rigorously designed, the selection criteria
were so strict that only 10 of the 205 women screened actually participated. The lack of statistical
power renders the results inconclusive”. Consequently, Stevinson and Ernst (2001) concluded that
“the current evidence for homeopathy is not particularly promising, with trial results indicating little
more than a placebo response”.
Linde and Melchart (1998) (AMSTAR score 8/11) performed a systematic review that examined the
efficacy of individualised homeopathy on a variety of clinical conditions. The authors identified two
Level II studies (Chapman et al, 1994; Yakir et al, 1994) for the PMS indication. Similar to all of the
above systematic reviews, Linde and Melchart (1998) also reported that the homeopathy and
placebo groups experienced a similar response in Chapman et al (1994). Whilst a Jadad score of 4
was given, it was noted that Chapman et al (1994) was a well-planned trial but “recruitment failed
completely – totally insufficient sample size”. In the second included Level II study (Yakir et al, 1994),
Linde and Melchart (1998) observed that there was “greater improvement in homeopathy group”.
However, the significance of inter-group differences was not stated. A quality assessment of Yakir et
al (1994) was not performed as the report was only available as an abstract. Linde and Melchart
(1998) did not formulate a conclusion about the effect of homeopathy for the treatment of women
with PMS.
Evidence statement
Three systematic reviews of medium quality identified five randomised controlled trials (poor to
good quality; total of 103 participants, range: 10-39) that compared homeopathy with placebo for
the treatment of women with premenstrual syndrome. LOC: Very low - low.
Based on the body of evidence evaluated in this review homeopathy is not more effective than
placebo for the treatment of women with premenstrual syndrome.
Table 52 Evidence summary table: the effectiveness of homeopathy for the treatment of premenstrual syndrome
Study ID Included study Patient Intervention Comparator Outcome Results as reported in Systematic review
Level of Level of population the systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Davidson et al Laister (2008) Women with Individualised Placebo MDQ Homeopathic simillimum “Little evidence of efficacy
(2011) [Level II] premenstrual homeopathy not effective in treating of homeopathy for
[Level I] Good quality syndrome PMS premenstrual problems,
AMSTAR: 8/10 N=39 other than in one study with
a small sample size.”
Yakir et al (2001) Women with Individualised Placebo MDQ Suggestive of greater
SR of
[Level II] premenstrual homeopathy benefit for homeopathy,
homeopathy
Fair quality syndrome but small sample size
for multiple
conditions N=23
Kirtland (1994) Women with Folliculinum 15C Placebo Each item on MDQ, PAF Suggests an effect for
[Level II] premenstrual homeopathy
Poor quality syndrome
N=31
Stevinson and Chapman et al Not reported. Homeopathy, 3 Placebo Diary “A placebo response of “The current evidence for
Ernst (2001) (1994) Assumed to be doses monthly for 47% in the pretreatment homeopathy is not
[Level I] [Level II] women with 4 cycles washout phase illustrates particularly promising, with
AMSTAR: 6/10 Quality not premenstrual the powerful effect of trial results indicating little
specified syndrome placebo on premenstrual more than a placebo
SR of CAM for N=10 symptoms and suggests response.”
PMS that the depth and
empathy of the
homeopathic interview
may have a therapeutic
Study ID Included study Patient Intervention Comparator Outcome Results as reported in Systematic review
Level of Level of population the systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
effect.”
Linde and Chapman et al Women aged Individual Placebo Number of patients Similar response in both Not reported
Melchart (1994) between 18-45 simillimum given in assessed globally as groups. Significance of
(1998) [Level II] years with 3 doses at 12 hour improved inter-group differences
d premenstrual intervals, repeated not reported
[Level I] Jadad score 4
AMSTAR: 8/11 N=10 syndrome or new remedy at Intervention group: 2/5
follow-up (40%)
Control group: 3/5 (60%)
SR of
homeopathy Yakir et al (1994) Women with Individual Placebo Number of patients Greater improvement in
for multiple [Level II] premenstrual simillimum assessed globally as homeopathy group.
conditions Quality not syndrome improved Significance of inter-
specified group differences not
N=23 reported
Intervention group: 75%
Control group: 25%
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; C, centesimal; CAM, complementary and alternative medicines; MDQ, Menstrual Distress Questionnaire; PAF,
Premenstrual Assessment Form; SR, systematic review.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
d
The Jadad scale assesses the quality of published clinical trials based methods relevant to random assignment, double blinding and the flow of patients. The range of possible scores is zero
(bad quality) to 5 (good quality).
Evidence statement
One systematic review of medium quality identified one small randomised controlled trial (quality
not reported; 71 participants) that compared homeopathy with placebo for suppression of lactation
in postpartum women who had elected not to breastfeed. LOC: Very low.
Based on only one small study of unknown quality there is no reliable evidence on which to draw a
conclusion about the effectiveness of homeopathy compared to placebo for the suppression of
lactation in postpartum women who elect not to breastfeed.
Table 53 Evidence summary table: the effectiveness of homeopathy for suppressing lactation in postpartum women who elect not to breastfeed
Study ID Included study Patient Intervention Comparator Outcome Results as reported in Systematic review
Level of Level of population the systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Oladapo and Berrebi et al Postpartum Five homeopathic pills Placebo. All Milk secretion (VAS) “Berrebi 2001 (71 women) “This review did not show
Fawole (2012) (2001) women who twice daily for 10 days. patients received suggested a lower risk of sufficient evidence to
[Level I] [Level II] elected not All patients received an an anti- Breast engorgement treatment failure when indicate if other
AMSTAR: 8/10 Quality not to anti-inflammatory inflammatory (VAS) homeopathic preparation pharmacologic agents
specified breastfeed treatment (naproxine- treatment (with anti-inflammatory (includes homeopathic
SR of CAM for the N=71 Apranax) for 5 days. (naproxine- Breast pain (VAS) and analgesic properties) preparation) are useful in
suppression of Apranax) for 5 was compared with suppressing the symptoms of
lactation days placebo on days two and lactation postpartum, as they
four postpartum.” are all based on individual
small trials.”
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; CAM, complementary and alternative medicines; SR, systematic review; VAS, visual analogue scale.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
Evidence statement
One systematic review of medium quality identified two randomised controlled trials (medium to
good quality; 40 and 97 participants) that compared homeopathy with placebo for the treatment of
children with adenoid vegetation. LOC: Low.
Based on the body of evidence evaluated in this review homeopathy is not more effective than
placebo for the treatment of children with adenoid vegetation.
Table 54 Evidence summary table: the effectiveness of homeopathy for the treatment of adenoid vegetation
Study ID Included Patient Intervention Comparator Outcome Results as reported in Systematic
Level of study population the systematic review review
a
evidence Level of interpretation
b a
Quality evidence
c
Quality
Sample size
Altunc et al Furuta et al Patients with Standardised and individualised Placebo Size of adenoid No significant difference “Homeopathic
(2007) (2003) adenoid homeopathy, material potencies, 4 months, vegetation treatments were
[Level I] [Level II] vegetation; treatment regimen not reported not effective for
d Symptom No significant difference
AMSTAR: 6/10 Jadad score 4 Intervention Agraphis nutans 6C potency reducing the size
group and questionnaire of adenoid
N=40 Thuya 6C potency
SR of control group: Adenoid 21C potency in addition to Adverse events No adverse events vegetations and
homeopathy 3-7 years old; individualised remedies preventing the
for multiple 57% male need for
conditions adenoidectomy.”
Feuchter et al Patients with Standardised homeopathy, material Placebo Need for No significant difference
(2001) adenoid potencies, 3 months adenoidectomy
[Level II] vegetation; Nux vomica D200 potency, 5 globules after 3 months
d Intervention of treatment
Jadad score 5 once at the start of the study
N=97 and control Okoubaka D3 potency, 15 globules daily
group: mean Adverse events Main adverse events:
before meals from the first day for 4 acute inflammation of the
age 6 years; weeks
65% male middle ear (5
Tuberculinum D200 potency, 5 globules homeopathy, 6 placebo),
once 4 weeks after the start of the study influenza (4 in both
Concomitant Barium iodatum D4 potency, 3 tablets groups), acute tonsillitis (3
treatment: daily before meals from weeks 4-8 homeopathy, 5 placebo),
acute
Barium iodatum, D6 potency, 3 tablets cough (5 homeopathy),
intercurrent
daily for 4 weeks from weeks 8-12 scarlet fever (2 in both
diseases were
groups), rhinitis (2 in both
treated
groups), digestive
homeopathically
complaints (1 in both
if possible so as
groups)
not to
compromise the
effect of
homeopathic
remedies
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; C, centesimal; D, decimal; NR, not reported; SR, systematic review.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
d
The Jadad scale assesses the quality of published clinical trials based methods relevant to random assignment, double blinding and the flow of patients. The range of possible scores is zero
(bad quality) to 5 (good quality).
Table 55 Matrix indicating the studies that were included in the systematic reviews of allergic rhinitis
Systematic review
Ernst (2011) Passalacqua Cucherat et Linde et al Bellavite et
[Level I] et al (2006) al (2000) (1997) al (2011)
[Level I] [Level I] [Level I] [Level I/III]
Kim et al (2005)
[Level II]
Aabel (2001)
[Level II]
Aabel et al (2000)
[Level II]
Aabel (2000)
[Level II]
Taylor et al (2000)
[Level II]
Weiser et al (1999)
[Level II]
Wiesenauer et al (1990)
Study ID
[Level II]
Reilly et al (1986)
[Level II]
Hardy (1984)
[Level II]
Wiesenauer et al (1983)
[Level II]
Witt et al (2005)
[Level III-2]
Micciche et al (1998)
[Level III-2]
The systematic review by Bellavite et al (2011) (AMSTAR score 5/10) aimed to evaluate the
effectiveness of homeopathy for the treatment of a range of conditions including respiratory
allergies. The review included the majority of the Level II and III-2 trials (11 Level II studies and two
Level III-2 studies). The method used to assess the quality of the included studies was unclear,
although the relatively poor quality was alluded to throughout the review. The authors suggested
that the “major quality problems in most trials” were the limited details provided about allocation
concealment methods, imprecise outcomes, and the poor reporting of dropouts and withdrawals.
Bellavite et al (2011) stated that any meta-analysis was precluded due to the poor quality of many
trials and the high level of heterogeneity. Instead, the systematic review authors offered a “semi-
quantitative” evaluation when multiple studies on the same homeopathic approach and indication
were available. They concluded that, for the treatment of allergic rhinitis, there was “strong positive
evidence” for the effectiveness of homeopathic Galphimia glauca; “good positive evidence” for the
effectiveness of individualised homeopathy; and “unclear or conflicting evidence” for the
effectiveness of homeopathic immunotherapy.
Passalacqua et al (2006) (AMSTAR score 4/10) performed a broad systematic review of
complementary and alternative medicines that are commonly used in patients with rhinitis and
asthma. The review included seven Level II studies that examined various homeopathic interventions
in patients with seasonal or perennial allergic rhinitis. Of the seven studies, six were given Jadad
scores of 5 (Aabel, 2000; Aabel et al, 2000; Kim et al, 2005; Reilly et al, 1986; Taylor et al, 2000;
Weiser et al, 1999) and one received a Jadad score of 4 (Wiesenauer and Gaus, 1985). The
overwhelming majority of outcomes across the trials found no significant difference between the
homeopathic interventions and placebo.
Passalacqua et al (2006) reported the results of the individual studies in a way that was difficult to
interpret. For example, the results of Reilly et al (1986) were reported as a “decrease in symptom
score, visual analog scale, and use of antihistamines”; however, it was not clear whether the
decrease referred to a decrease within the homeopathy group compared to baseline, or a decrease
relative to placebo. Overall, Passalacqua et al (2006) concluded that the few positive results
described in allergic rhinitis in good-quality trials were counterbalanced by an equal number of
negative trials.
Linde et al (1997) (AMSTAR score 9/11) conducted a systematic review and meta-analysis that aimed
to “assess whether the effect seen with homeopathic remedies is equivalent to that seen with
placebo”. Linde et al (1997) identified six Level II studies that examined the effects of homeopathic
treatments on patients with allergic rhinitis. Three studies received a Jadad score of 3 (Reilly and
Taylor, 1985; Wiesenauer et al, 1990; Wiesenauer and Ludtke, 1995), two studies received Jadad
scores of 4 (Wiesenauer et al, 1983; Wiesenauer and Gaus, 1985), and one study received a Jadad
score of 5 (Reilly et al, 1986) (see Table 56). Linde et al (1997) noted that all of the trials that
examined allergic rhinitis had a high number of dropouts and withdrawals.
In contrast to the approach taken by Bellavite et al (2011), Linde et al (1997) undertook a meta-
analysis of the latter four Level II studies (by Wiesenauer and others) that examined homeopathic
Galphimia glauca in patients with allergic rhinitis. The raw data from continuous outcomes were
used to calculate odds ratios by the authors of the systematic review. The odds ratios of all of the
four individual studies favoured homeopathy, and in two of the four studies the result was
statistically significant. After the results were pooled, the odds ratio of 1.87 (95% CI 1.37, 2.56)
suggested that Galphimia glauca is significantly more effective than placebo in the treatment of
allergic rhinitis. Nevertheless, the overall conclusion of the systematic review by Linde et al (1997)
was that there is “insufficient evidence from these studies that homeopathy is clearly efficacious for
any single clinical condition”.
Ernst (2011) (AMSTAR score 5/10) performed a systematic review to assess the efficacy of
homeopathic Galphimia glauca in patients with allergic rhinitis. The review included the same four
Level II studies that were meta-analysed by Linde et al (1997) (Wiesenauer et al, 1983; Wiesenauer
and Gaus, 1985; Wiesenauer et al, 1990; and Wiesenauer and Ludtke, 1995). Ernst (2011) reported
that three of the Level II studies (two with Jadad scores of 4 and one with a Jadad score of 5) found
significant improvements in the primary outcome (a non-validated symptom scale; self-assessed by
the patient and verified by the physician) in favour of Galphimia glauca over placebo. However, one
study (Wiesenauer and Gaus, 1985; Jadad score 5) found no significant inter-group differences. The
conclusion drawn in the systematic review was that there is some evidence to suggest that
Galphimia glauca may be effective for symptomatic treatment of allergic rhinitis; however the
preliminary studies require independent replication.
Finally, Cucherat et al (2000) (AMSTAR score 10/11) aimed to answer the question of “whether there
is any evidence from randomised controlled trials that homeopathy is efficacious for the treatment
of disease in humans”. The systematic review included one Level II study of acute allergic rhinitis
(Reilly et al, 1986). Reilly et al (1986) used a visual analogue scale to compare overall symptom
intensity between allergic rhinitis patients treated with homeopathy or placebo. A significant
difference was reported between the groups that favoured homeopathy (p=0.018). The quality of the
study was not reported by Cucherat et al (2000), although a comment was made that overall the
studies of high methodological quality were more likely to have negative results in terms of the
efficacy of homeopathy, compared to low quality studies. Cucherat et al (2000) concluded that there
is insufficient evidence to conclude that homeopathy is clinically effective for any condition examined
in their review, which included allergic rhinitis.
Reviewer comments
Poor reporting of the individual study results was a major limitation of the systematic reviews,
particularly those conducted by Bellavite et al (2011) and Passalacqua et al (2006). For example, it
was commonly stated that homeopathy was “better than placebo” with no mention of the statistical
significance of the results. It was unclear whether the lack of numerical data stemmed from the
individual Level II studies or the review itself, however if the limitation was with the Level II studies
then this should have been stated to clarify the omission. Similarly, it was difficult to ascertain
whether results such as “significant relief in verum group” were referring to a significant
improvement from baseline or a significant improvement compared to placebo. This made it difficult
for the evidence reviewer to critique the overall conclusions drawn by the systematic review authors.
The evidence reviewer notes that it was often difficult to determine from the systematic reviews
whether the studies examined allergic or non-allergic rhinitis. Where possible, studies that related to
allergic rhinitis (where the systematic review explicitly used the word “allergic”) have been discussed
in Section 4.14.2 and studies that related to non-allergic rhinitis (where none of the systematic
reviews explicitly used to word “allergic”) have been discussed in Section 4.14.7; however, it is
possible that the studies have not always been correctly categorised.
Evidence statement
Five systematic reviews of poor to good quality identified 13 randomised controlled trials
(unreported or medium to good quality; total of 1436 participants, range: 39-243) that compared
homeopathy with placebo for the treatment of people with allergic rhinitis.
Though not the largest study identified in this body of evidence, and while it is below the agreed
threshold for a sufficiently sized study, one good quality study with 144 participants (Reilly et al,
1986) reported a significant difference in favour of homeopathy over placebo. However, the findings
of this study were not confirmed by other good quality, sufficiently sized studies.
Overall, these studies are of insufficient quality and/or size to warrant further consideration of their
findings. LOC: Low.
Based on the body of evidence evaluated in this review there is no reliable evidence that
homeopathy is more effective than placebo for the treatment of people with allergic rhinitis.
Two systematic reviews of poor quality identified one small randomised controlled trial (good
quality; 147 participants) and two prospectively designed, non-randomised controlled studies
(quality not reported; 70 and 178 participants) that compared homeopathy with other therapies
(including anti-histamines, cortisone and intranasal cromolyn sodium) for the treatment of people
with allergic rhinitis.
These studies are of insufficient quality and/or size to warrant further consideration of their findings.
LOC: Low.
Based on the body of evidence evaluated in this review there is no reliable evidence that
homeopathy is as effective as the other therapies for the treatment of people with allergic rhinitis.
Table 56 Evidence summary table: the effectiveness of homeopathy for the treatment of allergic rhinitis
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the systematic Systematic review
Level of Level of population review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Ernst (2011) Wiesenauer and Patients Galphimia Placebo Symptom rating Differences between groups were “Three RCTs reported
[Level I] Ludtke (1995) with glauca-D4; scales (not statistically significant only for ocular significant result in favour of
AMSTAR: 5/10 [Level II] allergic dosage validated; self- symptoms. GG over placebo, while one
d rhinitis individualised; assessed by the study failed to yield significant
Jadad score 4 Improvement by end of treatment in
SR of N=164 duration of 4 patient and intervention group [89% ocular, 80% nasal] inter-group differences. No
homeopathy weeks verified by the and comparator group [63% ocular, 69% serious adverse effects were
for allergic physician) nasal]. reported in any of the trials”.
rhinitis Adverse events No adverse events were reported in
“In conclusion, three of the
intervention group.
four currently available
Wiesenauer et al Patients Galphimia Placebo Symptom rating Statistically significant difference (p=NR) placebo-controlled RCTs of
(1990) with glauca-C2; scales (not Improvement by end of treatment in homeopathic GG suggest this
[Level II] allergic dosage validated; self- intervention group [88% ocular, 76% nasal] therapy is an effective
Jadad score 4
d rhinitis individualised; assessed by the and comparator group [60% ocular, 67% symptomatic treatment for
duration of 33 patient and nasal]. hay fever. There are, however,
N=243
days on average verified by the important caveats. Most
physician) essentially, independent
replication would be required
Wiesenauer and Patients Galphimia 2 groups: Symptom rating No significant difference. before GG can be considered
Gaus (1985) with glauca -D6; Placebo; scales (not Improvement by end of treatment in for the routine treatment of
[Level II] allergic dosage Galphimia validated; self- intervention group [80% ocular, 78% nasal], hay fever.”
d rhinitis individualised; assessed by the
Jadad score 5 glauca diluted diluted homeopathy remedy group [66%
duration of 5 -6 patient and
N=213 by factor of 10 ocular, 51% nasal], placebo group [65%
weeks on verified by the ocular, 58% nasal].
average physician)
Wiesenauer et al Patients Galphimia Placebo Symptom rating Statistically significant difference (p=NR)
(1983) with glauca-D4; scales (not Improvement by end of treatment in
[Level II] allergic dosage validated; self- intervention group [81% (95% CI 65, 92)] and
d rhinitis individualised; assessed by the
Jadad score 5 comparator group [57% (95% CI 39, 74)]
N=121 duration of 39 patient and
verified by the
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the systematic Systematic review
Level of Level of population review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
days on average physician)
Passalacqua et Kim et al (2005) Patients Homeopathic Placebo Three QoL Significant improvement in active group “Some positive results were
al (2006) [Level II] with grass, trees, questionnaires (compared to placebo or baseline?) described in rhinitis in good-
d allergic weeds mix quality trials, but an equal
[Level I] Jadad score 5
AMSTAR: 4/10 N=40 rhinitis number of negative studies
counterbalance the positive
Aabel (2000) Patients Birch 30c Placebo Rhinitis No effect on symptoms ones.”
SR of
[Level II] with symptoms
homeopathy d
Jadad score 5 seasonal “It is not possible to provide
for allegeric
N=80 allergic evidence-based
rhinitis and
rhinitis recommendations for the use
allergic asthma
Aabel et al Patients Birch 30c Placebo Rhinitis No effect on symptoms of homeopathy to treat
(2000) with symptoms allergic rhinitis.”
[Level II] seasonal
d allergic
Jadad score 5
N=70 rhinitis
Weiser et al Patients Nasal Luffa Nasal cromone Rhinitis Homeopathy and nasal cromone are
(1999) with compositum symptoms equivalent
[Level II] seasonal Heel
d allergic
Jadad score 5
N=147 rhinitis
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the systematic Systematic review
Level of Level of population review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Reilly et al Patients 30c dilution grass Placebo Symptom score Decrease (presumably in homeopathy
(1986) with pollen group?). No mention of placebo or between-
[Level II] seasonal group differences
d allergic
Jadad score 5
rhinitis VAS Decrease (presumably in homeopathy
N=144 (reported group?). No mention of placebo or between-
incorrectly in SR group differences
as N=158)
Use of Decrease (presumably in homeopathy
antihistamines group?). No mention of placebo or between-
group differences
Wiesenauer and Patients Galphimia Conventional NR No significant difference between active and
Gaus (1985) with homeopathic dilution/placebo placebo treatments
[Level II] allergic dilution
d oculo-
Jadad score 4
N=164 rhinitis
Cucherat et al Reilly et al Patients Fixed, mixed Placebo VAS of overall Significant difference in favour of “The strength of this evidence
(2000) (1986) with grass pollens symptom homeopathy (p=0.018) is low because of the low
[Level I] [Level II] allergic 30°C intensity methodological quality of the
AMSTAR: Quality not rhinitis trials. Studies of high
e methodological quality were
10/11 specified
N=144 (reported more likely to be negative
SR of incorrectly in SR than the lower quality studies.
homeopathy as N=158) Further high quality studies
for multiple are needed to confirm these
conditions results.”
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the systematic Systematic review
Level of Level of population review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
all clinical conditions and is
not specific to allergic rhinitis)
f
Linde et al Reilly et al Patients Pollen C30 Placebo VAS Odds ratio favoured homeopathy The pooled fixed effects and
(1997) (1986) with improvement pooled random effects of four
[Level I] [Level II] allergic (mm) Level II studies of Galphimia
AMSTAR: 9/11 Quality score rhinitis glauca for pollinosis found an
g odds ratio of 1.87 (95% CI
100/93
SR of N=144 (reported 1.37, 2.56) at 4 weeks (as per
homeopathy incorrectly in SR Erratum in Linde, 1998)
for multiple as N=162)
conditions f
“The results of our meta-
Reilly and Taylor Patients Pollen C30 Placebo Global Odds ratio favoured homeopathy analysis are not compatible
(1985) with assessment with the hypothesis that the
[Level II] allergic patient clinical effects of homeopathy
Quality score rhinitis are completely due to
g
60/50 placebo. However, we found
N=39 insufficient evidence from
f these studies that
Wiesenauer and Patients Galphimia D4 Placebo Improvement Odds ratio favoured homeopathy. homeopathy is clearly
Ludtke (1995) with ocular Intervention (responder/ efficacious for any single
[Level II] allergic symptoms randomised): 50/82 clinical condition.”
Quality score rhinitis Control (responder/ randomised): 36/82
g
60/79 Odds ratio (95% CI): 2.00 (1.07, 3.72)
N=164
f
Wiesenauer et al Patients Galphimia C2 Placebo Improvement Odds ratio favoured homeopathy.
(1990) with ocular Intervention (responder/ randomised):
[Level II] allergic symptoms 75/121
Quality score rhinitis Control (responder/ randomised): 52/122
g
60/86 Odds ratio (95% CI): 2.19 (1.31, 3.67)
N=243
f
Wiesenauer and Patients Galphimia D6 Placebo Improvement Odds ratio showed no difference between
Gaus (1985) with ocular homeopathy and placebo.
[Level II] allergic symptoms Intervention (responder/ randomised):
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the systematic Systematic review
Level of Level of population review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Quality score rhinitis 28/71
g
80/79 Control (responder/ randomised): 24/71
N=142 Odds ratio (95% CI): 1.28 (0.64, 2.53)
f
Wiesenauer et al Patients Galphimia D4 Placebo Improvement Odds ratio favoured homeopathy.
(1983) with ocular Intervention (responder/ randomised):
[Level II] allergic symptoms 30/61
Quality score rhinitis Control (responder/ randomised): 20/60
g
80/79 Odds ratio (95% CI): 1.94 (0.93, 4.04)
N=121
Bellavite et al Kim et al (2005) Patients H.I.T. prepared Placebo Symptoms, Better clinical changes in homeopathy group The results of the included
(2011) [Level II] with from individual quality-of-life as compared with placebo studies were combined and
[Level I/III] Quality not allergic allergen questionnaires classified into one of the
AMSTAR: 5/10 specified rhinitis following levels of evidence by
N=40 the systematic reviewers:
SR of Strong positive evidence
Good positive evidence
homeopathy
Unclear or conflicting evidence
for multiple
Aabel (2001) Patients Homeopathic Placebo Symptoms Similar improvement in homeopathy and Negative scientific evidence
conditions
[Level II] with birch pollen (VAS) placebo The evidence for the
Quality not allergic Betula 30c effectiveness of homeopathy
specified rhinitis for the treatment of
N=51 respiratory allergies was
categorised by Bellavite et al
(2011) as follows:
h
Aabel (2000) Children Homeopathic Placebo Symptoms Homeopathy significantly worse than Strong positive evidence :
[Level II] with birch pollen (VAS) placebo Galphimia glauca (low
Quality not allergic Betula 30c homeopathic dilutions) in
specified rhinitis allergic oculorhinitis
N=73
i
Good positive evidence :
Individualised homeopathy in
allergic rhinitis
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the systematic Systematic review
Level of Level of population review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Aabel et al Patients Homeopathic Placebo Symptoms Slightly less symptoms during 10 days;
(2000) with birch pollen scores aggravation after taking homeopathy Unclear or conflicting
j
[Level II] allergic Betula 30c evidence :
Quality not rhinitis Homeopathic immunotherapy
specified of allergic rhinitis
N=66
Taylor et al Patients Individual Placebo (H.I.T.) Symptoms Slightly better outcomes in homeopathy
(2000) with allergen (VAS) and nasal group
[Level II] allergic air flux tests
Quality not rhinitis
specified
N=50
Weiser et al Patients Low dilution Standard Symptoms and Equivalence of homeopathy and
(1999) with homeopathic intranasal quality-of-life conventional therapy
[Level II] allergic complex therapy based questionnaire
Quality not rhinitis formulation on cromolyn
specified Luffa sodium
N=146 compositum
Wiesenauer and Patients Galphima 4x Placebo Eye and nose Significant relief in homeopathy group
Ludtke (1995) with symptoms
[Level II] allergic
Quality not oculo-
specified rhinitis
N=115
Wiesenauer and Patients Galphimia 2c Placebo Eye and nose Significantly less eye symptoms in
Ludtke (1987) with symptoms homeopathy group
[Level II] allergic
Quality not oculo-
specified rhinitis
N=132
Reilly et al Patients Pollens 30c Placebo Symptoms H.I.T. better than placebo
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the systematic Systematic review
Level of Level of population review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
(1986) with (H.I.T.) (VAS)
[Level II] allergic
Quality not oculo-
specified rhinitis
N=144
Wiesenauer and Patients Galphimia Placebo (e Eye and nose Trend to better improvement in the
Gaus (1985) with glauca 6x Galphimia symptoms homeopathic group; not statistically
[Level II] allergic dynamised glauca 6x non- significant; less symptoms in patients taking
Quality not oculo- dynamised) dynamised homeopathic medicine than
specified rhinitis other groups
N=164
Hardy (1984) Patients Homeopathic Placebo Symptoms H.I.T. better than placebo
[Level II] with immunotherapy
Quality not allergic (H.I.T.) made
specified oculo- with house dust
N=70 rhinitis potencies
(house
dust)
Witt et al (2005) Patients Classic Conventional Symptoms, Better outcomes in homeopathic group
[Level III-2] with homeopathy care quality-of-life
Quality not allergic questionnaires,
specified diseases costs
N=178 including
rhinitis
and
asthma
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the systematic Systematic review
Level of Level of population review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
specified rhinitis treatment)
N=70
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; C, centesimal; CI, confidence interval; D, decimal; GG, Galphimia glauca; H.I.T, homeopathic immunotherapy; NR, not
reported; SR, systematic review; VAS, visual analogue scale.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
d
The Jadad scale assesses the quality of published clinical trials based methods relevant to random assignment, double blinding and the flow of patients. The range of possible scores is zero
(bad quality) to 5 (good quality).
e
Quality of included studies was not formally assessed by the authors. The authors noted that “the only criterion for quality used for selection was adequate concealment of treatment
allocation (by a suitable randomisation method)”.
f
Odds ratios were calculated by the systematic reviews based on raw data provided in Level II studies.
g
Jadad score / IV score, where the scores are expressed as a percentage of the maxium possible score. Note: the maximum possible Jadad score is 5; the maximum possible internal validity
h
score is 7. Significant evidence of a clear benefit from >2 properly randomised trials, or from one properly conducted meta-analysis on homogenous trials.
i
Statistically significant evidence of a benefit from 1-2 properly randomised trials, or evidence of benefit from at least 1 randomised trial plus >1 observational cohort/case-control/non-
randomised trial.
j
Conflicting evidence from multiple trials or observational studies without a clear majority of the properly conducted trials finding evidence of benefit or ineffectiveness.
4.14.3 Asthma
The effectiveness of homeopathy for the treatment of asthma (including allergic and non-allergic
asthma) was assessed in six systematic reviews (Altunc et al, 2007; Bellavite et al, 2011; Cucherat et
al, 2000; Linde and Melchart, 1998; McCarney et al, 2008; Passalacqua et al, 2006) as summarised in
Table 57 and Table 58. Overall, the six systematic reviews included eight Level II studies (Freitas et al,
1995; Lara-Marquez et al, 1997; Lewith et al, 2002; Matusiewicz, 1995; Matusiewicz et al, 1999; Reilly
et al, 1994; Riveron-Garrote et al, 1998; White et al, 2003).
Table 57 Matrix indicating studies that were included in the systematic review of asthma
Systematic review
Bellavite McCarney Altunc et Passalacqua Cucherat Linde and
et al et al (2008) al (2007) et al (2006) et al Melchart
(2011) [Level I] [Level I] [Level I] (2000) (1998)
[Level I] [Level I] [Level I]
White et al (2003)
[Level II]
Lewith et al
(2002)
[Level II]
Matusiewicz et al
(1999)
[Level II]
Riveron-Garrote
et al (1998)
Study IDs
[Level II]
Lara-Marquez et
al (1997)
[Level II]
Freitas et al
(1995)
[Level II]
Matusiewicz
(1995)
[Level II]
Reilly et al (1994)
[Level II]
McCarney et al (2008) (AMSTAR score 9/11) undertook a Cochrane review of homeopathy for chronic
asthma. McCarney et al (2008) included six studies (see Table 58), comprehensive study details and a
meta-analysis. Four of the Level II studies identified were assessed to be medium to good quality,
including two with a Jadad quality assessment score of 4 (Freitas et al, 1995; Reilly et al, 1994) and
two with a score of 5 (Lewith et al, 2002; White et al, 2003). White et al (2003) compared the efficacy
of individualised homeopathy with placebo in patients with allergic asthma, aged five to 15 years. No
statistically significant differences were found between the treatment arms on any of the reported
outcomes, which included lung function (measured by peak expiratory volume), quality of life,
medication use, global assessment, and days off school. Similarly, the good quality trial by Lewith et
al (2002) examined lung function, medication use and subjective symptoms and found no significant
differences between the homeopathy and placebo groups.
Freitas et al (1995) reported no significant difference between homeopathy (blatta officinalis 6C) and
placebo on any outcome. However, the systematic review authors questioned whether the patient
population of that trial were truly asthmatic (eligible participants were children aged one to 12 years
who had experienced at least three bronchospastic episodes or who had a continuous wheeze for at
least three months). Finally, Reilly et al (1994) examined homeopathy in patients with allergic
asthma, the majority of whom were sensitive to house dust mite. Reilly et al (1994) reported
significant differences in favour of homeopathy based on the severity of symptoms measured on a
visual analogue scale (p=0.003) and also between the medians of the groups based on forced vital
capacity (p=0.03).
In addition to the studies outlined above, McCarney et al (2008) also identified two low quality
studies that examined the efficacy of homeopathy in patients with bronchial asthma. Matusiewicz et
al (1995) and Matusiewicz (1999) received Jadad scores of 1 and 2, respectively. In addition to
significant methodological flaws, the methods and results were difficult to interpret in both studies
due to poor reporting. Matusiewicz et al (1999) reported a “significant effect” for immune
functioning, global ratings and number of infections; however no p-values were reported and it was
unclear whether the “significant effect” referred to inter-group differences or differences in the
homeopathy arm from baseline to follow-up. Matusiewicz et al (1995) reported a significant benefit
in the homeopathy group based on peak expiratory flow; however, no p-value was provided to
support the finding. In addition, the authors of that study reported a “clear difference” in forced
expiratory volume, forced vital capacity and steroid use in favour of the homeopathy group; although
no p-values or standard deviations were reported.
Overall, the ability to pool the results of the six included studies was limited due to disparate
reporting of outcomes. The only outcome for which pooled effect sizes were estimable was forced
expiratory volume in adults. McCarney et al (2008) pooled the results from Lewith et al (2002),
Matusiewicz et al (1999) and Matusiewicz et al (1995) and no significant difference was observed
between treatment groups, based on a total of 366 participants (effect size: -0.06 litres; 95% CI -0.17,
0.04; p=0.24), see Table 59. McCarney et al (2008) concluded that there is “not enough evidence to
reliably assess” the efficacy of homeopathy in asthma. The authors highlighted the fact that the
results regarding lung function were mixed and that no trials included in their systematic review
found a significant difference between homeopathy and placebo on a validated symptom scale.
Finally, McCarney et al (2008) stated that although there is no plausible scientific rationale behind
homeopathy, there may be “non-specific benefits associated with a ‘holistic’ package of care”.
Altunc et al (2007) (AMSTAR score 6/10) performed a systematic review to assess the efficacy of
homeopathy in various conditions that commonly affect children and adolescents, including asthma.
Two of the Level II studies discussed above (Freitas et al, 2005; White et al, 2003) were identified that
compared the efficacy of homeopathy to placebo. One of the studies (Freitas et al, 2005; Jaded score
4) adopted a formulaic approach in which all patients received homeopathic blatta orentalis (6C
potency) for six months, and found no significant difference between the homeopathic remedy and
placebo in terms of intensity, frequency and duration of asthma attacks. Patients recruited into the
study by White et al (2003) (Jadad score 5) received individualised homeopathy for one year, and
reported no significant difference between the homeopathy and placebo groups on the “active
quality of living” subscale on the Childhood Asthma Questionnaire.
The Level II study by White et al (2003) was also included in the systematic review by Passalacqua et
al (2006) (AMSTAR score 4/10). The review examined the efficacy of homeopathy for the treatment
of asthma and rhinitis. Passalacqua et al (2006) reported that White et al (2003) found no significant
differences between homeopathy and placebo on any of the four outcomes presented (asthma-
related quality of life, peak expiratory flow, use of β2-agonists, and missing days). The Level II studies
by Lewith et al (2002) and Reilly et al (1994) examined asthma-related outcomes (forced expiratory
volume, peak expiratory flow, asthma symptoms and use of other asthma medications) in patients
with allergic asthma. The only significant inter-group difference on any outcome was a significant
improvement of asthma symptoms according to a visual analogue scale (Reilly et al, 1994), although
the p-value was not reported. Passalacqua et al (2006) concluded that “three well-conducted trials
showed no or marginal effects in asthmatic patients”.
In addition to most of the aforementioned studies (namely Lewith et al, 2002; Matusiewicz, 1995;
Matusiewicz et al, 1999; Reilly et al, 1994; White et al, 2003), Bellavite et al (2011) (AMSTAR score
5/10) also included a further two Level II studies (Lara-Marquez et al, 1997; Riveron-Garrote et al,
1998) in their systematic review. The review aimed to evaluate the effectiveness of homeopathy for
the treatment of upper airways and ear-nose-throat ailments, respiratory allergies, arthrorheumatic
diseases and osteoarthritis. According to Bellavite et al (2011), Riveron-Garrote et al (1998) reported
a higher reduction of asthma attacks in the homeopathy group compared to placebo; however it was
not clear from the systematic review whether this reduction was clinically or statistically significant.
Similarly, it was reported that Lara-Marquez et al (1997) found “significant changes” in laboratory
markers in favour of homeopathy; however, the clinical and statistical significance was also not clear
and there were only 19 participants in the study.
Linde and Melchart (1998) (AMSTAR score 8/11) conducted a systematic review that examined the
efficacy of individualised homeopathy across a number of clinical conditions. They also identified the
study of homeopathy for the treatment of allergic asthma by Lara-Marquez et al (1997) which,
according to Linde and Melchart (1998), was available as an abstract only. Based on the limited
information available, Linde and Melchart (1998) reported that homeopathy was “better than
placebo”; however, the outcome used to measure treatment superiority and the magnitude of the
difference between treatment groups was not clear.
Cucherat et al (2000) (AMSTAR score 10/11) conducted a broad review that aimed to answer the
question of “whether there is any evidence from randomised controlled trials that homeopathy is
efficacious for the treatment of disease in humans”. Cucherat et al (2000) included one Level II study
in their review (Reilly et al, 1994), which showed a significant difference in favour of homeopathy
based on the severity of symptoms measured on a visual analogue scale (p=0.003). The authors
provided an overall, generalised conclusion that “it is clear that the strength of available evidence is
insufficient to conclude that homeopathy is clinically effective”.
Reviewer comments
McCarney et al (2008) provided a detailed discussion of the major limitations of the included studies.
Importantly, homeopathy was assessed in addition to conventional medications (in some cases for
ethical reasons), making it hard to determine whether homeopathy itself provides any benefit.
In addition, the interventions varied substantially between the included trials and the evidence
reviewer thought that some of the studies examined interventions that were not representative of
normal homeopathic treatment strategies. For example, Lewith et al (2002) and Reilly et al (1994)
used “one off” treatments, while in White et al (2003) patients were involved in six consultations,
extensive telephone contact and as many remedy changes as were deemed appropriate.
The evidence reviewer also notes that it was often difficult to determine from the systematic reviews
whether the studies examined allergic or non-allergic asthma. As such, only one ‘asthma’ section has
been included in the Overview Report which includes studies that probably examine both allergic and
non-allergic asthma.
Evidence statement
Six systematic reviews of poor to good quality identified eight randomised controlled trials (poor to
good quality; total of 675 participants, range: 19-242) that compared homeopathy with placebo for
the treatment of people with asthma.
The one medium-sized, good-quality trial (242 participants) did not detect a difference between
homeopathy and placebo in the treatment of people with asthma. LOC: Low - moderate.
Based on the body of evidence evaluated in this review homeopathy is not more effective than
placebo for the treatment of people with asthma.
Table 58 Evidence summary table: the effectiveness of homeopathy for the treatment of asthma
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Bellavite et White et al Children with Individualised Placebo Quality-of-life No changes in quality of life, The results of the included
al (2011) (2003) allergic homeopathy questionnaires, small not significant studies were combined and
[Level I] [Level II] asthma (mild symptoms and tests improvement of symptoms in classified into one of the
AMSTAR: Quality not to moderate) homeopathy group following levels of evidence by
5/10 specified the systematic reviewers:
N=96 Strong positive evidence
Good positive evidence
SR of
Lewith et al Allergic Allergen (dust mite) Placebo H.I.T. Symptoms (VAS) No final therapeutic effect, initial Unclear or conflicting evidence
homeopathy
(2002) asthma 30c and expiration flux aggravation Negative scientific evidence
for multiple
[Level II] (FEV) The evidence for the
conditions
Quality not effectiveness of homeopathy for
specified the treatment of respiratory
N=242 allergies was categorised by
Bellavite et al (2011) as follows:
Matusiewicz et al Patients with Homeopathic complex Placebo Use of unspecified Slight decrease of conventional
(1999) allergic Asthma H Inj. ‘standard‘ drugs, medication and infections; no Good positive evidence :
d
[Level II] asthma Plfugerplex, laboratory and change in spirometric tests Individualised homeopathy in
Quality not subcutaneously spirometric tests asthma
specified
N=84 Unclear or conflicting evidence :
e
Riveron-Garrote Patients with Individualised Placebo General symptoms Higher reduction of asthma Homeopathic immunotherapy of
et al (1998) allergic homeopathy and attack intensity attacks in homeopathy group asthma
[Level II] asthma
Quality not
specified
N=80
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
specified markers
N=19
Matusiewicz Patients with Homeopathic complex Placebo Respiratory tests Clinical improvement only in
(1995) allergic Engystol-N homeopathy group
[Level II] asthma
Quality not
specified
N=40
Reilly et al (1994) Patients with Unspecified ‘standard‘ Unspecified Symptoms (VAS) Less symptoms in the
[Level II] allergic drugs + allergen 30C ‘standard‘ and respiratory homeopathy group than placebo,
Quality not asthma (H.I.T.) drugs + tests no differences in tests
specified placebo
N=28
McCarney et White et al Children with Any number of Placebo Days off school No statistically significant “There is not enough evidence to
al (2008) (2003) allergic individualised (measured as a differences between the reliably assess the possible role
[Level I] [Level II] asthma homeopathy change from the treatment groups of homeopathy in asthma. As
f diagnosed by
AMSTAR: Jadad score 5 prescriptions previous month; well as randomised trials, there
GP and
9/11 N=93 prescription
increased, no is a need for observational data
for either change, or reduced) to document the different
SR of beta-agonist methods of homeopathic
or
PEF No significant difference prescribing and how patients
homeopathy between treatment groups in
for asthma
corticosteroid respond. This will help to
inhaler in terms of improvement establish to what extent people
previous 3 respond to a ‘package of care’
months Asthma-related QoL No significant difference
between treatment and control rather than the homeopathic
aged 5-15
intervention alone”.
years
Use of β2-agonists No significant difference in terms
of use of inhaler
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Global assessment No significant difference “The currently available evidence
of change between treatment groups is insufficient to assess reliably
the possible role of homeopathy
Adverse events No significant intergroup in the treatment of asthma.
differences reported Whilst the scientific rationale
behind homeopathy remains
unproven, non-specific benefits
associated with a ‘holistic’
package of care may exist”.
Lewith et al Patients with Isopathy (30C house Placebo Lung function No significant difference
(2002) mild to severe dust mite), 3 doses
allergic orally in 24 hours Use of β2-agonists No significant difference in
[Level II]
f asthma bronchodilator usage after
Jadad score 5
positive skin
treatment of at 15 week follow- “The effect of homeopathy on
N=242 up
prick test to asthma has yet to be proven in a
house dust randomised study. However, the
mite with
Subjective No adverse events reported
varied quality of the studies
response symptoms
precludes us from extrapolating
greater than any effects observed to the
aeroallergens
general population level”.
tested
Matusiewicz et al Patients with 1 ampoule of Asthma Placebo Immune “Significant effect” reported – “No trials reported a significant
(1999) chronic H (a complex remedy functioning unclear whether this was difference on validated
[Level II] bronchial consisting of 14 between treatment groups of symptoms scales. There were
f asthma homeopathic from baseline to follow-up
Jadad score 2 conflicting results in terms of
N=84 diagnosis potencies of D3, D4, lung function between the
based on D5 and Global ratings “Significant effect” reported –
studies”
history, unclear whether this was
D6) injected
spirometry, between treatment groups of
subcutaneously at “There has been only a limited
physical from baseline to follow-up
examination
intervals of 5 to 7 days attempt to measure a ‘package
and Number of “Significant effect” reported – of care’ effect (i.e. the effect of
medication infections unclear whether this was the medication as well as the
use between treatment groups of consultation, which is considered
Triamcinolone from baseline to follow-up a vital part of individualised
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
use for last 5 FVC No significant differences (2.7 homeopathic practice)”
years litres, SD: 0.91 in treatment
group; 2.74 litres, SD: 0.7 in the See Table 59 for results of the
control group) meta-analysis.
Freitas et al Patients with Blatta officinalis C6, 2 Placebo Intensity of asthma No significant difference
(1995) at least 3 globules 3 times per attack between treatment groups
[Level II] bronchospasti day for 6 months
f c episodes Frequency of No significant difference
Jadad score 4
with intervals asthma attack between treatment groups
N=69
of 3 months Duration of asthma No significant difference
or less, or attack between treatment groups
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
continuous
wheeze for at
least 3
g
months
aged 1-12
years
approx. 50%
males and
females
Matusiewicz Patients with 1 ampoule Engystol N Placebo FEV There was a “clear difference”
(1995) corticosteroid (a complex remedy between treatment and control.
[Level II] -dependent consisting of the FEV litres improved from 1.7 at
f bronchial homeopathic baseline to 2.4 after treatment in
Jadad score 1
N=40 asthma remedies Vincetoxin the homeopathy group; placebo
diagnosis D6/D10/ group changed from 1.9 to 1.8
confirmed by D30, Sulfur D4/D10) litres, no SDs reported.
history and injected
spirometry subcutaneously at
intervals of 5 to 7
Patients days.
received FVC There was a “clear difference”
methylxanthi between treatment and control
nes for (treatment group: +1.3 litres
mucolysis and versus control group: 0 litres); no
tetracycline in p-values reported
case of Medication use There was a “clear difference”
exacerbations between treatment and control
in terms of oral steroid use (3 mg
per day in the treatment group
versus 7 mg in the control
group). No SD or p-values
reported
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Reilly et al (1994) Patients with Homeopathic Placebo Severity symptoms Highly significant difference
[Level II] allergic preparation of the quantified by a 100 between treatment groups
f asthma individual allergens in mm VAS (p=0.003). Improvement of
Jadad score 4
N=28 most with potency C30 (30 7.2mm (SD: 10.6mm) in the
sensitivity to dilution steps 1:100) treatment group; deterioration
house- prepared in a water- by 7.8mm (SD: 10.8mm) in the
dustmite alcohol solution and placebo group.
age > 16 years
impregnated on
lactose/sucrose PEF No significant difference
globules (placebo between groups
impregnated with
diluent only). FVC Significant difference between
Treatment consisted the medians of the groups (0.36
of 3 doses of globules litres; 95% CI 0.03, 0.73; p-value
within 24 hours 0.03)
(once).
Altunc et al White et al Children with Individualised Placebo Active quality of No significant difference “Both RCTs reported no
(2007) (2003) allergic homeopathy, potency living subscale of differences compared with
[Level I] [Level II] asthma not reported, 1 year CAQ placebo on several outcome
AMSTAR: Jadad score 5
f 5-15 years old Various remedies in measures, including the
54% male Adverse events Main adverse events include intensity, frequency and duration
6/10 N=93 different potencies
Concomitant exacerbation of eczema (4H, 2P0 of asthma attacks”.
(no details reported).
treatment: β- and asthma (3 both), headache
SR of Adrenergic (3H), fever (1H), sickness (1H),
homeopathy inhalers (all
“The evidence from rigorous
rash (1P), depression and
for multiple patients), clinical trials of any type of
irritability (3P), sleeping
conditions inhaled therapeutic or preventive
difficulties (2P); 1 patients was
steroids (33H; intervention testing homeopathy
withdrawn because of adverse
36P), sodium for childhood and adolescence
cromoglycate events (cough, behaviour and
ailments is not convincing
(6H; 2P), sleeping disorders)
enough for recommendations in
salbutamol
any condition”.
nebules (1H)
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
(1995) asthma homeopathy, material attack
[Level II] 1-12 years old potencies, 6 months.
f
51% male Frequency of No significant difference
Jadad score 4 Blatta orientalis 6C
Concomitant asthma attack
N=86 potency, two globules
treatment: delivered 3 times
conventional Duration of asthma No significant difference
daily. attack
asthma
medicines (for
prevention or
crisis).
Passalacqua White et al Children with Individual Placebo plus Asthma-related QoL No difference between active Three well-conducted trials
et al (2006) (2003) allergic homeopathy plus drugs group and placebo found no or marginal effects in
[Level I] [Level II] asthma drugs asthmatic patients
f PEF No difference between active
AMSTAR: Jadad score 5
group and placebo
4/10 N=93
Use of β2-agonists No difference between active
SR of group and placebo
homeopathy
for rhinitis Days off school No difference between active
and asthma (measured as a group and placebo
change from the
previous month;
increased, no
change, or reduced)
Lewith et al Patients with Dust mite Placebo FEV No difference between active
(2002) allergic homeopathy group and placebo
[Level II] asthma
f PEF No difference between active
Jadad score 5
group and placebo
N=242
Asthma symptoms No difference between active
group and placebo
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
group and placebo
Reilly et al (1994) Patients with 30c dilution of Placebo Severity symptoms Significant improvement (no p-
[Level II] allergic allergens quantified by a 100 value)
f asthma mm VAS
Jadad score 4
N=28 PEF No change
Histamine No change
challenge
Cucherat et Reilly et al (1994) Patients with Individualised Placebo VAS of overall Significant difference in favour of “The strength of this evidence is
al (2000) [Level II] allergic homeopathic symptom intensity homeopathy (p=0.003) low because of the low
[Level I] Quality not asthma immunotherapy methodological quality of the
h trials. Studies of high
AMSTAR: specified
10/11 N=28 methodological quality were
more likely to be negative than
SR of the lower quality studies. Further
homeopathy high quality studies are needed
for multiple to confirm these results.”
conditions
“It is clear that the strength of
available evidence is insufficient
to conclude that homeopathy is
clinically effective.”
Linde and Lara-Marquez et Patients with Individualised Placebo Unclear “Homeopathy better than No specific conclusions provided
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Melchart al (1997) allergic simillimum placebo” regarding the efficacy of
(1998) [Level II] asthma homeopathy for allergic asthma
[Level I] Quality not were provided.
i
AMSTAR: assessed
8/11 N=19 The study was not included in
the meta-analysis as it was
SR of available as an abstract only.
homeopathy
for multiple
conditions
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; C, centesimal; CAQ, Childhood Asthma Questionnaire; D, decimal; FEV, forced expiratory volume; FVC, forced vital
capacity; NR, not reported; PEF, peak expiratory flow; QoL, quality of life; SD, standard deviation; SR, systematic review; VAS, visual analogue scale.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
d
Statistically significant evidence of a benefit from 1-2 properly randomised trials, or evidence of benefit from at least 1 randomised trial plus >1 observational cohort/case-control/non-
randomised trial.
e
Conflicting evidence from multiple trials or observational studies without a clear majority of the properly conducted trials finding evidence of benefit or ineffectiveness
f
The Jadad scale assesses the quality of published clinical trials based methods relevant to random assignment, double blinding and the flow of patients. The range of possible scores is zero
(bad quality) to 5 (good quality).
g
The authors of the systematic review question whether this is truly asthma.
h
Quality of included studies was not formally assessed by the authors. The authors noted that “the only criterion for quality used for selection was adequate concealment of treatment
allocation (by a suitable randomisation method)”
i
Quality not assessed as the study was available as an abstract only at the time of publication
4.14.4 Bronchitis
The effectiveness of homeopathy for the treatment of patients with bronchitis was assessed in one
systematic review (Cucherat et al, 2000; AMSTAR score 10/11) as summarised in Table 60. Cucherat
et al (2000) (AMSTAR score 10/11) aimed to answer the question of “whether there is any evidence
from randomised controlled trials that homeopathy is efficacious for the treatment of disease in
humans”. The review included one Level II study (Diefenbach, 1997) that had investigated the effect
of the homeopathic treatment, Bronchiselect, in patients with bronchitis. Cucherat et al (2000)
reported that in this Level II study, there was no significant difference in the length of productive
cough between patients in the homeopathy and placebo groups. The quality of Deifenbach (1997)
was not formally assessed; however, a general comment was made in reference to all of the included
studies that “the strength of this evidence is low because of the low methodological quality of the
trials”. Overall, the authors concluded that “it is clear that the strength of available evidence is
insufficient to conclude that homeopathy is clinically effective”.
Evidence statement
One systematic review of good quality identified one medium-sized randomised controlled trial
(quality not reported; 258 participants) that compared homeopathy (Bronchiselect) with placebo for
the treatment of people with bronchitis. LOC: Low.
Based on only one study of unknown quality there is no reliable evidence on which to draw a
conclusion about the effectiveness of homeopathy compared to placebo for the treatment of people
with bronchitis.
Table 60 Evidence summary table: the effectiveness of homeopathy for the treatment of bronchitis
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review interpretation
Level of Level of population systematic review
a a
evidence evidence
b c
Quality Quality
Sample size
Cucherat et al Diefenbach (1997) Patients Bronchiselect Placebo Length of productive No significant difference “It is clear that the strength of
(2000) [Level II] with cough (p=0.86) available evidence is insufficient to
[Level I] Quality not bronchitis conclude that homeopathy is clinically
AMSTAR: 10/11 specified effective”
d
N=258
SR of (Note: this conclusion refers to all
homeopathy clinical conditions and is not specific to
for multiple bronchitis)
conditions
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; SR, systematic review.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
d
209 participants evaluated.
4.14.5 Cough
The effectiveness of homeopathy for the treatment of cough was assessed in one systematic review
(Bellavite et al, 2011) (AMSTAR score 5/10) as summarised in Table 61. The authors conducted a
broad review of homeopathy and immunology across a range of clinical areas. One Level II study was
identified that assessed the efficacy of homeopathy (Drosera) compared to placebo in patients with a
cough (Bordes and Dorfman, 1986). Patients were assessed for symptoms, and it was reported that
67% of patients in the homeopathy group and 27% of patients in the placebo group experienced a
reduction or disappearance of symptoms after one week. However, the significance of the findings
was unknown. The quality of the included study was not formally assessed by Bellavite et al (2011).
Bellavite et al (2011) did not provide any overall conclusion regarding the efficacy of homeopathy for
the treatment of cough in their systematic review.
Evidence statement
One systematic review of poor quality identified one small randomised controlled trial (quality not
reported; 60 participants) that compared homeopathy (Drosera) with placebo for the treatment of
people with a cough. LOC: Very low.
Based on only one small study of unknown quality there is no reliable evidence on which to draw a
conclusion about the effectiveness of homeopathy compared to placebo for the treatment of people
with a cough.
Table 61 Evidence summary table: the effectiveness of homeopathy for the treatment of a cough
Study ID Included study Patient Intervention Comparator Outcome Results as reported in Systematic review
a
Level of Level of evidence population the systematic review interpretation
a c
evidence Quality
b
Quality Sample size
Bellavite et al Bordes and Dorfman Patients with Low-dilution (3C) Placebo Number of patients with Homeopathy group: Bellavite et al (2011) did not
(2011) (1986) a cough homeopathic significant reduction or 20/30 patients (66.67%); provide an overall
[Level I] [Level II] complex in syrup disappearance of Placebo group: 8/30 conclusion for the efficacy of
AMSTAR: 5/10 Quality result not (Drosera) symptoms after one week patients (26.67%). No homeopathy in patients with
reported level of significance a cough.
SR of N=60 reported
homeopathy for
multiple
conditions
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; C, centesimal; SR, systematic review.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
Reviewer comments
The comparator was not specified in the systematic review; however, the evidence reviewer obtained
a copy of the abstract of Mousavi et al (2009), which revealed that the unspecified comparator was
placebo.
Evidence statement
One systematic review of poor quality identified one very small randomised controlled trial (quality
not reported; 30 participants) that compared homeopathy (Ignatia) with placebo for the treatment
of people with oral lichen planus. LOC: Very low.
Based on only one very small study of unknown quality there is no reliable evidence on which to
draw a conclusion about the effectiveness of homeopathy compared to placebo for the treatment of
people with oral lichen planus.
Table 62 Evidence summary table: the effectiveness of homeopathy for the treatment of oral lichen planus
Study ID Included study Patient Intervention Comparator Outcome Results as reported in Systematic review
a
Level of Level of evidence population the systematic review interpretation
a c
evidence Quality
b
Quality Sample size
Bellavite et al Mousavi et al (2009) Patients with Ignatia 30C NR Mean pain score and Significant improvement The authors of the
(2011) [Level II] oral lichen mean lesion size (not in favour of Ignatia after 4 systematic review did not
[Level I] Quality result not planus reported separately) months of treatment; provide a conclusion about
AMSTAR: 5/10 reported p<0.05 the use of Ignatia in patients
N=30 with oral lichen planus
SR of
homeopathy for
multiple
conditions
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; C, centesimal; NR, not reported; SR, systematic review.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
Reviewer comments
The evidence reviewer notes that the results of the four included studies should be interpreted with
caution, as they all used ‘active’ comparators and the authors of the systematic review did not
comment on the appropriateness of the chosen comparators. In particular, the evidence reviewer
questions the use of aspirin for the treatment of rhinitis as there is some evidence that aspirin can
cause or exacerbate rhinitis.
The evidence reviewer also notes that it was often difficult to determine from the systematic reviews
whether the studies examined allergic or non-allergic rhinitis. Where possible, studies that related to
allergic rhinitis (where the systematic review explicitly used the word “allergic”) have been discussed
in Section 4.14.2 and studies that related to non-allergic rhinitis (where none of the systematic
reviews explicitly used to word “allergic”) have been discussed in Section 4.14.7; however, it is
possible that the studies have not always been correctly categorised.
Evidence statement
One systematic review (2011) did not identify any prospectively designed and controlled studies that
assessed the effectiveness of homeopathy compared with placebo for the treatment of people with
non-allergic rhinitis.
One systematic review of poor quality identified two randomised controlled trials (quality not
reported; 53 and 170 participants) and two prospectively designed, non-randomised controlled
studies (quality not reported; 397 and 739 participants) that compared homeopathy with other
therapies (including aspirin and xylometazoline) for the treatment of people with non-allergic
rhinitis.
These studies are of insufficient quality and/or size to warrant further consideration of their findings.
LOC: Low.
Based on the body of evidence evaluated in this review there is no reliable evidence that
homeopathy is as effective as the other therapies for the treatment of people with non-allergic
rhinitis.
Table 63 Evidence summary table: the effectiveness of homeopathy for the treatment of non-allergic rhinitis
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Bellavite et al Maiwald (1988) Patients with Homeopathic Aspirin Symptom Equivalence between homeopathy “Good positive evidence”
(2011) [Level II] acute rhinitis complex Gripp- severity score and aspirin for Euphorbium
[Level I] Quality not heel compositum in rhinitis,
AMSTAR: 5/10 reported based on positive evidence
N=170 from one Level II study and
SR of one Level III-2 study
Gassinger et al Patients with Eupatorium Aspirin Symptom Equivalence between homeopathy
homeopathy
(1981) acute rhinitis perfoliatum 2x severity score and aspirin
for multiple
conditions [Level II]
Quality not
reported
N=53
Schmiedel and Patients with Homeopathic Conventional Patient-reported Significant benefit in homeopathy
Klein (2006) acute rhinitis complex Engystol therapies improvement group (p<0.05)
[Level III-2] (antihistamines, within 3 days Homeopathy group: 77.1%
Quality not antitussives, Conventional treatment group: 61.7%
reported and
General and Homeopathic medicine equivalent
N=397 nonsteroidal
local symptoms to the conventional treatment
anti-
inflammatory
drugs)
Ammerschlager et Patients with Low-dilution Xylometazoline Disease specific Treatments had equivalent
al (2005) rhinitis and homeopathic symptoms efficacy. Clinically relevant
[Level III-2] sinusitis complex reductions observed in both
Quality not formulation groups. Non-inferiority of the
reported Euphorbium homeopathic complex was
N=739 compositum (nasal demonstrated.
spray)
Tolerability Treatments were equivalent.
Good tolerability in both therapies
4.14.8 Sinusitis
The effectiveness of homeopathy for the treatment of patients with rhinosinusitis/chronic sinusitis
was assessed in two systematic reviews (Bellavite et al, 2011; Cucherat et al, 2000) as summarised in
Table 64 and Table 65. In total, the systematic reviews included three Level II studies (Table 64).
Table 64 Matrix indicating the studies that were included in the systematic reviews of sinusitis
Study ID
Zabolotnyi et al (2007) Weiser and Clasen Wiesenauer et al
[Level II] (1994) (1989)
[Level II] [Level II]
Bellavite et al (2011)
Systematic
[Level I]
review
Cucherat et al (2000)
[Level I]
The systematic review by Bellavite et al (2011) (AMSTAR score 5/10) aimed to evaluate the
effectiveness of homeopathy for the treatment of a range of diseases including infections of the
upper airways and ear-nose-throat ailments. Three Level II studies of unspecified quality were
included for the sinusitis indication. Zabolotnyi et al (2007) tested the effect of a homeopathic
complex compared with placebo in patients with maxillary sinusitis. The study found a significant
effect of homeopathy over placebo in the improvement of symptoms. Weiser and Clasen (1994) was
a double-blind, placebo-controlled Level II study that examined the effect of a homeopathic
Euphorbium composition S nasal spray in patients with rhinosinusitis/chronic sinusitis, compared to
placebo. This Level II study also reported a “significantly greater improvement in the homeopathy
group (21.1%) compared to placebo (14.4%)”. The third included Level II study by Wiesenauer et al
(1989) investigated the effect of a low-dilution homeopathic complex in patients with sinusitis. The
study found no effect of homeopathy in a global evaluation and analysis of symptoms. Bellavite et al
(2011) did not formulate a specific conclusion on the effectiveness of homeopathy for the treatment
of sinusitis, but it noted that there was “good positive evidence for Euphorbium compositum in
rhinitis-sinusitis” from the one Level II study (Weiser and Clasen, 1994).
Cucherat et al (2000) (AMSTAR score 10/11) aimed to answer the question of “whether there is any
evidence from randomised controlled trials that homeopathy is efficacious for the treatment of
disease in humans”. The systematic review included one Level II study (Weiser and Clasen, 1994) that
focused on chronic sinusitis. Cucherat et al (2000) stated that there was a significant difference in
cumulative scores in Weiser and Clasen (1994) that favoured homeopathy (p=0.016). The quality of
Weiser and Clasen (1994) was not formally assessed; however, a general comment was made in
reference to all of the included studies that “the strength of this evidence is low because of the low
methodological quality of the trials”. Overall, the authors concluded that “it is clear that the strength
of available evidence is insufficient to conclude that homeopathy is clinically effective”.
Evidence statement
Two systematic reviews of poor and good quality identified three randomised controlled trials
(quality not reported; total of 420 participants, range: 113-155) that compared homeopathy with
placebo for the treatment of people with sinusitis.
These studies are of insufficient quality and/or size to warrant further consideration of their findings.
LOC: Low.
Based on the body of evidence evaluated in this review there is no reliable evidence that
homeopathy is more effective than placebo for the treatment of people with sinusitis.
Table 65 Evidence summary table: the effectiveness of homeopathy for the treatment of sinusitis
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Bellavite et al Zabolotnyi et al Patients with Homeopathic Placebo Symptoms Significant improvement over Good positive evidence
(2011) (2007) maxillary sinusitis complex Sinfrontal placebo (p-value not reported) for Euphorbium
[Level I] [Level II] compositum in rhinitis-
AMSTAR: 5/10 Quality not sinusitis. Positive
specified evidence from one Level
SR of homeopathy N=113 II study
for multiple
Weiser and Clasen Patients with Euphorbium Placebo Overall Significantly greater
conditions
(1994) chronic sinusitis compositum percentage improvement in homeopathy
[Level II] improvement group (21.1%) compared to
Quality not placebo (14.4%) (p=0.016)
specified
N=155
Wiesenauer et al Patients with Low-dilution (3x-4x) Placebo Global evaluation No effect over placebo
(1989) sinusitis homeopathic and symptoms
[Level II] complex Luffa,
Quality not Cinnabaris, Kalium
specified bichromicum
N=152
Cucherat et al Weiser and Clasen Patients with Euphorbium Placebo Overall Significant difference in favour “It is clear that the
(2000) (1994) chronic sinusitis compositum S nasal percentage of homeopathy (p=0.016) strength of available
[Level I] [Level II] spray improvement evidence is insufficient to
AMSTAR: 10/11 Quality not conclude that
specified homeopathy is clinically
SR of homeopathy N=155 effective.”
for multiple
conditions (Note: this conclusion
refers to all clinical
conditions and is not
specific to sinusitis)
Table 66 Matrix indicating the studies that were included in the systematic reviews of upper respiratory tract infection
Study ID
Steinsbekk Steinsbekk de Lange Lecoq Haidvogl et Rabe et al Riley et al
et al et al et al (1985) al (2007) (2004) (2001)
(2007) (2005) (1994) [Level II] [Level III-2] [Level III- [Level III-
[Level II] [Level II] [Level II] 2] 2]
Altunc et
al (2007)
[Level I]
Systematic review
Linde and
Melchart
(1998)
[Level I]
Bellavite
et al
(2011)
[Level
I/III]
Altunc et al (2007) (AMSTAR score 6/10) performed a systematic review to assess the efficacy of
homeopathy in various conditions that commonly affect children and adolescents, including URTIs.
Two Level II studies were identified for the treatment of URTI. The authors noted that both
Steinsbekk et al (2005) (Jadad score of 5) and de Lange et al (1994) (Jadad score of 3) were double-
blind Level II studies that examined the effect of homeopathy compared to placebo in children aged
3 to 4 years with URTI. Neither of the studies reported significant differences compared with placebo
for the main outcome measures, which included daily symptom scores. Altunc et al (2007) concluded
that “the evidence from rigorous clinical trials of any type of therapeutic or preventive intervention
testing homeopathy for childhood and adolescence ailments is not convincing enough for
recommendations in any condition”.
Linde and Melchart (1998) (AMSTAR score 8/11) aimed to give an overview of the methods and
results of the available Level II studies of individualised homeopathy for a range of clinical conditions.
It included only de Lange et al (1994) (Jadad score 5) for the URTI indication (Steinsbekk et al (2005)
was published after the time of the systematic review). Linde and Melchart (1998) reported that de
Lange et al (1994) found “trends in favour of homeopathy” but no statistically significant differences
between homeopathy and placebo in the number of patients assessed globally as improved (RR 1.08;
95% CI 0.81, 1.42). Overall, Linde and Melchart (1998) concluded that, across all clinical conditions,
any evidence suggesting that homeopathy has an effect over placebo is “not convincing because of
methodological shortcomings and inconsistencies”.
The systematic review by Bellavite et al (2011) (AMSTAR score 5/10) aimed to evaluate the
effectiveness of homeopathy for the treatment of a range of diseases including common upper
respiratory tract infections. Three Level II (de Lange et al, 1994; Lecoq, 1985; Steinsbekk et al, 2007)
and three Level III-2 studies (Haidvogl et al, 2007; Oberbaum et al, 2001; Rabe et al, 2004) were
included in the review for URTIs; however, the quality of the studies was not formally assessed by the
authors of the systematic review. Steinsbekk et al (2007) tested the effect of individualised
homeopathy compared with parents-selected medicines in children with URTI. The study reported no
significant difference in the prevention of new symptoms and symptom scores between the two
methods of prescription. Similar to the systematic review by Altunc et al (2007), Bellavite et al (2011)
also reported no significant difference between the homeopathy and placebo groups (based on the
mean number of infective episodes) in de Lange et al (1994). However, it was noted that the
percentage of children who did not require antibiotics was higher in the homeopathy group (62%)
compared to placebo (49%). The third included Level II study (Lecoq, 1985) investigated the effect of
a homeopathic complex in patients with URTI compared with placebo. Whilst the statistical
significance of the results was not reported, Bellavite et al (2011) noted that “patients rated more
relief in verum group”.
Amongst the three Level III-2 studies, both Haidvogl et al (2007) and Rabe et al (2004) assessed the
effect of homeopathy compared with various conventional therapies (including anti-inflammatory
drugs and antibiotics) in patients with URTI. In Haidvogl et al (2007), it was reported that
homeopathic treatment was not inferior to standard treatments (e.g. anti-inflammatory drugs and
antibiotics) and was best tolerated. Rabe et al (2004) reported equivalence between homeopathy
and anti-inflammatory agents. The third included Level III-2 study (Riley et al, 2001) tested the effect
of individualised homeopathy compared with conventional therapies in patients with respiratory
tract complaints or ear complaints. Thus, the evidence reviewer notes that the patient population
may not be exclusive to those with an URTI. The significance of the results was not specified, but
healing or major improvement after 14 days of treatment was observed in 82.6% of patients in the
homeopathy group and 68% in the conventional treatment group. The rate of adverse events was
7.8% in the homeopathy group and 22.3% in the conventional treatment group. Overall, Bellavite et
al (2011) concluded that “the evidence for individualised homeopathy for upper respiratory tract
infections is defined as conflicting, but if we exclude from consideration the trials of de Lange and
coworkers (trend to positive effect, but not statistically significant) and of Steinsbekk (where the self-
treatment was investigated), a “good” positive evidence in favour of homeopathy can be suggested
in these conditions”.
Reviewer comments
The evidence reviewer notes that the systematic reviews provided contradicting reports of the results
of de Lange et al (1994). Nevertheless, none of the reviews stated an effect of homeopathy in the
treatment of URTI in this Level II study. It is also of interest to note that Altunc et al (2007) rated de
Lange et al (1994) a Jadad quality score of 3, in comparison to Linde and Melchart (1998), who gave a
Jadad quality score of 5 (good quality).
Evidence statement
Three systematic reviews of poor to medium quality identified three randomised controlled trials
(unreported or medium to good quality; total of 486 participants, range: 60-251) that compared
homeopathy with placebo for the treatment of people with upper respiratory tract infections.
The one medium-sized, good-quality trial (251 participants) did not detect a difference between
homeopathy and placebo in the treatment of children with upper respiratory tract infection. LOC:
Low - moderate.
Based on the body of evidence evaluated in this review homeopathy is not more effective than
placebo for the treatment of people with upper respiratory tract infection.
One systematic review of poor quality identified one medium-sized randomised controlled trial
(quality not reported; 208 participants) and three prospectively designed, non-randomised
controlled studies (quality not reported; total of 2498 participants, range: 456-1557) that compared
homeopathy with other therapies (including anti-inflammatory drugs and antibiotics) for the
treatment of people with upper respiratory tract infections.
These studies are of insufficient quality to warrant further consideration of their findings. LOC: Low.
Based on the body of evidence evaluated in this review there is no reliable evidence that
homeopathy is as effective as the other therapies for the treatment of people with upper respiratory
tract infection.
Table 67 Evidence summary table: the effectiveness of homeopathy for the treatment of upper respiratory tract infection
Study ID Included study Patient Intervention Comparator Outcome Results as Systematic review
Level of Level of population reported in the interpretation
a a
evidence evidence systematic
b c review
Quality Quality
Sample size
Altunc et al Steinsbekk et al, Children with Calcarea carbonica, Pulsatilla, Placebo Total daily No significant “The evidence from
(2007) (2005) URTI sulfur in C30 potency; 2 pills 2 symptom score difference rigorous clinical trials of
[Level I] [Level II] Mean age 3.6 years days per week for 12 weeks. In any type of therapeutic or
d 41% male addition, 1 pill up to once every Adverse events “Mild and preventive intervention
AMSTAR: Jadad score 5
Concomitant hour if the child had an acute transient” adverse testing homeopathy for
6/10 N=251
treatment: episode of URTI but reduce the events in 4 placebo childhood and
antibiotics, intake if the URTI was mild or and 9 homeopathy adolescence ailments is
SR of painkiller/ patients
homeopathy when there was an improvement not convincing enough for
antipyretic drugs if
for multiple needed recommendations in any
conditions condition”
de Lange et al Children with Individualised homeopathy. Placebo Daily symptom No significant
(1994) recurrent URTI Remedies in various potencies, scores difference
[Level II] Mean age 4.2 years mainly D6, D30 and D200
d 56% male (remedies not reported) for 1 Number of No significant
Jadad score 3
Concomitant year. Homeopathic medicines antibiotic difference
N=170 treatment courses
treatment: adequate and follow up prescriptions were
nutrition advice, based on the clinical course
antibiotics, Adenoidectomies No significant
adenoidectomy, and tonsillectomies difference
tonsillectomy if after 1 year follow
needed up
Linde and de Lange et al Patients with Constitutional and acute Placebo Number of patients RR 1.08 (95% CI A meta-analysis found an
Melchart (1994) recurrent upper individual simillimum as assessed globally as 0.81,1.42) overall trend in favour of
(1998) [Level II] respiratory tract necessary (changes possible, improved “Trends in favour of homeopathy. The rate
d
[Level I] Jadad score 5 infection dosage and potency variable) homeopathy” ratio was 1.62 (95% CI
AMSTAR: N=175 Median age: 4.2 Intervention group: 1.17, 2.23) and the odds
8/11 years 48/88 (55%) ratio was 2.62.
53% male Control group: 44/87
(51%)
Study ID Included study Patient Intervention Comparator Outcome Results as Systematic review
Level of Level of population reported in the interpretation
a a
evidence evidence systematic
b c review
Quality Quality
Sample size
SR of Difference in daily RR 0.41 (95% CI
homeopathy symptom score 0.02, 0.83) The pooled rate ratio of
for multiple “Trends in favour of the methodologically best
conditions homeopathy” studies was clearly smaller
and not statistically
significant (RR 1.12; 95%
CI 0.87, 1.44)
Bellavite et Steinsbekk et al Children with Individualised homeopathy Parents-selected Total daily No difference “The evidence for
al (2011) (2007) upper respiratory medicines symptom score between groups individualized
[Level I/III] [Level II] tract infections homeopathy for upper
AMSTAR: Quality not respiratory tract infections
Prevention of new No difference
5/10 specified is defined as conflicting,
episodes between the two
N=208 but if we exclude from
methods of
SR of consideration the trials of
prescription
homeopathy de Lange and coworkers
for multiple de Lange et al Children with Individualised homeopathy Placebo Mean number of No significant inter- (trend to positive effect,
conditions (1994) pharyngitis or infective episodes group differences: but not statistically
[Level II] tonsillitis Homeopathy group: significant) and of
Quality not 7.9/year Steinsbekk (where the
specified Placebo group: self-treatment was
8.4/year investigated), a “good”
N=170
Percentage of Significance of positive evidence in favour
children not results not reported of homeopathy can be
suggested in these
requiring Homeopathy group:
antibiotics 62% conditions”
Placebo group: 49%
Study ID Included study Patient Intervention Comparator Outcome Results as Systematic review
Level of Level of population reported in the interpretation
a a
evidence evidence systematic
b c review
Quality Quality
Sample size
Lecoq (1985) Patients with Homeopathic complex L52 Placebo Symptom severity Patients rated more
[Level II] upper respiratory score relief in
Quality not tract infections homeopathy group
specified
N=60
Rabe et al (2004) Patients with Homeopathic complex Gripp- Anti- Symptoms Equivalence
[Level III-2] mild upper heel inflammatory between
Quality not respiratory tract agents homeopathy and
specified infections anti-inflammatory
N=485 agents
Riley et al (2001) Patients with Individualised homeopathy Conventional Healing or major Significance of
[Level III-2] respiratory tract medicine improvement after results not reported
Quality not complaints or ear 14 days of Homeopathy group:
specified complaints treatment 82.6%
Conventional
N=456
medicine group:
68%
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; C, centesimal; CI, confidence interval; D, decimal; RR, relative risk; SR, systematic review; URTI, upper respiratory tract
infection.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
d
The Jadad scale assesses the quality of published clinical trials based methods relevant to random assignment, double blinding and the flow of patients. The range of possible scores is zero
(bad quality) to 5 (good quality).
Evidence statement
One systematic review of medium quality identified one very small randomised controlled trial (poor
quality; 30 participants) that compared homeopathy (Simillimum) with placebo for the treatment of
people with acne vulgaris. LOC: Very low.
Based on only one very small poor quality study there is no reliable evidence on which to draw a
conclusion about the effectiveness of homeopathy compared to placebo for the treatment of people
with acne vulgaris.
Table 68 Evidence summary table: the effectiveness of homeopathy for the treatment of acne vulgaris
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Linde and McDavid (1994) Patients with acne Individualised Placebo Number of patients No significant difference between “Insufficient report”
Melchart (1998) [Level II] vulgaris simillimum with improvement treatment groups.
d in global
[Level I] Quality: 2,3 Intervention group: 9/15 (60%); “Trial seems to be of
AMSTAR: 8/11 N=30 assessment Control group: 11/15 (73%). acceptable quality”
(patient-reported) Rate ratio (95% CI): 0.82 (0.49, 1.37)
SR of
homeopathy for
multiple
conditions
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; CI, confidence interval; SR, systematic review.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
d
Quality assessed using (i) Jadad score (out of 5); (ii) internal validity score (out of 6).
Evidence statement
One systematic review of good quality identified one very small randomised controlled trial (quality
not reported; 46 participants) that compared homeopathy (Hepar sulfuris calcareum) with placebo
for the treatment of people with boils and pyoderma. LOC: Very low.
Based on only one very small study of unknown quality there is no reliable evidence on which to
draw a conclusion about the effectiveness of homeopathy compared to placebo for the treatment of
people with boils and pyoderma.
Table 69 Evidence summary table: the effectiveness of homeopathy for the treatment of boils and pyoderma
Study ID Included study Patient Intervention Comparator Outcome Results as reported in Systematic review interpretation
Level of Level of population the systematic review
a a
evidence evidence
b c
Quality Quality
Sample size
Cucherat (2000) Mossinger (1980) Patients with boils Hepar sulfuris Placebo Healing time No significant difference “It is clear that the strength of available
[Level I] [Level II] and pyoderma calcareum D4 (p=0.318) evidence is insufficient to conclude that
AMSTAR: 10/11 Quality not homeopathy is clinically effective”
specified
d
SR of N=46 (Note: this conclusion refers to all clinical
homeopathy for conditions and is not specific to boils and
multiple pyoderma)
conditions
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; D, decimal; SR, systematic review.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
d
N equals the number of participants evaluated. The number of participants randomised was not reported.
4.15.3 Bruising
The effectiveness of homeopathy for the treatment of patients with bruising was assessed in one
systematic review (Ernst and Pittler, 1998; AMSTAR score 6/10) as summarised in Table 70. Ernst and
Pittler (1998) aimed to review the clinical efficacy of homeopathic Arnica in a range of clinical areas,
and identified two Level III-2 studies that had examined the effect of this treatment in healthy
volunteers with experimentally inflicted mechanical bruising (Campbell, 1976; Savage and Roe,
1978). Both of these trials were very small and rated as low quality by the systematic reviewers. Ernst
and Pittler (1998) reported that in both studies “results numerically favoured Arnica” over placebo
with regards to the extent of bruising and the subjective symptoms outcomes. However, their overall
conclusion across the various clinical conditions they assessed was that “the hypothesis claiming that
homeopathic Arnica is clinically effective beyond a placebo effect is not based on methodologically
sound placebo-controlled trials”.
Evidence statement
One systematic review of medium quality identified two prospectively designed, non-randomised
controlled studies (poor quality; 10 and 13 participants) that compared homeopathy (Arnica) with
placebo for the treatment of people with bruising.
These studies are of insufficient quality and size to warrant further consideration of their findings.
LOC: Very low.
Based on the body of evidence evaluated in this review there is no reliable evidence that
homeopathy is more effective than placebo for the treatment of people with bruising.
Table 70 Evidence summary table: the effectiveness of homeopathy for the treatment of bruising
Study ID Included study Patient Intervention Comparator Outcome Results as reported Systematic review
Level of Level of population in the systematic interpretation
a a
evidence evidence review
b c
Quality Quality
Sample size
Ernst and Pittler Savage and Roe Healthy volunteers Arnica 30C, one tablet Placebo Extent of bruising Results numerically “The claim that homeopathic
(1998) (1978) for the treatment before being bruised and favoured Arnica Arnica is efficacious beyond a
[Level I/III] [Level III-2] of experimentally 2 after, on the same day, placebo effect is not
d
inflicted mechanical and 2 more tablets on Subjective Results numerically supported by rigorous clinical
AMSTAR: 6/10 Jadad score 2
bruising the next day symptoms favoured Arnica trials”
N=10
SR of
Campbell (1976) Healthy volunteers Arnica 10M, one tablet Placebo Extent of bruising Results numerically “The hypothesis claiming
homeopathy for
[Level III-2] for the treatment before being bruised and favoured Arnica that homeopathic Arnica is
multiple d
Jadad score 1 of experimentally 2 after, on the same day, clinically effective beyond a
conditions Subjective Results numerically
N=13 inflicted mechanical and 2 more tablets on placebo effect is not based
bruising the next day symptoms favoured Arnica
on methodologically sound
placebo-controlled trials”.
Evidence statement
One systematic review (2000) did not identify any prospectively designed and controlled studies that
assessed the effectiveness of homeopathy compared with placebo for the treatment of people with
second and third degree burns.
One systematic review of good quality identified one small randomised controlled trial (quality not
reported; 103 participants) that compared homeopathy (Calendula) with Vaseline for the treatment
of people with second and third degree burns. LOC: Very low.
Based on only one small study of unknown quality there is no reliable evidence on which to draw a
conclusion about the effectiveness of homeopathy compared to Vaseline for the treatment of people
with second and third degree burns.
Table 71 Evidence summary table: the effectiveness of homeopathy for the treatment of second and third degree burns
Study ID Included study Patient population Intervention Comparator Outcome Results as reported Systematic review
Level of Level of in the systematic interpretation
a a
evidence evidence review
b c
Quality Quality
Sample size
Cucherat et al Lievre (1992) Patients with second Calendula Vaseline Composite criteria of No significant “It is clear that the strength of
(2000) [Level II] and third degree treatment success difference (p=0.147) available evidence is insufficient to
[Level I] Quality not burns conclude that homeopathy is
AMSTAR: 10/11 specified clinically effective”
N=103
SR of (Note: this conclusion refers to all
homeopathy for clinical conditions and is not specific
multiple to second and third degree burns)
conditions
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; SR, systematic review.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
4.15.5 Eczema
The effectiveness of homeopathy for the treatment of patients with eczema was assessed in two
Level I/III systematic reviews as summarised in Table 73. Both systematic reviews included one Level
II study (Siebenwirth et al, 2009) and two Level III-2 studies (Keil et al, 2008; Witt et al, 2009) (Table
72). Neither of the systematic reviews performed a meta-analysis of the data.
Table 72 Matrix indicating the studies that were included in the systematic reviews of eczema
Study ID
Siebenwirth et al (2009) Witt et al (2009) Keil et al (2008)
[Level II] [Level III-2] [Level III-2]
Ernst (2012)
Systematic
[Level I/III]
review
Simonart et al (2011)
[Level I/III]
Ernst (2012) (AMSTAR score 6/10) performed a systematic review of evidence from controlled clinical
trials of any type of homeopathic treatment for any type of eczema. The one Level II study that was
identified (Siebenwirth et al, 2009; Jadad score 3) examined the effect of individualised homeopathic
treatment in patients with atopic eczema. Ernst (2012) reported that it found a non-significant trend
that favoured placebo over homeopathy. Two Level III-2 studies each with a Jadad score of 1 were
also included. Both Witt et al (2009) and Keil et al (2008) examined the effect of treatment by
homeopaths in children with eczema compared with conventional treatment (including
corticosteroids and antihistamines). The study found no significant difference between homeopathy
and conventional treatment in either symptom scores or quality of life in both trials. Ernst (2012)
concluded that “the available data do not demonstrate homeopathic remedies to be efficacious as a
treatment of eczema”.
Simonart et al (2011) (AMSTAR score 8/10) conducted a systematic review of evidence for the
efficacy of homeopathic treatments in dermatology. A number of different dermatological conditions
were examined, including atopic dermatitis (a form of eczema), which included the same three
studies as Ernst (2012). Simonart et al (2011) reported no significant difference between
homeopathy and the comparator (which was placebo in one of the trials and unspecified
‘conventional therapy’ in the other two trials) for any of the outcomes examined in Siebenwirth et al
(2009), Witt et al (2009) or Keil et al (2008). The only exception was in Keil et al (2008), where a
significant difference (p<0.001) was reported for the extent of improvement of signs/symptoms of
eczema as assessed by the physician. However, it is unclear if this difference favoured homeopathy
or the other therapy (the other therapy was not specified in Simonart et al, 2011). Simonart et al
(2011) also noted some of the limitations of the included trials. Siebenwirth et al (2009) had a high
percentage of ineligible patients and a high proportion of dropouts. The patient population in both
Keil et al (2008) and Witt et al (2009) were recruited at the homeopathic or conventional doctor’s
practices, which presents a bias as the patients had already made their own choice of preferred
therapeutic approach. Further, the use of conventional therapies was allowed in the homeopathic
group in Witt et al (2009), which would make it difficult to ascertain any effect of homeopathic
treatment. Simonart et al (2011) concluded that “the hypothesis that any dermatological condition
Evidence statement
Two systematic reviews of medium quality identified one very small randomised controlled trial
(medium quality; 24 participants) that compared homeopathy with placebo for the treatment of
people with eczema. LOC: Very low.
Based on only one very small study there is no reliable evidence on which to draw a conclusion about
the effectiveness of homeopathy compared to placebo for the treatment of people with eczema.
Two systematic reviews of medium quality identified two prospectively designed, non-randomised
controlled studies (poor quality; 118 and 135 participants) that compared homeopathy with other
therapies (corticosteroids, antihistamines and other unspecified therapies) for the treatment of
people with eczema.
These studies are of insufficient quality and power to warrant further consideration of their findings.
LOC: Very low.
Based on the body of evidence evaluated in this review there is no reliable evidence that
homeopathy is as effective as the other therapies for the treatment of people with eczema.
Table 73 Evidence summary table: the effectiveness of homeopathy for the treatment of eczema
Study ID Included study Patient Intervention Comparator Outcome Results as reported in Systematic review
Level of Level of population the systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Ernst (2012) Siebenwirth et al Patients with Individualised Placebo Not reported A non-significant trend “The available data do not
[Level I/III] (2009) atopic eczema homeopathic favoured placebo over demonstrate homeopathic
AMSTAR: 6/10 [Level II] treatment for homeopathy remedies to be efficacious as a
d
Jadad score 3 32 weeks treatment of eczema”
SR of N=24
homeopathy for
Witt et al (2009) Children with Treatment by Conventional Symptom scores No significant difference
eczema
[Level III-2] atopic eczema homeopaths treatment
d (not specified)
Jadad score 1
N=135 Quality of life No significant difference
Keil et al (2008) Children with Treatment by Conventional Symptom scores No significant difference
[Level III-2] eczema homeopaths treatment
d (not specified)
Jadad score 1
Quality of life No significant difference
N=118
Simonart et al Siebenwirth et al Young adults Individually Placebo MP score No significant difference “The hypothesis that any
(2011) (2009) aged 18-35 selected dermatological condition
[Level I/III] [Level II] years with homeopathic responds convincingly better to
atopic remedies for 32 Quality of life No significant difference homeopathic treatment than to
AMSTAR: 8/10 Quality not
specified dermatitis weeks placebo or other control
SR of N=24 interventions is not supported
Coping and global No significant difference
homeopathy for by evidence”.
assessments of
multiple treatment success
conditions (Note: this conclusion refers to
Witt et al (2009) Children aged Individually Conventional SCORAD No significant difference all clinical conditions and is not
[Level III-2] 1-14 years with selected therapy specific to eczema)
Quality not atopic homeopathic
specified dermatitis remedies for 12
N=135 months
Study ID Included study Patient Intervention Comparator Outcome Results as reported in Systematic review
Level of Level of population the systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Keil et al (2008) Children less Individually Conventional Extent of improvement No significant difference
[Level III-2] than 17 years selected therapy of signs/symptoms of
Quality not of age with homeopathic eczema as assessed by
specified atopic remedies for 12 the patients or their
N=118 dermatitis months parents on a 0-10
numerical scale
Evidence statement
One systematic review of medium quality identified one very small randomised controlled trial
(quality not reported; 41 participants) that compared homeopathy with placebo for the treatment of
people with seborrhoeic dermatitis. LOC: Very low.
Based on only one very small study of unknown quality there is no reliable evidence on which to
draw a conclusion about the effectiveness of homeopathy compared to placebo for the treatment of
people with seborrhoeic dermatitis.
Table 74 Evidence summary table: the effectiveness of homeopathy for the treatment of seborrhoeic dermatitis
Study Included studies Patient Intervention Comparator Outcomes Results Systematic review
a
Level of evidence Level of population interpretation
b a
Quality evidence
c
Quality
Sample size
Simonart et al, 2011 Smith et al, 2002 Patients aged 20-77 Homeopathic mineral Placebo SASI Significant difference in “The hypothesis that any
[Level I] [Level II] years with typical therapy (potassium improvement favour of homeopathy dermatological condition
AMSTAR: 8/10 Quality not seborrhoeic bromide 1X, sodium (p=0.03) responds convincingly
specified dermatitis or bromide 2X, nickel SASI improvement 3842% in better to homeopathic
SR of homeopathy N=41 dandruff sulphate 3X, sodium homeopathy group treatment than to placebo
chloride 6X) for 10 and -1066% in placebo group or other control
for multiple
conditions weeks interventions is not
supported by evidence”.
4.15.7 Ulcers
The effectiveness of homeopathy for the treatment of patients with ulcers was assessed in two
systematic reviews as summarised in Table 76. In total, the systematic reviews included one Level II
study and one Level III-2 study (Table 75). Neither of the systematic reviews specified the quality of
the included studies.
Table 75 Matrix indicating the studies that were included in the systematic reviews of ulcers
Study ID
Mousavi et al (2009) Garrett et al (1997)
[Level II] [Level III-2]
Bellavite et al (2011)
Systematic
[Level I]
review
Simonart et al (2011)
[Level I/III]
The systematic review by Bellavite et al (2011) (AMSTAR score 5/10) aimed to evaluate the
effectiveness of homeopathy for the treatment of a range of diseases including infections of the
upper airways and ear-nose-throat ailments. One Level II study was identified for aphthous ulcers.
Mousavi et al (2009) was a single-(patient) blind Level II study that investigated the efficacy of
individualised homeopathy in the treatment of patients with minor recurrent aphthous ulceration for
6 days. The study found that pain intensity and ulcer size were significantly lower in the homeopathy
group compared with placebo at day 4 and day 6 of treatment (p<0.05). Bellavite et al (2011) did not
formulate an overall conclusion on the effectiveness of homeopathy for the treatment of ulcers.
Simonart et al (2011) (AMSTAR score 8/10) aimed to assess the evidence for the efficacy of
homeopathic treatments in dermatology. For the ulcers indication, two relevant Level II studies of
unspecified quality were identified. Consistent with Bellavite et al (2011), Simonart et al (2011) also
reported a significant effect of homeopathy in the Level II study by Mousavi et al (2009). However,
Simonart et al (2011) noted that “the open-label design is the major limitation of this study”, which
may have subjected the results to bias. Garrett et al (1997) was a small, Level III-2 study that
investigated the effect of homeopathy in patients with leg ulcers. Of importance, each patient had
conventional local or systemic therapy continued during the trial period. The study reported no
significant difference in improvement in ulcer size between the homeopathy and placebo groups.
Simonart et al (2011) noted that poor randomisation, small sample size, inadequate statistical
methodology and the absence of blinding were the major limitations of this study. Overall, Simonart
et al (2011) concluded that “the hypothesis that any dermatological condition responds convincingly
better to homeopathic treatment than to placebo or other control interventions is not supported by
evidence”.
Evidence statement
Two systematic reviews of poor and medium quality identified one small randomised controlled trial
(quality not reported; 100 participants) and one very small prospectively designed, non-randomised
controlled study (quality not reported; 23 participants) that compared homeopathy with placebo for
the treatment of people with ulcers.
These studies are of insufficient quality and size to warrant further consideration of their findings.
LOC: Very low - low.
Based on the body of evidence evaluated in this review there is no reliable evidence that
homeopathy is more effective than placebo for the treatment of people with ulcers.
Table 76 Evidence summary table: the effectiveness of homeopathy for the treatment of ulcers
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Bellavite et al Mousavi et al Patients with Individualised Placebo Improvement in Significant improvement in the No final conclusions were
(2011) (2009) minor aphthous homeopathy ulcer size and homeopathy group at day 4 drawn
[Level I] [Level II] ulcer mean pain score and day 6 of treatment
AMSTAR: 5/10 Quality not (p<0.05)
specified
SR of N=100
homeopathy for
multiple
conditions
Simonart et al Mousavi et al Patients aged Individually Placebo Improvement in Significant difference in favour “The hypothesis that any
(2011) (2009) 18-65 years selected ulcer size of homeopathy (p<0.05) dermatological condition
[Level I/III] [Level II] with 1-5 homeopathic Proportion of responders: 96% in responds convincingly better to
AMSTAR: 8/10 Quality not aphthous ulcers remedies (two homeopathy group and 72% in homeopathic treatment than
specified of <24 hours doses) for 6 days placebo to placebo or other control
SR of N=100 duration Mean pain score Significant difference in favour interventions is not supported
homeopathy for of homeopathy (lower pain by evidence”
multiple intensity) (p<0.05)
conditions (Note: this conclusion refers to
Garrett et al Patients aged Sulphur, silica and Placebo Improvement in No significant difference all clinical conditions and is not
(1997) 53-87 years carbo-vegetabilis 6 ulcer size specific to ulcers)
[Level III-2] with leg ulcers cH for a mean
Quality not duration of 4.2
specified weeks
N=23
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; cH, Hahnemannian centesimal scale; VAS, visual analogue scale.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
Evidence statement
One systematic review of medium quality identified one very small randomised controlled trial
(quality not reported; 28 participants) that compared homeopathy with placebo for the treatment of
people with uraemic pruritis. LOC: Very low.
Based on only one very small study of unknown quality there is no reliable evidence on which to
draw a conclusion about the effectiveness of homeopathy compared to placebo for the treatment of
people with uraemic pruritis.
Table 77 Evidence summary table: the effectiveness of homeopathy for the treatment of uraemic pruritis
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Simonart et al Cavalcanti et al Patients with Individually Placebo Percentage of No significant difference “The hypothesis that any
(2011) (2003) uraemic pruritis selected maximum pruritis score dermatological condition
[Level I] [Level II] homeopathic before and during responds convincingly
AMSTAR: 8/10 Quality not remedies for 2 treatment better to homeopathic
specified months treatment than to
Percentage of Significant difference in favour of placebo or other control
SR of homeopathy N=28 responders (>50% homeopathy (p=0.038)
for multiple interventions is not
reduction in pruritis 0% responders in placebo group, 45% supported by evidence”
conditions score) responders in homeopathy group after
30 days
(Note: this conclusion
No significant difference (p=0.370) refers to all clinical
7/11 responders in homeopathy group conditions and is not
3/9 responders in placebo group specific to uraemic
Pruritus score No significant difference (p=0.260) pruritis)
38 ± 33 in homeopathy group
57 ± 39 in placebo group
4.15.9 Warts
The effectiveness of homeopathy for the treatment of patients with warts was assessed in four
systematic reviews as summarised in Table 79. In total, the systematic reviews included two Level II
studies (Kainz et al, 1996; Labrecque et al, 1992) and one Level III-2 study (Villeda et al, 2001) (Table
78). One systematic review (Linde and Melchart, 1998) performed a meta-analysis of the data;
however it included a variety of clinical conditions and was not specific to warts.
Table 78 Matrix indicating the studies that were included in the systematic reviews of warts
Study ID
Kainz et al (1996) Labrecque et al Villeda et al (2001)
[Level II] (1992) [Level III-2]
[Level II]
Loo and Tang (2009)
[Level I]
Systematic review
Altunc et al (2007)
[Level I]
Loo and Tang (2009) (AMSTAR score 6/10) performed a systematic review of the effects of
treatments for non-genital warts. For homeopathy as a treatment, it included the results of two poor
quality Level II studies (Kainz et al, 1996; Labrecque et al, 1992). In both studies, there was no
significant difference in the proportion of participants with wart clearance between the homeopathy
and placebo groups. In Labrecque et al (1992), there was also no significant difference in adverse
effects experienced by participants in the homeopathy and placebo groups. As a result, Loo and Tang
(2009) concluded that “we don’t know whether homeopathy increases cure rates compared with
placebo, as few high-quality studies have been found” and “we don’t know whether homeopathy is
more effective at increasing the proportion of people with wart clearance after 8-18 weeks”.
Altunc et al (2007) (AMSTAR score 6/10) performed a systematic review to assess the efficacy of
homeopathy in various conditions that commonly affect children and adolescents, including warts.
One Level II study given a Jadad score of 4 (Kainz et al, 1996) was identified for the treatment of
warts. The systematic review noted that this Level II study “failed to demonstrate the effectiveness of
individualised homeopathic treatment for reducing the size of warts”. It concluded that “the
evidence from rigorous clinical trials of any type of therapeutic or preventive intervention testing
homeopathy for childhood and adolescence ailments is not convincing enough for recommendations
in any condition”.
Linde and Melchart (1998) (AMSTAR score 8/11) performed a systematic review of the efficacy of
individualised homeopathy across a range of clinical conditions. They identified the same Level II
study by Kainz et al (1996) (given a Jadad score of 4) that has been discussed above. Linde and
Melchart (1998) reported that 27% of participants treated with homeopathy achieved at least a 50%
reduction in the size of warts, compared to 21% of patients who received placebo. The
Prepared for the NHMRC Homeopathy Working Committee by Optum 233
EFFECTIVENESS OF HOMEOPATHY FOR CLINICAL CONDITIONS: OVERVIEW REPORT October 2013
corresponding rate ratio was 1.29 (95% CI 0.55, 3.00), indicating no significant difference between
the treatment groups. The authors of the systematic review were critical of the fact that the trial only
had one outcome measure and that some details were lacking in the report. They also stated that the
study suffered from a lack of statistical power.
Simonart and De Maertelaer (2012) (AMSTAR score 6/10) is a systematic review that assessed the
evidence for the efficacy of systemic treatments for cutaneous warts. It included two Level II studies
(Kainz et al, 1996; Labrecque et al, 1992) and also one Level III-2 study (Villeda et al, 2001). Whilst the
quality of the individual studies was not specified, comment was made that “many of the trials
reviewed concerning systemic treatment for cutaneous warts were of limited quality”. In all three
included studies, there was no significant difference in the complete clearance of warts between the
homeopathy and placebo groups. In Labrecque et al (1992), there was also no significant difference
in adverse effects experienced by participants in the homeopathy and placebo groups. Simonart and
De Maertelaer (2012) concluded that “evidence for the efficacy of homeopathy is lacking”.
Reviewer comments
The evidence reviewer notes that one of the Level II studies (Kainz et al, 1996) was given a Jadad
score of 4 by Linde and Melchart (1998) and Altunc et al (2007); however, Loo and Tang (2009) stated
that the trial was of “low quality”. There is no apparent reason for the discrepancy between the
reviews.
Evidence statement
Four systematic reviews of medium quality identified two randomised controlled trials (poor to
medium quality; 77 and 174 participants) and one very small prospectively designed, non-
randomised controlled study (quality not reported; 26 participants) that compared homeopathy with
placebo for the treatment of people with warts. LOC: Very low - low.
Based on the body of evidence evaluated in this review homeopathy is not more effective than
placebo for the treatment of people with warts.
Table 79 Evidence summary table: the effectiveness of homeopathy for the treatment of warts
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Loo and Tang Kainz et al (1996) Not specified. Oral homeopathy Placebo Proportion of No significant difference “We don’t know
(2009) [Level II] Assumed to be (individually selected people with RR 4.85 (95% CI 0.60, 39.35) whether homeopathy
[Level I] Low quality patients with regimen) wart clearance 5/34 (15%) patients in increases cure rates
AMSTAR: 6/10 N=67 non-genital warts homeopathy group, and 1/33 compared with
(3%) patients in placebo group placebo, as few high-
had wart clearance at 8 weeks quality studies have
SR of CAM for
non-genital Labrecque et al Not specified. Oral homeopathy for 6 weeks Placebo Proportion of No significant difference been found.”
warts (1992) Assumed to be (Thuya 30cH plus antimony people with ARR 4% (95% CI -8, 17)
[Level II] patients with crudum 7cH plus nitricium wart clearance 16/80 (20%) patients in
Low quality non-genital warts acidum 7cH) homeopathy group, and 20/82
(24%) patients in placebo group
N=174 had wart clearance at 18 weeks
Altunc et al Kainz et al (1996) Patients with Individualised homeopathy, Placebo Number of No significant difference “A single RCT was
(2007) [Level II] warts. Gender material potencies, 8 weeks responders identified for treating
[Level I] Jadad score 4
d not reported. 10 different remedies were (50% reduction warts. It failed to
AMSTAR: 6/10 N=60 Intervention preselected: sulfur 12X potency, in warts area) demonstrate the
group: mean age Calcium carbonicum 30X effectiveness of
8 years potency, Natrium muriaticum Adverse events Main adverse events include individualised
SR of Control group: mean 30X potency, sepia 12X potency, thrombosis of a capillary
homeopathy homeopathic
age 9 years Causticum 12X potency, hemangioma (1 placebo),
for multiple Staphysagria 12X potency, Thuja
treatment for reducing
exacerbation (1 in both the size of warts”.
conditions 12X potency. Globuli 12X potency
homeopathy and placebo
were administered once a day;
globuli 30X potency every other
groups)
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
day
Linde and Kainz et al (1996) Children (aged 6- Best-fitting simillimum out of Placebo Number of No significant difference “Only one outcome
Melchart (1998) [Level II] 12 years) with predefined set of 10 responders Intervention group: 9/33 (27%); measure; lack of
e common warts constitutional remedies in (50% reduction comparator group: 7/34 (21%) statistical power”.
[Level I] Quality: 4,4
AMSTAR: 8/11 on the hands D12 (once a day) and D30 in warts area)
N=77
(once every other day) Rate ratio (95% CI): 1.29 (0.55,
“Simple,
3.00)
SR of straightforward trial
homeopathy with some details
for multiple lacking in the report”.
conditions
Simonart and Kainz et al (1996) Children aged 6- Homeopathic therapy Placebo Complete No significant difference “Evidence for the
De Maertelaer [Level II] 12 years. (individually selected clearance of Complete clearance of warts in efficacy of
(2012) Quality not Ordinary warts on regimen) for 6 weeks warts 9/30 (30%) patients in homeopathy is lacking”
[Level I/III] specified the back of the intervention group and 7/30
hands only (23%) patients in control group
AMSTAR: 6/10 N=67
Labrecque et al Children and Homeopathic therapy (Thuya Placebo Complete No significant difference
SR of CAM for
(1992) adults. Ordinary 30CH plus antimonium clearance of Complete clearance of warts in
warts
[Level II] warts on the feet crudum 7cH plus nitricium warts 4/74 (5%) patients in intervention
Quality not only acidum 7cH) for 6 weeks group and 4/71 (5%) patients in
control group
specified
N=174 Adverse events No significant difference
Villeda et al (2001) Children and Homeopathic therapy (Thuya Placebo Complete No significant difference
[Level III-2] adults. Ordinary 6cH) for 1 month clearance of Complete clearance of warts in
Quality not warts anywhere warts 1/12 (8%) patients in intervention
specified group and 0/14 (0%) patients in
control group)
N=26
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; ARR, absolute risk reduction; CAM, complementary and alternative medicines; cH, Hahnemannian centesimal scale; CI,
confidence interval; D, decimal; RCT, randomised controlled trial; RR, relative risk; SR, systematic review.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
d
The Jadad scale assesses the quality of published clinical trials based methods relevant to random assignment, double blinding and the flow of patients. The range of possible scores is zero
(bad quality) to 5 (good quality).
Table 80 Matrix indicating the studies that were included in the systematic reviews of chronic fatigue syndrome
Study ID
Saul (2005) Weatherley-Jones Awdry (1996)
[Level II] (2004) [Level II]
[Level II]
Alraek et al (2011)
[Level I]
Davidson et al (2011)
[Level I]
Systematic review
Reid et al (2011)
[Level I]
Porter et al (2010)
[Level I]
Turnbull et al (2007)
[Level I]
Linde and Melchart (1998)
[Level I]
Davidson et al (2011) (AMSTAR score 8/10) conducted a systematic review that examined the
effectiveness of homeopathy for the treatment of a range of clinical conditions, including three Level
II studies (Awdry, 1996; Saul, 2005; Weatherley-Jones, 2004) that examined homeopathy for the
treatment of CFS. The largest trial included 103 patients (Weatherley-Jones, 2004) and was
considered to be of good quality by the authors of the systematic review. Davidson et al (2011)
reported that the Level II study produced “mixed results, but the most rigorous measure supports
homeopathy” and stated there was “weak, but equivocal evidence favouring homeopathy”. The
systematic review also presented results from a “fair quality” Level II study by Awdry (1996), stating
that while homeopathy seemed to be effective on many measures, no statistical analyses were
carried out and “some of the published numbers do not add up in subscales”. Therefore, Davidson et
al (2011) were “guarded in stating advantages for homeopathy” based on Awdry (1996).
The smallest Level II study (Saul, 2005) included 30 CFS patients and was judged to be the
methodologically weakest Level II study by Davidson et al (2011). The study reported no benefit for
individualised homeopathy compared to placebo. Davidson et al (2011) provided a broad conclusion
across all trials that assessed homeopathy for functional somatic syndromes that “all except one of
the six functional somatic syndrome studies yielded positive evidence that homeopathy was superior
to placebo, and that was the smallest and methodologically weakest”.
Alraek et al (2011) (AMSTAR score 7/10) examined the effectiveness of a variety of CAM in relieving
symptoms of CFS. The systematic review included two Level II studies (Weatherley-Jones, 2004;
Awdry, 1996) that examined the effectiveness of homeopathy compared with placebo for six months
and one year, respectively. As reported above, Awdry (1996) did not conduct statistical analyses,
although Alraek et al (2011) reported that Awdry (1996) found “beneficial effects of homeopathy on
symptom improvement”. Weatherley-Jones (2004) found that homeopathy significantly improved
function and fatigue compared to placebo. Across all eight measures of methodological quality
assessed by Alraek et al (2011), Weatherley-Jones (2004) had a low risk of bias, whereas Awdry
(1996) had a mixture of low, unclear and high risk of bias. Overall, Alraek et al (2011) concluded that
homeopathy had “insufficient evidence of symptom improvement in CFS” compared with placebo.
Porter et al (2010) (AMSTAR score 9/10) included the same two Level II studies as Alraek et al (2011)
in their review of CAM for the treatment of several functional somatic syndromes, including CFS. No
additional results were reported, although Porter et al (2010) assessed the quality of the studies
using Jadad scores. Awdry (1996) and Weatherley-Jones (2004) received Jadad scores of 2 and 5,
respectively. Porter et al (2010) concluded that “given the limited number of studies and mixed
outcomes, no conclusions can be drawn on homeopathy for chronic fatigue syndrome”.
Turnbull et al (2007) (AMSTAR score 5/10) also conducted a systematic review of CAM for CFS,
including the same results from the same two Level II studies as Alraek et al (2011) and Porter et al
(2010) (Awdry, 1996; Weatherley-Jones, 2004). Overall, Turnbull et al (2007) concluded that “the
evidence found on the effects of complementary therapies for CFS is inadequate in terms of quantity
and/or quality”.
Similarly, the conclusion from the systematic review of CAM and CFS by Reid et al (2011) was that
“there is insufficient evidence to recommend homeopathy as a treatment in CFS”, based on the Level
II study of “moderate quality” by Weatherley-Jones (2004).
Finally, the much earlier systematic review by Linde and Melchart (1998) (AMSTAR score 8/11) of
homeopathy and multiple clinical conditions only included the older Level II study by Awdry (1996;
Jadad score 3). Linde and Melchart reported results from Awdry (1996) that favoured homeopathy;
however, the systematic review authors stated that although the trial seemed to be rigorous, the
reporting of results was “partly detailed but confusing”. Overall, Linde and Melchart (1998)
concluded that, across all clinical conditions, any evidence suggesting that homeopathy has an effect
over placebo is “not convincing because of methodological shortcomings and inconsistencies”.
Evidence statement
Six systematic reviews of poor to good quality identified three randomised controlled trials (poor to
good quality; total of 197 participants, range: 30-103) that compared homeopathy with placebo for
the treatment of people with chronic fatigue syndrome.
These studies are of insufficient quality and/or size to warrant further consideration of their findings.
LOC: Low.
Based on the body of evidence evaluated in this review there is no reliable evidence that
homeopathy is more effective than placebo for the treatment of people with chronic fatigue
syndrome.
Table 81 Evidence summary table: the effectiveness of homeopathy for the treatment of chronic fatigue syndrome
Study ID Included study Patient population Intervention Comparator Outcome Results as reported in Systematic review
Level of Level of the systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Alraek et al Weatherley-Jones Patients over 18 years Homeopathy for Placebo MFI No significant difference “Compared to placebo,
(2011) (2004) of age diagnosed with 6 months except general fatigue homeopathy had insufficient
[Level I] [Level II] CFS according to the (p=0.04) evidence of symptom
AMSTAR: 7/10 Quality not Oxford criteria improvement in CFS”
FIS No significant difference
specified
SR of CAM for N=93 FLP Significant difference
CFS (p=0.04)
Awdry (1996) Patients less than 65 Homeopathy for Placebo Daily graphs No significant differences
[Level II] years of age diagnosed 1 year completed by each reported (no between-
Quality not with CFS according to patient group analysis)
specified the Oxford criteria
Symptom score No significant differences
N=61 (no between-group
analysis)
Davidson et al Saul (2005) Patients with CFS Individualised Placebo CFS-Q No benefit for homeopathy “All except one of the six
(2011) [Level II] homeopathy functional somatic
F-VAS No benefit for homeopathy syndromes studies yielded
[Level I] Poor quality
AMSTAR: 8/10 N=30 positive evidence that
homeopathy was superior to
Weatherley-Jones Patients with CFS Individualised Placebo MFI scales (general Mixed results, but the most placebo and that one was
SR of
(2004) homeopathy fatigue, physical rigorous measure supports one of the smallest and
homeopathy
[Level II] fatigue, mental homeopathy – no further methodologically weakest”
for multiple
Good quality fatigue, reduced information provided
conditions
N=103 activity, reduced (Note: this conclusion refers
motivation) to all clinical conditions and
Effect size (95% CI) ES (95% CI): 0.40 (-0.03 to is not specific to CFS)
and NNT based on 0.83)
MFI - fatigue NNT: 6.14
Study ID Included study Patient population Intervention Comparator Outcome Results as reported in Systematic review
Level of Level of the systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Effect size (95% CI) ES (95% CI): -0.08 (-0.34 to
based on MFI – 0.50)
reduced motivation
Awdry (1996) Patients with CFS Individualised Placebo Global response Homeopathy group 43%;
[Level II] homeopathy placebo group 4%.
Fair quality “Advantages seem evident
N=64 on many measures, but
statistical analysis not
carried out”
NNT 2.49
Reid et al Weatherley-Jones Adults with CFS (Oxford Individualised Placebo 5 MFI scales: general No significant difference “There is insufficient
(2011) (2004) criteria) homeopath fatigue, physical except general fatigue evidence to recommend
[Level I] [Level II] fatigue, mental (favours homeopathy; homeopathy as a treatment
AMSTAR: 5/10 Moderate quality fatigue, reduced p=0.04) in CFS”
N=103 activity, reduced Homeopathy group: mean
SR of CAM for motivation change 2.7
Placebo group: mean change
CFS 1.35
Porter et al Weatherley-Jones Patients with CFS Homeopathy – Placebo Physical outcomes Positive results for “Given the limited number of
(2010) (2004) details not homeopathy studies and mixed outcomes,
[Level I] [Level II] specified no conclusions can be drawn
d on homeopathy for CFS”
AMSTAR: 9/10 Jadad score 5
N=103
SR of CAM for
Awdry (1996) Patients with CFS Homeopathy – Placebo Overall beneficial Null result for homeopathy
multiple
[Level II[ details not effect or reduction in
conditions d
Jadad score 2 specified symptoms
N=64 Quality of life Null result for homeopathy
Study ID Included study Patient population Intervention Comparator Outcome Results as reported in Systematic review
Level of Level of the systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Turnbull et al Weatherley-Jones Patients aged over 18 Homeopathic Placebo MFI Significant difference for “The evidence found on the
(2007) (2004) years who were consultations the general fatigue scale of effects of complementary
[Level I] [Level II] diagnosed with CFS over a 6 month the MFI (p=0.04) therapies for CFS is
AMSTAR: 5/10 SIGN EL 1++
e using the Oxford period with 26% of patients in treatment inadequate in terms of
N=103 criteria consultations at group showed clinical quantity and/or quality.”
monthly periods improvements on all
SR of CAM for subscales of the MFI
CFS when
compared to 9% of the
individualised
placebo group
prescriptions
were made FIS No significant difference
Awdry (1996) Patients aged less than Variety of Placebo Daily graphs “Cumulative results
[Level II] 65 years who were homeopathic completed by each presented graphically for a
e diagnosed with CFS remedies “as patient small part of the scale - not
SIGN EL 1
N=64 using the Oxford indicated”, clear on how to extract
criteria and had the assessed by data or how meaningful
illness for less than 10 homeopath this is”
years duration
End of trial self- Homeopathy group: 6
assessment charts recovered, 4 greatly
completed by each improved, 3 improved, 6
patient were slightly better and 11
largely unchanged.
Placebo group: 0
recovered, 1 greatly
improved, 0 improved, 4
were slightly better and 26
largely unchanged
Study ID Included study Patient population Intervention Comparator Outcome Results as reported in Systematic review
Level of Level of the systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Linde and Awdry (1996) Patients with postviral Individual Placebo Number of patients Intervention group: 13/32 “Apparently rigorous trial,
Melchart [Level II] fatigue syndrome simillimum assessed globally as (41%); Control group: 1/32 partly detailed but confusing
(1998) f (mean age 40 years; improved (3%). reporting”.
Quality:3,4
[Level I] N=64 70% female) Rate ratio (95% CI): 13.0
AMSTAR: 8/11 (1.81, 93.6) “Homeopathy superior
regarding sleep, fatigue,
SR of disability, mood”.
homeopathy
for multiple
conditions
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; CAM, complementary and alternative medicines; CFS, chronic fatigue syndrome; CFS-Q, Chronic Fatigue Syndrome
Questionnaire; CI, confidence interval; EL, evidence level; F-VAS, Fatigue Visual Analogue Scale; FIS, Fatigue Impact Scale; FLP, Functional Limitations Profile; MFI, Multidimensional Fatigue
Inventory; NNT, number needed to treat; SIGN, Scottish Intercollegiate Guidelines Network; SR, systematic review.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
d
The Jadad scale assesses the quality of published clinical trials based methods relevant to random assignment, double blinding and the flow of patients. The range of possible scores is zero
(bad quality) to 5 (good quality).
e ++
SIGN evidence level assesses the quality of the evidence based on study design and risk of bias. The range of possible scores is 4 (low) to 1 (high). Studies with a level of evidence ‘–‘ should
not be used as a basis for making a recommendation due to high risk of bias.
f
Quality was assessed using two measures (i) Jadad score, out of 5; (ii) internal validity score, out of 6.
Table 82 Matrix indicating the studies that were included in the systematic reviews of sleep or circadian rhythm
disturbances
Systematic reviews
Ernst (2011) Davidson et al Cooper and Linde and
[Level I] (2011) Relton (2010) Melchart
[Level I] [Level I] (1998)
[Level I]
Kumar (2010)
[Level II]
Naude et al (2010)
[Level II]
Kolia-Adam et al
(2008)
[Level II]
La Pine et al (2006)
Study IDs
[Level II]
Cialdella et al
(2001)
[Level II]
Lipman et al (1999)
[Level II]
Wolf (1992)
[Level II]
Carlini et al (1987)
[Level II]
The systematic review by Davidson et al (2011) (AMSTAR score 8/10) examined the effectiveness of
homeopathy in treating a number of clinical conditions, including five Level II studies (Kolia-Adam,
2008; Kumar, 2010; La Pine et al, 2006; Lipman et al, 1999; Naude et al, 2010) that investigated the
effect of various homeopathic remedies on sleep- and circadian rhythm-related problems. The
quality assessment conducted by the authors of the systematic review (using the SIGN assessment
tool) indicated that three of the trials were of “poor” quality (Kolia-Adam, 2008; Kumar, 2010; La Pine
et al, 2006). Of those three trials, one (Kumar, 2010) reported significant results in favour of
homeopathy (p<0.05) on the Profile of Mood Score (fatigue sub-scale). However, the authors noted
that the trial reported inconsistent and ambiguous p-values, so the reliability of those significant
results is not clear. The trials by Kolia-Adam (2008) and La Pine et al (2006) reported no significant
difference between treatment groups for any outcome.
In contrast, the trials by Naude et al (2010) and Lipman et al (1999) were determined to be of “fair”
quality by Davidson et al (2011). Naude studied the efficacy of individualised homeopathy compared
to placebo in patients with primary insomnia and found a statistically significant benefit of
homeopathy compared to placebo according to two outcomes (Sleep diary, p<0.05; Severity of
Insomnia Index, p<0.0001). Similarly, Lipman et al reported a significant improvement (p<0.001) in
Snoring Daily Score in the homeopathy group (80%) compared to placebo (46%).
Overall, Davidson et al (2011) found that there is mixed evidence for the efficacy of homeopathy in
sleep- and circadian rhythm-related problems. The authors stated that their confidence in the results
of the individual trials was either moderate or low and concluded that the cumulative evidence does
not warrant a “positive or a negative overall recommendation for this group”.
Ernst (2011) (AMSTAR score 6/10) performed a systematic review that focused specifically on
homeopathy for insomnia and sleep-related disorders. Three of the studies discussed above (Kolia-
Adam et al, 2008; La Pine et al, 2006; Naude et al, 2010) were also identified for inclusion by Ernst
(2011) and given quality ratings of “poor”, “moderate” and “moderate”, respectively. No significant
differences were reported for any outcome in the three trials; however, Naude et al (2010) did not
report the statistical significance of the difference in total hours of sleep (as measured by the sleep
diary), that favoured homeopathy over placebo. Three additional Level II studies by Carlini et al
(1987), Cialdella et al (2001) and Wolf (1992) investigated the efficacy of various homeopathic
remedies compared to placebo. The specific sleep-related disorder that these trials examined could
not be ascertained from the systematic review. No significant differences were reported between
homeopathy and placebo in any of the three trials for any outcome, including sleep duration, sleep
quality, improvement in night awakenings, or other clinical ratings.
Overall, Ernst (2011) concluded that the best available evidence does not support the notion that
homeopathic remedies are effective for the treatment of insomnia. Ernst (2011) also stated that
proponents of homeopathy should not make claims about positive therapeutic effects until trials
with rigorous study designs and consistently positive findings are available.
The efficacy of homeopathy in patients with insomnia was also investigated in a systematic review by
Cooper and Relton (2010) (AMSTAR score 7/10). The review included four Level II trials (Carlini et al,
1987; Cialdella et al, 2001; Kolia-Adam et al, 2008; Wolf, 1992) that were all included in the
systematic review by Ernst (2011). The review reported that none of the trials found significant
differences between homeopathy and placebo on any outcome. Cooper and Relton (2010) concluded
that the limited evidence available is flawed due to low sample sizes (as a result of poor recruitment),
high withdrawal rates and poor reporting of results in the Level II studies; however, they did not
provide quality scores for each of the included studies. Based on the available evidence, Cooper and
Relton (2010) found that there is no evidence to suggest a statistically significant effect of
homeopathic medicines for patients with insomnia.
Finally, Linde and Melchart (1998) (AMSTAR score 8/11) conducted an earlier systematic review that
examined the efficacy of homeopathy in a wide range of clinical conditions. The Level II study by
Carlini et al (1987) was the only study of insomnia or other sleep or circadian rhythm disturbances
included in the review. No significant differences were found between the patients who received
individual homeopathic simillimum and those who received placebo; however, the outcomes used to
measure inter-group differences were not clear. More than half of the patients (26/44) dropped out
of the study. As a result, only 18 patients were included in the analysis which draws into question the
reliability of the results.
Prepared for the NHMRC Homeopathy Working Committee by Optum 246
EFFECTIVENESS OF HOMEOPATHY FOR CLINICAL CONDITIONS: OVERVIEW REPORT October 2013
Reviewer comments
Due to the limited evidence base and the heterogeneity of the data set, Davidson et al (2011) decided
that a meta-analysis of the results was not meaningful. The evidence reviewer supports the decision
not to pool results, as the patient populations that were included in the “sleep or circadian rhythm
disturbances” group included patients with insomnia, severe snoring, jet lag, and shift lag in night
shift workers. The homeopathic approach adopted in each of the five Level II trials also varied greatly.
Some statistically significant differences between homeopathy and placebo were achieved for
patients with severe snoring and jet lag; although there was only one trial available for each
condition, with flaws in the methodology and small sample sizes (N=23 and N=44 in jet lag and severe
snoring, respectively).
Evidence statement
Four systematic reviews of medium quality identified eight randomised controlled trials (poor to
medium quality; total of 330 participants, range: 23-96) that compared homeopathy with placebo for
the treatment of people with sleep or circadian rhythm disturbances.
These studies are of insufficient quality and/or size to warrant further consideration of their findings.
LOC: Very low - low.
Based on the body of evidence evaluated in this review there is no reliable evidence that
homeopathy is more effective than placebo for the treatment of people with sleep or circadian
rhythm disturbances.
Table 83 Evidence summary table: the effectiveness of homeopathy for the treatment of sleep or circadian rhythm disturbances
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Ernst (2011) Naude et al (2010) Not reported – Individualised Placebo Sleep diary “Change in total hours of sleep per “In conclusion, the notion
[Level I] [Level II] assumed to be homeopathy week favoured homeopathy” that homeopathic
d patients with for 4 weeks remedies are effective for
AMSTAR: 6/10 Moderate quality
N=30 insomnia or sleep- the treatment of insomnia
SR of related disorders and sleep-related
homeopathy for disorders is not supported
Kolia-Adam et al Not reported – Coffea cruda Placebo Sleep duration No significant difference
insomnia and by the best available
(2008) assumed to be 200C for 1
sleep-related Sleep pattern No significant difference evidence. It is
[Level II] patients with month
disorders d
recommended that future
Poor quality insomnia or sleep-
trials of homeopathy and
N=30 related disorders
insomnia be conducted
using adequate and
La Pine et al (2006) Nurses doing shift No-Shift-Lag Placebo Sleep quality No significant difference
rigorous study designs.
[Level II] work for 1 week
d Fatigue No significant difference Until consistently positive
Moderate quality evidence emerges,
N=34 proponents of
homeopathy should
Cialdella et al Not reported – Homeogene Placebo Clinical Global No significant difference
abstain from making such
(2001) assumed to be or Sedatif PC Impression
therapeutic claims”.
[Level II] patients with for 1 month Improvement
d insomnia or sleep- scale
Poor quality
N=96 related disorders
Wolf (1992) Not reported – Requiesan for Placebo Sleep duration No significant difference
[Level II] assumed to be 1 month
d patients with Sleep quality No significant difference
Poor quality
N=29 insomnia or sleep- Decrease in sleep No significant difference
related disorders latency (baseline;
1 month)
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
reporting
improvement,
night awakenings
Carlini et al (1987) Not reported – Individualised Placebo Sleep duration No significant difference
[Level II] assumed to be homeopathy
d patients with for 45 days Sleep quality No significant difference
Poor quality
N=44 insomnia or sleep- Evaluation by No significant difference
related disorders clinician
Davidson et al Kumar (2010) Patients with jet Combined Placebo POMS-Fatigue Results favour homeopathy (p<0.05). There is mixed evidence
(2011) [Level II] lag multiple Effect size: 0.24. for sleep- and circadian
[Level I] SIGN score: poor remedy rhythm-related problems.
product POMS-Vigor No significant difference between
AMSTAR: 8/10 N=23
treatment arms. Inconsistently
Two studies (Lipman et al
reported p-values; ambiguous, but
SR of 1999; Naude et al, 2010),
results warrant further study.
homeopathy for with relatively high scores
Effect size: 0.17. on GRADE evaluation,
multiple
conditions Naude et al (2010) Patients with Individualised Placebo Sleep diary Benefit for homeopathy (p<0.05). yielded predominantly
[Level II] primary insomnia homeopathy positive results. However
SII Effect size (95% CI): 2.40 (1.46, 3.34). they addressed different
SIGN score: fair
Benefit for homeopathy (p<0.0001). conditions, so the authors
N=16
do not believe that “the
DBAS No significant difference between cumulative evidence for
treatment arms. any one condition
Kolia-Adam (2008) Patients with Coffea cruda Placebo Unclear “Rate of response”: warrants with a positive or
[Level II] insomnia of less 200C Homeopathy – 33%; Placebo – 50%. a negative overall
than 1 year in Significance not reported. recommendation for this
SIGN score: poor
duration group”.
N=15 Sleep duration No significant difference between
treatment groups.
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Effect size (95% CI): 0.24 (-0.53, 1.02). There is positive evidence
that homeopathy is
Sleep No significant difference between
effective in severe snoring.
satisfaction treatment groups.
NNT: -5.99 (placebo was more
effective). “Mainly because of the
limited number of studies
Sleep pattern No significant difference between in any single category and
treatment groups. heterogeneity of the data
set, we decided that meta-
La Pine et al (2006) Night shift workers Combined 5- Placebo CAVT No significant difference between
analysis was not
[Level II] with shift lag remedy treatment groups
meaningful”
SIGN score: poor product
IIQ No significant difference between
N=34 treatment groups Overall, confidence in the
results was graded as
Fatigue Effect size: 0.03 (-0.49, 0.56)
moderate or low,
Lipman et al (1999) Patients with Combined 9- Placebo Snoring daily Statistically significant difference suggesting that further
[Level II] severe snoring remedy score favouring homeopathy. Homeopathy research could well change
SIGN score: fair product group: 80%; Control group: 46%; the estimate of effect”
N=44
e p<0.001
Global rating NNT: 2.95
Cooper and Kolia-Adam (2008) Patients with Formulaic Placebo Increase in sleep Significant improvement compared to The limited evidence
Relton (2010) [Level II] insomnia >1 year homeopathic duration baseline (homeopathy: 38 minutes, available does not indicate
[Level I] Quality not mean age 32- medicine: compared to p=0.003; placebo: 35 minutes, a statistically significant
AMSTAR: 7/10 reported 33 years Coffea cruda baseline p=0.007). No significant inter-group effect of homeopathic
N=30 200C differences were reported medicines for insomnia
SR of treatment.
Improvement in Both groups experienced a significant
homeopathy for sleep pattern improvement from baseline. No inter-
insomnia Two studies reported a
group differences reported
trend towards better
Cialdella et al Patients with Formulaic Placebo Proportion of No significant intergroup differences. outcomes in the
(2001) insomnia homeopathic patients Homeogene-46: 10/15 (67%); Sedatif- homeopathy group,
receiving low-dose medicines: completing the PC: 12/20 (60%); Placebo 13/36 (50%) however the differences
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
[Level II] benzodiazepines for Homeogene- study and were non-significant.
≥3 months prior to f
Quality not 46 or Sedatif- showing
baseline PC
g
improvement or
reported Major flaws existed in the
mean age 54 years
N=96 no change in Level II studies in terms of
symptoms at 1 concealment of allocation,
month accrual of participants to
sufficiently power the
studies, and reporting of
statistical differences (e.g.
in one studies it was
unclear whether the p-
Proportion of Homeopathy groups: values referred to
patients (i) 33% (ii) 30% (iii) 37% differences between
preferring: groups or from baseline, in
(i) study Placebo group: another the p-values were
treatment (i) 19% (ii) 38% (iii) 43% misinterpreted).
(ii) prior BZD
treatment All four Level II studies
(iii) no involved small patient
treatment/other numbers, with the largest
treatment/no study reporting a lack of
preference statistical power due to
accrual difficulties. The
Number of No significant difference between
included Level II studies
patients patients in the homeopathy compared
were poorly reported with
requesting a to placebo groups
high patient withdrawal
return to BZD
rates.
treatment
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Wolf (1992) Patients with Formulaic Placebo Percentage of No significant difference between
[Level II] difficulty falling homeopathic patients groups, although a higher proportion
Quality not asleep or staying medicine: reporting of patients in the homeopathy group
h
reported asleep Requiesan improvement reported improvement (n=8/14; 57%)
N=29 aged 19 to 73 compared to the placebo group
years (n=4/14; 29%)
Carlini et al (1987) Patients with Individualised Placebo Sleep duration Both groups experienced significant
[Level II] severe insomnia homeopathic improvement from baseline to Day 15
medicine and at all timepoints until 3 months.
Study ID Included study Patient Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of population systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Quality not (agreed by 2 No significant difference between
reported homeopaths) patients starting on intervention or
N=44 placebo
Linde and Carlini et al (1987) Patients with Individual Placebo Unclear No difference between groups The authors did not
Melchart (1998) [Level II] insomnia simillimum in provide an overall
i potencies C6 conclusion regarding the
[Level I] Quality:3, 4.5
AMSTAR: 8/11 N=44 to C200 efficacy of homeopathy in
insomnia; however they
SR of did state that the trial had
homeopathy for an “extremely high drop-
multiple out (rate)”.
conditions
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; C, centesimal; CAVT, Computer-Assisted Vigilance Test; DBAS, Dysfunctional Beliefs About Sleep; IIQ, Impact of
Intervention Questionnaire; NNT, number needed to treat; POMS, Profile of Mood States scale; SIGN, Scottish Intercollegiate Guidelines Network; SII, Severity of Insomnia Index; SR, systematic
review.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
d
Risk of bias was assessed using the Cochrane criteria
e
Number of participants who completed evaluation. Total number randomised not reported.
f
Contains Stramonium 3DH, Hyoscyamus niger 3DH, Passiflora incarnata 3DH, Ballota foetida 3DH and Nux moschata 4CH.
g
Contains Aconitum napellus 6CH, Belladonna 6CH, Calendula officinalis 6CH, Abrus precatorius 6CH, Chelidonium majus 6CH and Viburnum opulus 6CH.
h
Contains two herbal medicines: California sleep poppy (Radix Eschscholzia californica) and green oats (Avena sativa), and two homeopathic medicines: Coffea D3 and Arnica D3.
i
Quality was assessed according to (i) Jadad score (out of five); (ii) internal validity score (out of six).
Evidence statement
One systematic review of good quality identified one very small randomised controlled trial (poor
quality; 29 participants) that compared homeopathy (Arnica) with placebo for the treatment of the
adverse effects of venous cannulation in people undergoing chemotherapy. LOC: Very low.
Based on only one very small poor quality study there is no reliable evidence on which to draw a
conclusion about the effectiveness of homeopathy compared to placebo for the treatment of the
adverse effects of venous cannulation in people undergoing chemotherapy.
Table 84 Evidence summary table: the effectiveness of homeopathy for the treatment of adverse effects of venous cannulation
Study ID Included Patient population Intervention Comparator Outcome Results as reported in the Systematic review
Level of study systematic review interpretation
a
evidence Level of
b a
Quality evidence
c
Quality
Sample size
Kassab et al Bourgois Women with breast cancer Homepathic Arnica 5C – Placebo – 3 Improvements No significant inter-group In general there were
(2011) (1984) mean age (SD): 54.41 years (7.61 three granules 4 times a granules 4 from baseline differences mixed findings or
[Level I] [Level II] years) day for 3 days before times a day for assessed by: unclear risk of bias.
AMSTAR: High risk of receiving chemotherapy and 3 days after 3 days before pain produced by the
d suffering adverse effects of venous treatment, for 2 and 3 days after injection or
9/10 bias Overall the authors
cannulation chemotherapy cycles treatment, for haematoma(s)
N=29 concluded that there is
previously responded to Arnica in an venous tone
SR of 2 chemo- no evidence to support
open-label trial assessed by the no.
homeopathy therapy cycles the efficacy of
of haematomas
for adverse venous accessibility homeopathic
effects of assessed by the no. medicines for adverse
cancer of attempts at effects of cancer
treatments cannulation treatments (other than
preliminary data to
support the use of
Traumeel S
mouthwash in the
treatment of
chemotherapy-induced
stomatitis).
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; C, centesimal; NR, not reported; SR, systematic review.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
d
Quality assessed using the Delphi List and Cochrane Collaboration tool for assessing bias.
Evidence statement
One systematic review (2011) did not identify any prospectively designed and controlled studies that
assessed the effectiveness of homeopathy compared with placebo for the treatment of people with
chemotherapy-associated nausea/vomiting.
One systematic review of good quality identified one small randomised controlled trial (quality
unclear; 65 participants) that compared two homeopathic medicines (Vomitusheel S and
Gastricumeel) with another homeopathic medicine with no claimed antiemetic properties for the
treatment of people with chemotherapy-associated nausea/vomiting. LOC: Very low.
Based on only one small study of unknown quality there is no reliable evidence on which to draw a
conclusion about the effectiveness of homeopathy compared to placebo for the treatment of people
with chemotherapy-associated nausea/vomiting.
Table 85 Evidence summary table: the effectiveness of homeopathy for the treatment of chemotherapy-associated nausea/vomiting
Study ID Included Patient population Intervention Comparator Outcome Results as reported in the Systematic review
Level of study systematic review interpretation
a
evidence Level of
b a
Quality evidence
c
Quality
Sample size
e
Kassab et al Daub et al Women with breast cancer Vomitusheel S given as Sambucus nigra Percentage of No significant difference In general there were
g
(2011) (2005) aged 28-67 years a suppository and D3 oral tablets patients requiring between groups. mixed findings or
f
[Level I] [Level II] undergoing chemotherapy Gastricumeel given as additional Intervention group: unclear risk of bias.
AMSTAR: Unclear risk all participants received standard oral tablets conventional 68.2%; control group:
of bias
d antiemetics on day 1. If nausea or treatment for 59.1% (p=0.6)
9/10 Overall the authors
vomiting occurred on subsequent nausea/vomiting
h
N=65 days, participants received either the
concluded that there is
SR of homeopathic intervention or the no evidence to support
homeopathy comparator. the efficacy of
for adverse homeopathic
effects of medicines for adverse
cancer effects of cancer
treatments treatments (other than
preliminary data to
support the use of
Traumeel S
mouthwash in the
treatment of
chemotherapy-induced
stomatitis).
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; D, decimal; NR, not reported; SR, systematic review.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
d
Quality assessed using the Delphi List and Cochrane Collaboration tool for assessing bias.
e
Vomitushell S is a proprietary complex homeopathic medicine containing Ipecacuanha D2 (1.1mg), Aesthusea D2 (1.1mg), Nux vomica D2 (1.1mg), Apomorphium hydrochloricum D4 (1.65mg),
Colchicum D4 (2.75mg), Ignatia D4 (3.3mg)
f
Gastricumeel is a proprietary complex homeopathic medicine containing Argentum nitricum D6 (30mg), Acidum arsenicosum D6 (30mg), Pulsatilla D4 (60mg), Nux vomica D4 (60mg), Carbo
vegetablis D6 (60mg), Antimonium crudum D6 (60mg)
g
The “placebo” was another homeopathic medicine that the authors chose because “no antiemetic properties had been described”.
h
Additional conventional treatment was given if nausea/vomiting had not resolved within two hours of receipt of intervention or “placebo”.
Table 86 Matrix indicating the studies that were included in the systematic reviews of chemotherapy-induced
stomatitis
Systematic review
Bellavite et al (2011) Kassab et al (2011) Milazzo et al (2006)
[Level I] [Level I] [Level I/III]
Oberbaum et al (2001)
[Level II]
Study ID
Oberbaum (1998)
[Level III-2]
Milazzo et al (2006) (AMSTAR score 7/10) carried out a systematic review that assessed the efficacy
of homeopathic therapy as a sole or additional therapy in cancer care and identified two studies
(Oberbaum, 1998; Oberbaum et al, 2001) that examined homeopathic TraumeelS as a treatment for
chemotherapy-induced stomatitis. The Level III-2 study by Oberbaum (1998) was a pilot, case-control
study conducted in order to inform the later Level II study by Oberbaum et al (2001). Oberbaum
(1998) reported a highly statistically significant reduction in the homeopathy group in terms of the
duration of symptoms, however no numerical evidence was provided to support the findings. The
study received a Jadad score of 0 in the quality assessment by Milazzo et al (2006), and therefore
reliability and validity of the results is questionable.
The Level II study identified by Milazzo et al (2006) (Oberbaum et al, 2001; Jadad score 4) examined
homeopathic TraumeelS in patients aged 3 to 25 that had malignant blood cancer and underwent
allogeneic or autologous stem-cell transplantation. Oberbaum et al (2001) found that the reduction
of severity and/or duration of stomatitis, mean “area under the curve”, and mean time to worsening
of symptoms all significantly favoured homeopathy. Milazzo et al (2006) did not report p-values for a
number of other outcomes, including median time to worsening of symptoms, oral pain and
discomfort, and difficulty to swallow. Overall Milazzo et al (2006) concluded that cancer patients
“appear to have benefited from homeopathic interventions for chemotherapy-induced stomatitis”
and that “encouraging results” in Oberbaum et al (2001) highlighted the need to perform a larger
trial.
Kassab et al (2011) (AMSTAR score 9/10) conducted a Cochrane review that examined the
effectiveness of homeopathy for the treatment of adverse effects of a variety of cancer treatments.
The Level II study by Oberbaum et al (2001) was included in the review, although Kassab et al (2011)
reported fewer outcomes from the trial than Milazzo et al (2006). Overall, Kassab et al (2011) stated
that there was “preliminary data in support of TraumeelS mouthwash in the treatment of
chemotherapy-induced stomatitis” that needs replication to provide any firm conclusions.
Finally, Bellavite et al (2011) (AMSTAR score 5/10) performed a systematic review of the
effectiveness of homeopathy for a variety of clinical conditions, including chemotherapy-associated
stomatitis from one Level II study (Oberbaum et al, 2001). Bellavite only reported the results of two
outcomes (percentage of patients who did not develop stomatitis and mean area under the curve for
Prepared for the NHMRC Homeopathy Working Committee by Optum 259
EFFECTIVENESS OF HOMEOPATHY FOR CLINICAL CONDITIONS: OVERVIEW REPORT October 2013
stomatitis scores), the latter of which was found to significantly favour homeopathy (p<0.01). Based
on the results of the Level II study by Oberbaum et al (2001), Bellavite et al (2011) concluded that
TraumeelS “may reduce the severity and duration of chemotherapy-induced stomatitis in children
undergoing bone marrow transplantation”.
Reviewer comments
The results of the Level II study (Oberbaum et al, 2001) were reported inconsistently between the
three systematic reviews. For example, Bellavite et al (2011) reported “percentage of patients who
did not develop stomatitis” as an outcome, suggesting that the trial was, in fact, examining Traumeel
as a prophylactic intervention. However, the description of the trial in the other two systematic
reviews (Kassab et al, 2011; Milazzo et al, 2006) and the outcomes reported suggested that the trial
examined the treatment of existing stomatitis.
Evidence statement
Three systematic reviews of poor to good quality identified one very small randomised controlled
trial (good quality; 32 participants) and one very small prospectively designed, non-randomised
controlled study (poor quality; 27 participants) that compared homeopathy (Traumeel S) with
placebo for the treatment of people with chemotherapy-induced stomatitis.
These studies are of insufficient quality and/or size to warrant further consideration of their findings.
LOC: Very low.
Based on the body of evidence evaluated in this review there is no reliable evidence that
homeopathy is more effective than placebo for the treatment of people with chemotherapy-induced
stomatitis.
Table 87 Evidence summary table: the effectiveness of homeopathy for the treatment of chemotherapy-induced stomatitis
Study ID Included Patient population Intervention Comparator Outcome Results as reported in Systematic review
Level of study the systematic review interpretation
a
evidence Level of
b a
Quality evidence
c
Quality
Sample
size
Bellavite et Oberbaum Children and young adults with Homeopathic complex Placebo (local Percentage of Significance of results not “These results suggest
al (2011) et al (2001) chemotherapy-associated Traumeel-S therapy with patients who did reported that this homeopathic
[Level I] [Level II] stomatitis who had undergone mouth rinsing) not develop Homeopathy: 33% complex may reduce
AMSTAR: Quality not stem cell transplantation stomatitis Placebo: 7% the severity and
5/10 specified duration of
Mean AUC (severity Significant difference in chemotherapy-induced
N=32 and duration of favour of homeopathy
SR of stomatitis in children
stomatitis) (p<0.01) undergoing bone
homeopathy Homeopathy: 10.4
for multiple marrow
Placebo: 24.3
conditions transplantation”
e
Kassab et al Oberbaum Patients suffering from malignant TraumeelS® – supplied Placebo – Mean AUC (severity Homeopathy group: 10.4; In general there were
(2011) et al (2001) disease who had undergone as 2.2ml ampoules used supplied as and duration of Placebo group: 24.3. mixed findings or
[Level I] [Level II] allogeneic or autologous stem cell as a mouthwash for a 2.2ml ampoules stomatitis) Wilcoxon rank-sum unclear risk of bias.
AMSTAR: Low risk of transplantation minimum of 30 used as a score: 167.5; expected
d
9/10 bias aged 3-25 years seconds, 5 times per mouthwash for score 232.5; p<0.01) There is preliminary
N=32 day, alongside standard a minimum of data to support the
mouthcare 30 seconds, 5 Time to worsening Log-rank test indicated a
SR of efficacy of Traumeel S
times per day, of symptoms statistically significant
homeopathy mouthwash in the
alongside difference between the
for adverse treatment of
standard two groups (chi-square
effects of chemotherapy-induced
mouthcare test, 13.4 with 1 degree
cancer stomatitis, but there is
of freedom; p<0.001)
treatments no evidence to support
Median time to Homeopathy group: 4.7 the efficacy of
worsening in those days; Placebo group: 4.0 homeopathic
patients whose days. Significance NR. medicines for other
symptoms adverse effects of
worsened cancer treatments.
Study ID Included Patient population Intervention Comparator Outcome Results as reported in Systematic review
Level of study the systematic review interpretation
a
evidence Level of
b a
Quality evidence
c
Quality
Sample
size
Patient-reported Reduction in all three
score symptoms (pain, dryness,
dysphagia) in Traumeel
group compared to
placebo (p=NR).
g
Milazzo et al Oberbaum Patients with blood malignant TraumeelS® Placebo Mean AUC (severity Statistically significant “Cancer patients
(2006) et al (2001) cancer who underwent allogeneic and duration of difference between appear to have
[Level I/III] [Level II] or autologous stem-cell stomatitis) groups. Homeopathy: benefited from
AMSTAR: Jadad score transplantation 10.4; Placebo: 24.3; homeopathic
7/10 4
f aged 3-25 years p<0.01 interventions
N=30 specifically for
Mean time to Statistically significant chemotherapy-induced
SR of worsening of difference between
homeopathy stomatitis”.
symptoms groups favouring
for cancer homeopathy.
treatment “The evidence
Homeopathy group: 6.9
emerging from this
days; placebo group: 4.3
systematic review is
days; p<0.001
encouraging but not
Median time to Homeopathy group: 4.7 convincing. Further
worsening in those days; placebo group: 4.0 research should
patients whose days. p-value not attempt to answer the
symptoms specified many open questions
worsened related to
homeopathy”.
Severity score Significant difference
(subgroup analysis between treatment
of patients aged groups favouring
less than 15 years) homeopathy.
Homeopathy group: 11;
placebo group: 25.9;
p<0.01
Study ID Included Patient population Intervention Comparator Outcome Results as reported in Systematic review
Level of study the systematic review interpretation
a
evidence Level of
b a
Quality evidence
c
Quality
Sample
size
Oral pain and Patients in the
discomfort intervention group
experienced a reduction
(no p-values provided)
Study ID Included Patient population Intervention Comparator Outcome Results as reported in Systematic review
Level of study the systematic review interpretation
a
evidence Level of
b a
Quality evidence
c
Quality
Sample
size
Jadad score similar stages Use of opiates Non-significant trend
f
0 of cancer, who suggesting less patients
N=27 received no in the intervention group
treatments for required opiates
stomatitis compared to the control
group (p=0.09)
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; AUC, area under the curve; NR, not reported; SR, systematic review.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
d
Quality assessed using the Delphi List and Cochrane Collaboration tool for assessing bias.
e
TraumeelS is a proprietary complex homeopathic medicine. Each 2.2ml ampoule contains: Arnica montana D2 (2.2mg), calendula officianalis D2 (2.2mg), Achillea millefolium D3 (2.2mg),
Matricharia chamomilla D2 (2.2mg), Symphytum officinale D6 (2.2mg), Atropa belladonna D2 (2.2mg), Aconitum napelus D2 (1.32mg), Bellis perenis D2 (1.1mg), Hypericum perfoliatum D2
(0.66mg), Echinacea angustifolia D2 (2.2mg), Echinacea purpurea D2 (2.2mg), Hammamelis virginica D1 (0.22mg), Mercurius solubilis D1 (1.1mg), and Hepar sulphuris D6 (2.2mg).
f
The Jadad scale assesses the quality of published clinical trials based methods relevant to random assignment, double blinding and the flow of patients. The range of possible scores is zero
(bad quality) to 5 (good quality).
g
Traumeel® is a homeopathic preparation containing: arnica 2X, calendula 2X, millefolium 3X, chamomilla 3X, symphytum 6X, belladonna 2X ana 0.1ml, aconitum 2X 0.06ml, bellis perennis 2X
0.05ml, hypericum 2X 0.03ml, echinacea angustifolia 2X, echniacea purpurea 2X ana 0.025ml, hamamelis 1X 0.01, mercurius sol. 6X 0.05g, and hepar sulfuris 6X 0.1g.
Table 88 Matrix indicating the studies that were included in the systematic reviews of hot flushes
Systematic review
Kassab et al (2011) Milazzo et al (2006) Rada et al (2010)
[Level I] [Level I/III] [Level I]
Jacobs et al (2005)
[Level II]
Study ID
Thompson et al (2005)
[Level II]
Rada et al (2010) (AMSTAR score 8/10) conducted a Cochrane review that aimed to assess the
efficacy of non-hormonal therapies for reducing hot flushes in women with a history of breast
cancer. The authors identified two Level II studies (Jacobs et al, 2005; Thompson et al, 2005) that
compared homeopathy with placebo. Rada et al (2010) assessed the risk of bias in the included
studies using the criteria established in the Cochrane Handbook for Systematic Reviews of
Interventions. No overall quality ratings were provided, however, both of the studies scored well
according to the majority of the quality criteria, indicating a low overall risk of bias. Jacobs et al
(2005) was a Level II study that compared two forms of homeopathy (single or combination therapy)
with placebo in women with a history of breast cancer and at least three episodes of hot flushes per
day for at least one month. There were no statistically significant differences among comparisons for
the frequency or severity score of hot flushes. There was, however, a significant improvement in
quality of life scores in women who used single or combination homeopathy (p-value not reported).
Thompson et al (2005) examined the effect of a tailored homeopathic prescription or placebo in
women with non-metastatic breast cancer who experienced more than three hot flushes per day.
The study reported that no significant effects were observed in a four-item profile score that
included two self-rated symptom items, an activity of daily living item and a general feeling of well-
being item (mean difference -0.10; 95% CI -4.86, 4.66).
Rada et al (2010) noted that the major limitation of the two included studies was loss to follow up.
The authors concluded that “the available evidence suggests that homeopathy provides no
significant benefit compared to placebo” and “even though the studies had limited power to show an
effect, none of them showed significant benefit or supported the use of homeopathy”.
Kassab et al (2011) (AMSTAR score 9/10) conducted a Cochrane review that focused specifically on
homeopathy for the treatment of adverse effects of cancer treatments. The same two studies
included in Rada et al (2010) (Jacobs et al, 2005; Thompson et al, 2005). The studies were both
assessed to be of “high quality and low risk of bias” by Kassab et al (2011). Kassab et al (2011)
reported that the primary outcome investigated by Jacobs et al (2005) was hot flush severity score,
which was not associated with a significant difference between the intervention group (single and
combination homeopathic remedies) and placebo. However a post hoc, subgroup analysis indicated
that patients not receiving tamoxifen that were randomised to combination homeopathic medicine
(Hyland’s menopause) had significantly higher hot flush severity scores and total number of hot
flushes than the single remedy and placebo groups. Thompson et al (2005) was reported as finding
no statistically significant differences between individualised homeopathy and placebo, based on
symptom and mood disturbances or other self-reported outcomes. Overall, Kassab et al (2011)
concluded that there was “no convincing evidence” for the efficacy of homeopathy in the treatment
of hot flushes in women with a history of breast cancer.
Finally, Milazzo et al (2006) (AMSTAR score 7/10) carried out a systematic review that assessed the
efficacy of homeopathic therapy in cancer treatment. The authors identified the same two Level II
studies (Jacobs et al, 2005; Thompson et al, 2005), and gave them both Jadad scores of 5. Milazzo et
al (2006) reported that the study by Jacobs et al (2005) found that homeopathy resulted in an
improvement in general health score compared with placebo (p<0.03 and p=0.02 in the combination
and single remedies, respectively). In addition, Jacobs et al (2005) was reported to have found that
the whole combination therapy group had statistically significantly higher rates of headaches than
those in the other treatment arms (p=0.03). Consistent with the other systematic reviews, Milazzo et
al (2006) reported that Thompson et al (2005) found no statistically significant differences between
individualised homeopathy and placebo. Milazzo et al (2006) stated that even though the trials
received a Jadad score of 5 they were not devoid of flaws, particularly small sample sizes that
precluded definitive conclusions. Overall, the Milazzo et al (2006) concluded that there is
“insufficient evidence to support clinical efficacy” of homeopathy in cancer care.
Reviewer comments
There was substantial heterogeneity between the trials, particularly in terms of the homeopathic
remedies prescribed. Thirty five different homeopathic medicines were prescribed in Jacobs et al
(2005) and 71 different homeopathic medicines were prescribed in Thompson et al (2005). Only two
of the five most commonly prescribed remedies were common to both studies. The trials by Jacobs et
al (2005) and Thompson et al (2005) also adopted considerably different primary outcomes;
menopausal symptoms and a patient-reported outcome (Measure Your Medical Outcome Profile),
respectively.
Evidence statement
Three systematic reviews of medium to good quality identified two randomised controlled trials
(good quality; 53 and 83 participants) that compared homeopathy with placebo for the treatment of
hot flushes in women with a history of breast cancer.
These studies are of insufficient size to warrant further consideration of their findings. LOC: Low.
Based on the body of evidence evaluated in this review there is no reliable evidence that
homeopathy is more effective than placebo for the treatment of hot flushes in women with a history
of breast cancer.
Table 89 Evidence summary table: the effectiveness of homeopathy for the treatment of hot flushes in women with a history of breast cancer
Study ID Included Patient population Intervention Comparator Outcome Results as reported in the Systematic review
Level of study systematic review interpretation
a
evidence Level of
b a
Quality evidence
c
Quality
Sample size
Kassab et al Jacobs et al Women with a history of Individualised Placebo Hot flush severity Positive trend towards an In general there were
(2011) (2005) carcinoma in situ or Stage homeopathy – score improvement in the single mixed findings or
[Level I] [Level II] I to III breast cancer unrestricted remedy remedy group during the first unclear risk of bias.
AMSTAR: 9/10 Low risk of who had completed all choice and three months of the study,
d surgery, chemotherapy and unrestricted ability
bias however the trend was not Overall the authors
N=83 radiotherapy to change remedy significant (p=0.1) concluded that there is
SR of with hot flushes for at least (single medicine
homeopathy no evidence to support
one month, with an given once monthly General health score Statistically significant
for adverse average of at least three the efficacy of
or bimonthly); or (SF-36) at 1 year improvement in both
effects of hot flushes per day in the homeopathic
Hyland’s homeopathy groups (p<0.05)
cancer week prior to beginning e
medicines for adverse
treatments treatment Menopause (given General health score Significantly increase in both effects of cancer
mean age: 55.5 years 3 times a day) (SF-36) compared with homeopathy groups treatments (other than
placebo compared with placebo preliminary data to
(p=NR) support the use of
Traumeel S
Hot flush severity Highly statistically significant mouthwash in the
score (post hoc increase in the combination treatment of
subgroup analysis homeopathic group chemotherapy-induced
defined by use of (subgroup of patients not stomatitis).
tamoxifen) receiving tamoxifen)
Thompson et al Women treated for Individualised Placebo Symptoms and mood Clinically relevant
(2005) breast cancer homeopathy – disturbances improvements for both
[Level II] more than three hot unrestricted remedy groups. Inter-group
Low risk of flushes per day choice and differences not reported
bias
d no metastatic disease unrestricted ability
not on any other treatment to change remedy MYMOP activity score No evidence of a difference
N=53
for hot flushes between groups (adjusted
not undergoing, or about difference: -0.4,
the receive, any adjuvant 95% CI -0.9, 0.1, p=0.13)
chemotherapy
mean age: 52.7 years
Study ID Included Patient population Intervention Comparator Outcome Results as reported in the Systematic review
Level of study systematic review interpretation
a
evidence Level of
b a
Quality evidence
c
Quality
Sample size
Rada et al Jacobs (2005) Women (mean age 55.5 Single or Placebo SF-36 Significant improvement in The available evidence
(2010) [Level II] years) with a history of combination QoL scores in women using suggests that
[Level I] Quality not breast cancer (carcinoma (Hyland’s single or combination homeopathy provides
AMSTAR: 8/10 specified in situ and stages I to III) menopause) homeopathy (p=NR) no significant benefit
N=83 at least 3 episodes of hot homeopathic compared to placebo
flushes per day for at least remedies Total number of hot No significant difference
SR of CAM for flushes
one month Even though the
hot flushes 58% on tamoxifen
Hot flush severity No significant difference studies had limited
65% taking unspecified
hormones score power to show an
effect, none of them
Kupperman No significant difference reported significant
Menopausal Index benefit or supported
the use of homeopathy
Thompson Women (mean age 52 Individualised Placebo MYMOP activity score No significant difference
(2005) years) with non- homeopathy Mean difference: -0.10 (95%
[Level II] metastatic breast cancer CI -4.86, 4.66)
Quality not more than 3 hot flushes per
specified day Daily living disruption No significant difference
N=53 80% on tamoxifen and general well-being
baseline hot flush
frequency of 7.5 per day Frequency and severity No significant difference
of hot flushes
Study ID Included Patient population Intervention Comparator Outcome Results as reported in the Systematic review
Level of study systematic review interpretation
a
evidence Level of
b a
Quality evidence
c
Quality
Sample size
Milazzo et al Jacobs et al Breast cancer survivors Verum single Placebo General health score Significant improvement in There is insufficient
g
(2006) (2005) remedy plus (SF-36) compared with both homeopathy groups evidence to support
[Level I] [Level II] placebo, or a verum placebo compared to placebo clinical efficacy of
f combination (p<0.03, combination; homeopathic therapy
AMSTAR: 7/10 Jadad score 5
N=83 medicine (Hyland’s p=0.02, single) in cancer care.
h
SR of menopause) plus a
verum single Hot flush severity Statistically significantly
homeopathy score (subgroup not higher in combination group
for cancer remedy
receiving tamoxifen) than single remedy (p<0.001;
treatment 95% CI -51.9, 15.0).
Statistically significantly
higher in combination
homeopathy group than
placebo (p=0.01; 95% CI 6.2,
47.1)
Thompson et al Breast cancer survivors 71 different Placebo MYMOP activity score No significant difference
(2005) with oestrogen remedies (tablets, between treatment groups
withdrawal symptoms liquid, or granules) (p=0.17; 95% CI -1.0, 0.2)
Study ID Included Patient population Intervention Comparator Outcome Results as reported in the Systematic review
Level of study systematic review interpretation
a
evidence Level of
b a
Quality evidence
c
Quality
Sample size
[Level II] no more than three hot MYMOP overall profile No significant difference
f flushes per day
Jadad score 5 score between treatment groups
without metastatic disease (p=0.13; 95% CI -0.9, 0.1)
N=53
no concurrent treatment
for hot flushes
not undergoing
chemotherapy
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; CAM, complementary and alternative medicines; CI, confidence interval; EORTC QLQ-C30, European Organization for
Research and Treatment of Cancer Quality of Life Questionnaire; HADS, Hospital Anxiety and Depression Scale; MYMOP, Measure Your Medical Outcome Profile; NR, not reported; QoL, quality
of life; SF-36, Short Form-36; SR, systematic review.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
d
Quality assessed using the Delphi List and Cochrane Collaboration tool for assessing bias.
e
Hyland’s Menopause is a proprietary combination homeopathic medicine of Amyl Nitrate 3x, Sanguinaria Canadensis 3x and Lachesis 12x.
f
The Jadad scale assesses the quality of published clinical trials based methods relevant to random assignment, double blinding and the flow of patients. The range of possible scores is zero
(bad quality) to 5 (good quality).
g
Single remedies consist of 35 different homeopathic medications, mainly: sepia, calcarea carbonica, sulphur, lachesis, and kali carbinicum
h
Hyland’s menopause contains: amyl nitrate, sanguinaria canadensis, and lachesis
Evidence statement
Three systematic reviews of medium to good quality identified one small randomised controlled trial
(medium quality; 66 participants) that compared homeopathy (Belladona) with placebo for the
treatment of radiodermatitis in women with breast cancer undergoing radiotherapy. LOC: Very low -
low.
Based on only one small study there is no reliable evidence on which to draw a conclusion about the
effectiveness of homeopathy compared to placebo for the treatment of radiodermatitis in women
with breast cancer undergoing radiotherapy.
Table 90 Evidence summary table: the effectiveness of homeopathy for the treatment of radiodermatitis in patients undergoing radiotherapy
Study ID Included Patient population Intervention Comparator Outcome Results as reported in Systematic review
Level of study the systematic review interpretation
a
evidence Level of
b a
Quality evidence
c
Quality
Sample
size
Simonart et Balzarini et Breast cancer patients aged 28-70 Belladona 7 cH and X- Placebo Breast skin colour No significant difference “The hypothesis that
al (2011) al (2000) years with radiodermatitis and ray 15 cH for 10 weeks score any dermatological
[Level I] [Level II] who are undergoing radiotherapy condition responds
AMSTAR: Quality not convincingly better to
Warmth score No significant difference homeopathic
8/10 specified
N=66 treatment than to
SR of placebo or other
homeopathy control interventions is
Swelling score No significant difference
for multiple not supported by
conditions evidence”.
Kassab et al Balzarini et Women who had undergone Belladonna 7cH – three Placebo Total severity of No significant difference In general there were
(2011) al (2000) conservative surgery for breast granules twice daily and skin reactions between groups mixed findings or
[Level I] [Level II] cancer and were being treated X-ray 15cH three during radiotherapy unclear risk of bias.
AMSTAR: Unclear risk with radiotherapy granules once daily (based on skin
d
9/10 of bias mean age: 52.7 years, range: 28.3 to colour, heat to There is preliminary
N=66 70 years touch, data to support the
SR of hyperpigmentation efficacy of Traumeel S
homeopathy and oedema) mouthwash in the
for adverse treatment of
Study ID Included Patient population Intervention Comparator Outcome Results as reported in Systematic review
Level of study the systematic review interpretation
a
evidence Level of
b a
Quality evidence
c
Quality
Sample
size
effects of Total severity of Statistically significant chemotherapy-induced
cancer skin reactions reduction in stomatitis, but there is
treatments during recovery homeopathy-treated no evidence to support
(based on skin patients (p=0.05) the efficacy of
colour, heat to homeopathic
touch, oedema and medicines for other
hyperpigmentation) adverse effects of
cancer treatments.
Milazzo et al Balzarini et Breast cancer patients undergoing Belladonna 7cH (three Placebo Hyperpigmentation Significantly less There is insufficient
(2006) al (2000) radiotherapy granules, twice a day) hyperpigmentation in the evidence to support
[Level I/III] [Level II] and X-ray 15cH (once a homeopathy group at clinical efficacy of
AMSTAR: Jadad score day) Week 5 (p=0.050); the homeopathic therapy
e difference was no longer in cancer care.
7/10 4
N=61 statistically significant by
SR of the end of the 10-week
homeopathy follow-up (p=0.060)
for cancer Skin heat Significant decrease in
treatment the homeopathy group
compared to placebo at
Week 8 (p=0.011).
However the benefit was
transient as the
difference was no longer
significant at the 10-
week follow-up (p=0.250)
Study ID Included Patient population Intervention Comparator Outcome Results as reported in Systematic review
Level of study the systematic review interpretation
a
evidence Level of
b a
Quality evidence
c
Quality
Sample
size
recovery. Statistically
significant in recovery
only (p=0.05)
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; cH, Hahnemannian centesimal scale; NR, not reported; SR, systematic review.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
d
Quality assessed using the Delphi List and Cochrane Collaboration tool for assessing bias.
e
The Jadad scale assesses the quality of published clinical trials based methods relevant to random assignment, double blinding and the flow of patients. The range of possible scores is zero
(bad quality) to 5 (good quality).
4.18 Pain
4.18.1 Chronic facial pain
The effectiveness of homeopathy for the treatment of patients with chronic facial pain was assessed
in one systematic review (Myers et al, 2002). Myers et al (2002) (AMSTAR score 3/5) was a
systematic review of complementary and alternative medicines used to treat chronic facial pain,
which failed to identify any Level II studies that tested the effects of homeopathy.
Evidence statement
One systematic review (2002) did not identify any prospectively designed and controlled studies that
assessed the effectiveness of homeopathy in people with chronic facial pain.
Reviewer comments
Although Quinn et al (2006) indicated that the study by Stam et al (2001) was of high methodological
quality, the effectiveness of the comparator (capsicum-based product, Cremor Capsici Compositus) is
unclear and thus the finding of “equal effectiveness” should be interpreted with caution.
Consequently, it is difficult to draw a conclusion about the effectiveness of homeopathy for lower
back pain without a randomised, placebo-controlled trial.
Evidence statement
One systematic review (2006) did not identify any prospectively designed and controlled studies that
assessed the effectiveness of homeopathy compared with placebo for the treatment of people with
lower back pain.
One systematic review of poor quality identified one medium-sized randomised controlled trial (good
quality; 161 participants) that compared homeopathy (Spiroflor SRL) with Cremor Capsici Compositus
for the treatment of people with lower back pain.
This study did not detect a difference between homeopathy and Cremor Capsici Compositus in the
treatment of people with lower back pain and concluded that the products were equally effective.
LOC: Low - moderate.
Based on one medium-sized good quality study there is some evidence that homeopathy is as
effective as Cremor Capsici Compositus (a capsicum based product) for the treatment of people with
lower back pain.
However, the effectiveness of Cremor Capsici Compositus for the treatment of people with lower
back pain is unclear, and it is likely that the study was not sufficiently large to demonstrate ‘equal
effectiveness’. In addition, no placebo controlled studies were identified. Further, the findings of this
study have not been confirmed by other good quality, sufficiently sized studies.
Based on the body of evidence evaluated in this review there is no reliable evidence on which to
draw a conclusion about the effectiveness of homeopathy for the treatment of people with lower
back pain.
Table 91 Evidence summary table: the effectiveness of homeopathy for the treatment of lower back pain
Study ID Included study Patient population Intervention Comparator Outcome Results as reported in Systematic review
Level of Level of the systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Quinn et al Stam et al (2001) Not reported. Assumed Homeopathic gel (Spiroflor Standard VAS for pain “Both products equally “While RCTs for
(2006) [Level II] to be patients with SRL) Capsicum- effective but homeopathic those therapies
d lower back pain based Paracetamol use gel had less adverse effects”. which were
[Level I] Quality: high
AMSTAR: 5/10 N=161 product Sleep investigated
(Cremor disturbance produced
SR of CAM for Capsici encouraging results,
pain Compositus) Absence from including yoga,
work homeopathy, herbal
therapies, and
Patient and hypnotherapy, small
general sample sizes and the
practitioner low number of trials
satisfaction investigating
Presence of individual therapies
adverse effects prevents definite
conclusions being
drawn.”
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; CAM, complementary and alternative medicines; SR, systematic review; SRL, undefined. This is the name of the
homeopathic gel; VAS, visual analogue scale.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
d
Study quality as assessed using the van Tulder methodological quality criterion.
Table 92 Matrix indicating the studies that were included in the systematic reviews of pain in dental practice
Systematic review
Raak et al (2012) Linde and Melchart (1998)
[Level I] [Level I]
Sardella (2008)
[Level II]
Rafai (2004)
[Level II]
Study ID
Lökken et al (1995)
[Level II]
Albertini (1984)
[Level II]
Bendre (1980)
[Level II]
Raak et al (2012) (AMSTAR score of 7/11) performed a systematic review of the literature on the use
of homeopathic Hypericum perforatum (St John’s Wort) for pain conditions in dental practice. The
results of five Level II studies were included in their analysis, many of which examined the use of
Hypericum perforatum in combination with homeopathic Arnica. Three studies were rated as weak in
quality (Albertini, 1984; Bendre, 1980; Lökken et al, 1995), one was rated as strong in quality (Rafai,
2004) and the quality of one Level II study was not specified (Sardella, 2008). Raak et al (2012) noted
that a major limitation of the included studies was that they were “highly likely” to be confounded,
mostly by the use of Arnica.
Sardella (2008) was a Level II study that examined the effect of homeopathic Hypericum perforatum
in patients with burning mouth syndrome. The study reported no significant difference in pain relief
between the homeopathy and placebo groups; however, the number of sites with reported burning
sensation was “reduced significantly”. It was unclear from the systematic review whether the
reduction referred to a significant difference in the homeopathy group compared to placebo or
baseline. Rafai (2004) was a study of homeopathic Hypericum perforatum with Arnica in patients
with trismus and postoperative pain after third molar surgery. Lökken et al (1995) examined the
effect of homeopathic treatment (homeopathic Hypericum perforatum with Arnica) in patients with
postoperative pain and other inflammatory events after bilateral oral surgery. Neither of the Level II
studies reported a significant difference between homeopathy and placebo for any of the primary
outcomes. Lökken et al (1995) noted, however, that treatment “tended to improve ability to open
mouth”. Albertini (1984) reported “significant improvements (in pain reduction) after Day 2” in
patients with dental neuropathic pain. Similarly, Bendre (1980) observed that 93% of patients with
pain following tooth extraction showed significant improvements in pain relief and swelling after 48
hours. In both Level II studies, it was unclear if the significant effect was in favour of homeopathic
Hypericum perforatum and Arnica or placebo.
Raak et al (2012) conducted a meta-analysis of the results from four of the included Level II studies
(Albertini, 1984; Bendre, 1980; Lökken et al, 1995; Rafai, 2004). The study found no statistically
significant difference in dental pain between homeopathic Hypericum perforatum and placebo, but
the effect slightly favoured homeopathy (RR 0.24; 95% CI 0.06, 1.03). The authors also noted that the
meta-analysis was highly heterogeneous (I2=0.89). Importantly, at the time of the systematic review
there were no properly conducted Level II studies that had tested the effect of Hypericum
perforatum alone. In addition to the studies discussed above, Raak et al (2012) examined case
reports that suggested a therapeutic effect of Hypericum perforatum; however, the results were
usually confounded by Arnica. Overall, the authors concluded that “evidence from RCTs does not
support the use of Hypericum perforatum alone, for pain conditions in dental care”. In addition, “the
use of Hypericum perforatum is currently not adequately supported by properly conducted clinical
trials with Hypericum perforatum alone”.
Linde and Melchart (1998) (AMSTAR score 8/11) also conducted a systematic review of the efficacy
of individualised homeopathy across a range of clinical conditions, including pain after oral surgery.
The same Level II study by Lökken et al (1995) was identified that compared treatment preference,
pain, swelling and bleeding in patients treated with homeopathy and placebo in a cross-over design.
Although swelling favoured homeopathy, treatment preference favoured placebo. None of the
differences were reported to be statistically significant. Linde and Melchart (1998) stated that the
trial was rigorous in terms of methodology; however, it was thought to have an “artificial study
model” due to an unusually high frequency of remedy application. Overall, the authors of the
systematic review concluded that, across all clinical conditions, any evidence suggesting that
homeopathy has an effect over placebo is “not convincing because of methodological shortcomings
and inconsistencies”.
Evidence statement
Two systematic reviews of medium quality identified five randomised controlled trials (poor to good
quality; total of 364 participants, range: 24-200) that compared homeopathy with placebo for the
treatment of people with pain in dental practice. LOC: Very low - low.
Based on the body of evidence evaluated in this review homeopathy is not more effective than
placebo for the treatment of people with pain in dental practice.
Table 93 Evidence summary table: the effectiveness of homeopathy for the treatment of pain in dental practice
Study ID Included study Patient population Intervention Comparator Outcome Results as reported in Systematic review
Level of Level of the systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Raak et al Sardella (2008) Patients with burning 300mg capsules containing Placebo Pain relief No significant results “The use of
(2012) [Level II] mouth syndrome H. perforatum extract Hypericum
(hypericin 0.31% and Number of sites “Reduced significantly” perforatum is
[Level I] Quality not
hyperforin 3.0%) three with reported (unclear whether vs placebo currently not
AMSTAR: 7/11 specified
times a day for 12 weeks burning or baseline) adequately
N=39 sensation
SR of supported by
homeopathy Rafai (2004) Patients with trismus 3+3 globuli of Placebo Reduction of No significant results properly conducted
for pain [Level II] and postoperative pain Arnica/Hypericum D30 trismus clinical trials with
after third molar before surgery and Hypericum
Quality: strong
surgery continued for 5 Pain relief No significant results perforatum alone”
N=41
postoperative days
Albertini (1984) Patients with dental 4+4 granula of Placebo Pain reduction “Significant improvements
[Level II] neuropathic pain Arnica/Hypericum directly after Day 2”
Quality: weak after the visit and for 2
N=60 days
Bendre (1980) Patients with post 4 globuli of Placebo Pain relief and “93% of patients showed
[Level II] extraction pain and Arnica/Hypericum directly swelling (not significant improvements in
Quality: weak swelling after tooth extraction and reported pain relief and swelling after
N=200 15 minutes later separately) 48 hours”
Linde and Lökken et al Patients with pain after Best-fitting simillimum Placebo Treatment “No significant differences”. “Rigorous trial;
Study ID Included study Patient population Intervention Comparator Outcome Results as reported in Systematic review
Level of Level of the systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
d
Melchart (1995) oral surgery (83% from 6 predefined preference 11 patients preferred uncommonly high
(1998) [Level II] female; age 19 to 28 remedies in D30 given (cross-over homeopathy; 13 preferred frequency of remedy
e years) according to a fixed design) placebo. application; rather
[Level I] Quality: 5, 5.5
AMSTAR: 8/11 N=24 scheme (highly repetitive) Rate ratio (95% CI): 0.85 artificial study
(0.48, 1.50) model”
SR of Pain “Pain similar in both groups”
homeopathy
for multiple Bleeding “Bleeding similar in both
conditions groups”
Evidence statement
One systematic review of medium quality identified three randomised controlled trials (good quality;
total of 181 participants, range: 37-82) that compared homeopathy (Arnica) with placebo for the
treatment of people with pain following orthopaedic surgery. LOC: Low.
Based on the body of evidence evaluated in this review homeopathy is not more effective than
placebo for the treatment of people with pain following orthopaedic surgery.
Table 94 Evidence summary table: the effectiveness of homeopathy for the treatment of pain following orthopaedic surgery
Study ID Included study Patient population Intervention Comparator Outcome Results as reported in the Systematic review
Level of Level of systematic review interpretation
a a
evidence evidence
b c
Quality Quality
Sample size
Roberts et al Brinkhaus et al Patients undergoing Homeopathic Arnica Placebo Pain reduction No difference between the “Homeopathy is not
(2012) (2006) knee procedures following knee surgery intervention and placebo an effective analgesic
[Level I] [Level II] (cruciate ligament, or (cruciate ligament repair or groups modality”
d knee arthroscopy) knee arthroplasty)
AMSTAR: 7/10 Quality: 5/5
N=82
SR of CAM for
Stevinson et al Patients undergoing Arnica 30C or Arnica 6C Placebo Pain reduction No significant differences
pain
(2003) carpal tunnel release following elective carpal between intervention and
[Level II] procedures tunnel surgery, three times placebo groups, although
d per day placebo group had less pain
Quality: 5/5
N=62 on Day 9
Jeffrey and Patients undergoing Arnica D6 tablets and Placebo Level of pain “Reduced hand discomfort
Belcher (2002) carpal tunnel release ointment following during Week 2 despite the
[Level II] procedures endoscopic carpal tunnel use of higher potency Arnica
d release (bilateral), three and preoperative
Quality: 5/5
N=37 times per day medication”
Abbreviations: AMSTAR, Assessment of Multiple Systematic Reviews; CAM, complementary and alternative medicines; C, centesimal; D, decimal; SR, systematic review; SRL, undefined. This is
the name of the homeopathic gel; VAS, visual analogue scale.
a
Level of evidence as assessed by the evidence reviewer.
b
Study quality as assessed by the evidence reviewer using the AMSTAR measurement toolkit.
c
Study quality as reported in the systematic review.
d
Study quality as assessed using the Oxford Quality Score. The higher the quality score out of 5, the higher the quality of the study.
5 Discussion
could not have demonstrated “equivalence” between treatments. As a result, claims of equivalence
must be interpreted with caution. Because of the shortcomings within the primary studies, the
overall completeness and quality of the systematic reviews was also limited.
Several systematic reviews were identified that examined the effectiveness of homeopathy for
multiple clinical conditions as described in Section 4.2. In some of these reviews, an overall
conclusion was often drawn instead of specific conclusions for each clinical condition. Other
systematic reviews were broad reviews of various CAM, including homeopathy, for the treatment of
a particular clinical condition or specific clinical area. In these cases, the level of detail provided on
the homeopathy studies was often limited. Some systematic reviews (Cucherat et al 2000; Linde et al
1997; Linde and Melchart 1998) also performed a ‘mega’ meta-analysis of the effectiveness of
homeopathy across clinical conditions, often without separate presentation of the meta-analysed
results for the individual clinical conditions. The appropriateness of these meta-analyses is
questionable as the included studies were highly heterogeneous in terms of the investigated clinical
condition, study design, intervention, comparator, outcomes reported and overall quality.
Publication bias may also have impacted the findings of the evidence review. Although many of the
systematic review authors acknowledged the risk of publication bias, very few attempted to quantify
the likelihood that publication bias affected the overall evidence base (using graphical aids or
statistical tests). Publication bias is a complex issue, particularly for therapies such as homeopathy.
Journals of complementary and alternative medicines may be more likely to publish trials with
positive findings, despite significant methodological flaws; whereas mainstream medical journals
may tend to publish more rigorous trials with negative results. There is also the possibility that the
mainstream journals would not publish homeopathy trials with negative results, as the publication of
such trials could be perceived to be of little relevance or interest for the mainstream on the basis
that the field of homeopathy as a whole has already been deemed to be inefficacious and
unscientific (Barnes et al 1997). Indeed, in an investigation of 110 homeopathy trials, Shang et al
(2005) noted that sources of heterogeneity included the language of publication (more beneficial
effects in trials published in languages other than English), indexing in MEDLINE (more beneficial
effects in trials not indexed in MEDLINE) and indicators of trial quality (more beneficial effects in
trials of lower quality). Importantly, smaller trials and those of lower quality showed more beneficial
treatment effect of homeopathy than larger and higher quality trials (Shang et al, 2005).
5.3 Limitations
Although the approach adopted in this overview of systematic reviews guarantees that the widest
possible range of high-quality evidence is identified and included, it is limited by the quality of the
included systematic reviews. Many of the systematic reviews inadequately reported the included
trials and it was often difficult to ascertain details as to the length of follow up, the outcomes
examined, and the statistical and clinical significance of the results. Indeed, the authors of the
reviews often commented on the poor reporting and serious methodological flaws of the included
studies. The quality assessment of included primary trials sometimes differed between systematic
reviews making it difficult to determine if the apparent inadequacies of the systematic reviews were,
in fact, shortcomings of the included trials or of the reviews themselves.
The evidence reviewer would argue that the overview process was limited by elements of poor
reporting and flawed methodology in the primary studies, exacerbated by incomplete reporting in
the systematic reviews. The classification of primary studies as Level II or Level III-2 studies also relied
on information reported in the systematic reviews. As a result of these limitations, the evidence
reviewers did not place a “high” level of confidence in the evidence base for any clinical condition,
and the majority of conditions were associated with “low” or “very low” levels of confidence.
The evidence reviewers acknowledge that a limitation to this overview was the assessment of
‘effectiveness’ based on statistical significance and not clinical significance. This was, however,
necessary due to the poor reporting and lack of analyses by the included systematic reviews and
primary studies. Without the reporting of intervention effects, decisions could not be made about
the clinical importance of the intervention.
Another limitation was the process by which outcomes were aggregated in order to determine the
overall effectiveness of homeopathy for each clinical condition. Ideally, the overview would have
included one evidence statement for each outcome within each clinical condition. However, this was
not possible due to the large number of outcomes and variable reporting of those outcomes
between the different systematic reviews. As a result, outcomes were aggregated in order to
formulate one evidence statement per clinical condition. It was also not possible to create a
hierarchy of clinically relevant outcomes prior to conducting the overview because the clinical
conditions that would ultimately be included in the Overview Report were not known. Although it
would have been possible to prioritise outcomes post hoc, such a process would have been subject
to bias and was therefore avoided. Consequently, all outcomes reported in the systematic reviews
were taken into account when the evidence statements were formulated unless the HWC
determined that a particular outcome had no clinical relevance.
Additionally, it was difficult for the evidence reviewer to compare the quality of primary studies that
had been examined in different systematic reviews. This limitation stemmed from the fact that the
systematic reviewers often used different scoring systems to rate the quality of the individual studies
(e.g. risk of bias assessments vs Jadad scores). The various scoring systems are inherently different
and likening a ‘poor’ quality trial based on one scoring system to a ‘poor’ quality trial based on
another system is problematic. Nevertheless, the evidence reviewer felt that it was necessary to
comment on the quality of the individual studies in the evidence statements and, as a result, various
scoring systems have been used for the comparison of study quality.
A further limitation of the overview process is that no attempt was made to systematically identify
any recent Level II studies that may not have been included in a systematic review, but met the
inclusion criteria described in the primary clinical research question. An additional report was
produced by the evidence reviewer that accompanies this Overview Report that considers the
evidence from literature submitted to NHMRC in 2011 by the Australian Homoeopathy Association,
the Australian Medical Fellowship of Homeopathy and members of the public that was not otherwise
considered in the Overview Report. The ‘Review of Submitted Literature’ identified eight Level II
studies and one Level III-2 study that were not included in the Overview Report. However, these
studies remain a self-selected sample and other literature concerning the effectiveness of
homeopathy for a specific clinical condition has not been systematically retrieved.
Due to the broad scope of the overview and the large number of clinical conditions identified, it was
not possible to separate evidence for the different types of homeopathic regimens (clinical or
individualized, practitioner-prescribed or self-prescribed) utilized in the primary studies. Details
regarding the homeopathic interventions under investigation were often lacking in the systematic
reviews. Similarly, comparators were generally not well described. Many primary studies investigated
individualised homeopathy as the intervention. Whilst individualisation of therapy allows
Prepared for the NHMRC Homeopathy Working Committee by Optum 286
EFFECTIVENESS OF HOMEOPATHY FOR CLINICAL CONDITIONS: OVERVIEW REPORT October 2013
homeopathy to be practiced in its traditional fashion, this increases the complexity of comparing
outcomes and determining the efficacy of specific homeopathic regimens. Importantly, information
regarding the nature of the consultation between patients and homeopaths (if any) was rarely
provided. This is important as there is evidence for the therapeutic benefits of the consultation
process on health outcomes in both conventional medicine and CAM (Brien et al 2011; Di Blasi et al
2002; Walach 2003), which draws into question the effectiveness of the homeopathic medicine per
se as opposed to the interaction between patients and homeopaths.
Finally, the systematic reviews did not discuss the use of active comparators or provide a critique of
whether or not the authors of the studies had chosen appropriate or clinically effective ‘active’
comparators. For example, homeopathy was compared with diazepam (Valium) as a treatment for
depression (Heulluy 1985 in Pilkington et al 2005), ‘standard care’ included antibiotics and nasal
sprays as a treatment of children with otitis media (Kruse 1998 in Bellavite et al 2011) and
homeopathy was compared with chloroquine for the treatment of malaria (van Erp and Brands 1996
in Linde and Melchart 1998). A discussion regarding the appropriateness of these and other active
comparators within the systematic reviews would have been beneficial in order to put the results for
homeopathy in context.
Justify the use of active comparators and comment on the effectiveness of those
comparators compared to placebo
Use a methodological approach that can differentiate between the effect of homeopathic
medicines and treatment by a homeopath (i.e. interaction at a consultation)
6 Conclusion
There is a paucity of good-quality studies of sufficient size that examine the effectiveness of
homeopathy as a treatment for any clinical condition in humans. The available evidence is not
compelling and fails to demonstrate that homeopathy is an effective treatment for any of the
reported clinical conditions in humans.
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National Collaborating Centre for Cancer (UK). Early and locally advanced breast cancer: diagnosis and
treatment. Cardiff (UK): National Collaborating Centre for Cancer; 2009 Feb. (NICE Clinical Guidelines, No.
80).
Notes: Full text review. Excluded. Wrong intervention
National Collaborating Centre for Chronic Conditions (UK). Chronic heart failure. London: Royal College of
Physicians; 2003. (NICE Clinical Guidelines, No. 5).
Notes: Full text review. Excluded. Wrong intervention
National Collaborating Centre for Chronic Conditions (UK). Multiple sclerosis. London: Royal College of
Physicians; 2004. (NICE Clinical Guidelines, No. 8).
Notes: Full text review. Excluded. Wrong intervention
National Collaborating Centre for Chronic Conditions (UK). Rheumatoid arthritis: national clinical guideline for
management and treatment in adults. London: Royal College of Physicians; 2009 Feb. (NICE Clinical
Guidelines, No. 79).
Notes: Full text review. Excluded. Wrong intervention
National Collaborating Centre for Mental Health (UK). Generalised anxiety disorder in adults: management in
primary, secondary and community care. Leicester (UK): British Psychological Society; 2011. (NICE Clinical
Guidelines, No. 113).
Notes: Full text review. Excluded. Wrong intervention
National Collaborating Centre for Mental Health (UK). Obsessive-compulsive disorder: core intervention in the
treatment of obsessive compulsive disorder and body dysmorphic disorder. Leicester (UK): British
Psychological Society; 2006. (NICE Clinical Guidelines, No. 31).
Notes: Full text review. Excluded. Wrong publication type
National Collaborating Centre for Mental Health (UK). Psychosis with coexisting substance misuse. Leicester
(UK): British Psychological Society; 2011. (NICE Clinical Guidelines, No. 120).
Notes: Full text review. Excluded. Wrong intervention
National Collaborating Centre for Primary Care (UK). Postnatal care: routine postnatal care of women and their
babies. London: Royal College of General Practitioners; 2006 Jul. (NICE Clinical Guidelines, No. 37).
Notes: Full text review. Excluded. Wrong intervention
National Collaborating Centre for Women’s and Children’s Health (UK). Antenatal care. London: Royal College
of Obstetricians and Gynaecologists Press; 2008 Mar. (NICE Clinical Guidelines, No. 62).
Notes: Full text review. Excluded. Wrong intervention
National Collaborating Centre for Women’s and Children’s Health (UK). Atopic eczema in children. London:
Royal College of Obstetricians and Gynaecologists Press; 2007 Dec. (NICE Clinical Guidelines, No. 57).
Notes: Full text review. Excluded. Wrong publication type
National Collaborating Centre for Women’s and Children’s Health (UK). Caesarean section. London: Royal
College of Obstetricians and Gynaecologists Press; 2011 Nov. (NICE Clinical Guidelines, No. 132).
Notes: Full text review. Excluded. Wrong intervention
National Collaborating Centre for Women’s and Children’s Health (UK). Fertility: assessment and treatment for
people with fertility problems. London: Royal College of Obstetricians and Gynaecologists Press; 2004 Feb.
(NICE Clinical Guidelines, No. 11).
Notes: Full text review. Excluded. Wrong intervention
National Collaborating Centre for Women’s and Children’s Health (UK). Induction of labour. London: Royal
College of Obstetricians and Gynaecologists Press; 2008 Jul. (NICE Clinical Guidelines, No. 70). Notes: Full
text review. Excluded. Wrong publication type
National Collaborating Centre for Women’s and Children’s Health (UK). Intrapartum care: care of healthy
women and their babies during childbirth. London: Royal College of Obstetricians and Gynaecologists
Press; 2007 Sept. (NICE Clinical Guidelines, No. 55).
Notes: Full text review. Excluded. Wrong intervention
National Collaborating Centre for Women’s and Children’s Health (UK). Neonatal jaundice. London: Royal
College of Obstetricians and Gynaecologists Press; 2010 May. (NICE Clinical Guidelines, No. 98).
Notes: Full text review. Excluded. Wrong publication type
Paterson C (1998) Meta-analysis of homoeopathy trials. Lancet 351(9099):365-6.
Notes: Full text review. Excluded. Wrong publication type
Peckham EJ, -Nelson-E-Andrea, Greenhalgh J, Cooper K, Roberts ER, Agrawal A (2012) Homeopathy for
treatment of irritable bowel syndrome. Cochrane Database Syst Rev.
Notes: Full text review. Excluded. Wrong publication type
Pilkington K (2007) Searching for CAM evidence: An evaluation of therapy-specific search strategies. J Altern
Complement Med 13(4):451-9.
Notes: Full text review. Excluded. Wrong outcomes
Pittler MH, Ernst E (2005) Complementary therapies for reducing body weight: A systematic review. Int J Obes
29(9):1030-8.
Notes: Full text review. Excluded. Wrong outcomes
Posadzki P, Alotaibi A, Ernst E (2012) Adverse effects of homeopathy: A systematic review of published case
reports and case series. Int J Clin Pract 66(12):1178-88.
Notes: Full text review. Excluded. Wrong publication type
Posadzki P, Lee MS, Ernst E (2012) Complementary and alternative medicine for diabetes mellitus: An overview
of systematic reviews. Focus Altern Complement Ther 17(3):142-8.
Notes: Full text review. Excluded. Wrong publication type
Rao AM, Fitzgerald-James EF, Ahmed I (2011) Role of homeopathic medicines in prevention and treatment of
paralytic ileus. Cochrane Database Syst Rev.
Notes: Full text review. Excluded. Wrong publication type
Reid SF, Chalder T, Cleare A, Hotopf M, Wessely S (2008) Chronic fatigue syndrome. Clin Evid (Online) 2008.
Notes: Full text review. Excluded. Superseded publication
Reznik M, Ozuah PO (2005) CAM in the treatment of paediatric asthma. Focus Altern Complement Ther
10(3):177-80.
Notes: Full text review. Excluded. Wrong publication type
Robinson L, Hutchings D, Dickinson HO, Corner L, Beyer F, Finch T, Hughes J, Vanoli A, Ballard C, Bond J (2007)
Effectiveness and acceptability of non-pharmacological interventions to reduce wandering in dementia: A
systematic review. Int J Geriatr Psychiatry 22(1):9-22.
Notes: Full text review. Excluded. Wrong intervention
Rodriguez-Caballero A, Torres-Lagares D, Robles-Garcia M, Pachon-Ibanez J, Gonzalez-Padilla D, Gutierrez-Perez
JL (2012) Cancer treatment-induced oral mucositis: a critical review. Int J Oral Maxillofac Surg 41(2):225-
38.
Notes: Full text review. Excluded. Wrong publication type
Rutten ALB, Stolper CF (2008) The 2005 meta-analysis of homeopathy: the importance of post-publication data.
Homeopathy 97(4):169-77.
Notes: Full text review. Excluded. Wrong publication type
Sarris J, Moylan S, Camfield DA, Pase MP, Mischoulon D, Berk M, Jacka FN, Schweitzer I (2012) Complementary
medicine, exercise, meditation, diet, and lifestyle modification for anxiety disorders: A review of current
evidence. Evid -Based Complement Altern Med 2012.
Notes: Full text review. Excluded. Wrong publication type
Schafer T (2010) Complementary alternative medicine (CAM) and atopic eczema. Allergologie 33(4):180-9.
Notes: Full text review. Excluded. Wrong publication type
Schneider B, Klein P, Weiser M (2005) Treatment of vertigo with a homeopathic complex remedy compared
with usual treatments: A meta-analysis of clinical trials. Arzneim -Forsch Drug Res 55(1):23-9.
Notes: Full text review. Excluded. Wrong publication type
Searight HR, Robertson K, Smith T, Searight BK (2011) A qualitative systematic review of complementary and
alternative therapies for childhood attention deficit hyperactivity disorder: Botanicals, diet, minerals, and
homeopathy. Fam Med Prim Care Rev 13(4):798-803.
Notes: Full text review. Excluded. Wrong intervention
Seidl MM, Stewart DE (1998) Alternative treatments for menopausal symptoms. Systematic review of scientific
and lay literature. Can Fam Physician 44:1299-308.
Notes: Full text review. Excluded. Did not provide appraisal of primary studies (criterion 7 of AMSTAR)
Semple MG, Smyth RL (2003) Update on Cochrane data on paediatric respiratory diseases. Paediatr Respir Rev
4(3):250-66.
Notes: Full text review. Excluded. Wrong publication type
Shang A, Huwiler-Muntener K, Nartey L, Juni P, Dorig S, Sterne JA, Pewsner D, Egger M (2005) Are the clinical
effects of homoeopathy placebo effects? Comparative study of placebo-controlled trials of homoeopathy
and allopathy. Lancet 366(9487):726-32.
Notes: Full text review. Excluded. Wrong outcomes
Shekelle PG, Takata G, Newberry SJ, Coker T, Limbos M, Chan LS, Timmer M, Suttorp M, Carter J, Motala A,
Valentine D, Johnsen B, Shanman R. Management of Acute Otitis Media: Update. Evidence
Report/Technology Assessment No. 198. (Prepared by the RAND Evidence-Based Practice Center under
Contract No. 290 2007 10056 I). Rockville, MD: Agency for Healthcare Research and Quality. November
2010.
Notes: Full text review. Excluded. Wrong intervention
Sherr J, Quirk T (2007) Systematic review of homeopathic pathogenetic trials: an excess of rigour? Homeopathy
96(4):273-5.
Notes: Full text review. Excluded. Wrong publication type
Soeken KL (2004) Selected CAM Therapies for Arthritis-Related Pain: The Evidence from Systematic Reviews.
Clin J Pain 20(1):13-8.
Notes: Full text review. Excluded. Wrong publication type
Steurer-Stey C, Russi EW, Steurer J (2002) Complementary and alternative medicine in asthma: do they work?
Swiss Med Wkly 132(25-26):338-44.
Notes: Full text review. Excluded. Wrong publication type
Strauss JL, Coeytaux R, McDuffie J, Nagi A, Williams JW Jr. Efficacy of Complementary and Alternative Therapies
for Posttraumatic Stress Disorder. VA-ESP Project #09-010; 2011.
Notes: Full text review. Excluded. Wrong intervention
Struijs P, Kerkhoffs G (2007) Ankle sprain. Clin Evid (Online) 2007.
Notes: Full text review. Excluded. Superseded publication
Struijs PA, Kerkhoffs GM (2010) Ankle sprain. Clin Evid (Online) 2010.
Notes: Full text review. Excluded. Wrong publication type
Stub T, Musial F, Alraek T (2012) Adverse effects of homeopathy, what do we know? A systematic review. BMC
Complement Altern Med 12.
Notes: Full text review. Excluded. Wrong publication type
Terry R, Perry R, Ernst E (2012) An overview of systematic reviews of complementary and alternative medicine
for fibromyalgia. Clin Rheumatol 31(1):55-66.
Notes: Full text review. Excluded. Wrong publication type
Thachil AF, Mohan R, Bhugra D (2007) The evidence base of complementary and alternative therapies in
depression. J Affect Disord 97(1-3):23-35.
Notes: Full text review. Excluded. Wrong intervention
Ullman D (2003) Controlled clinical trials evaluating the homeopathic treatment of people with human
immunodeficiency virus or acquired immune deficiency syndrome. J Altern Complement Med 9(1):133-41.
Notes: Full text review. Excluded. Wrong publication type
Vallance AK, Jobst KA (1998) Meta-analysis of homoeopathy trials. Lancet 351(9099):366-8.
Notes: Full text review. Excluded. Wrong publication type
Van Den Biggelaar FJHM, Smolders J, Jansen JFA (2010) Complementary and alternative medicine in alopecia
areata. Am J Clin Dermatol 11(1):11-20.
Notes: Full text review. Excluded. Wrong intervention
van der Wouden JC, Menke J, Gajadin S, Koning S, Tasche MJ, van Suijlekom-Smit LW, Berger MY, Butler CC
(2006) Interventions for cutaneous molluscum contagiosum. Cochrane Database Syst Rev(2):CD004767.
Notes: Full text review. Excluded. Superseded publication
van der Wouden JC, van der Sande R, van Suijlekom-Smit LW, Berger M, Butler C, Koning S (2009) Interventions
for cutaneous molluscum contagiosum. Cochrane Database Syst Rev(4):CD004767.
Notes: Full text review. Excluded. Wrong intervention
Van Wijk R (2007) The in vitro evidence for an effect of high homeopathic potencies-A systematic review of the
literature. Complement Ther Med 15(2):139-41.
Notes: Full text review. Excluded. Wrong publication type
Vickers AJ, Smith C (2000) Homoeopathic Oscillococcinum for preventing and treating influenza and influenza-
like syndromes. Cochrane Database Syst Rev(2):CD001957.
Notes: Full text review. Excluded. Superseded publication
Vickers AJ, Smith C (2004) Homoeopathic Oscillococcinum for preventing and treating influenza and influenza-
like syndromes. Cochrane Database Syst Rev(1):CD001957.
Notes: Full text review. Excluded. Superseded publication
Vickers AJ, Smith C (2006) Homoeopathic Oscillococcinum for preventing and treating influenza and influenza-
like syndromes (Review). Cochrane Database Syst Rev(3).
Notes: Full text review. Excluded. Superseded publication
Walach H (2002) Homeopathy in rheumatoid arthritis - No evidence for its superiority to placebo. Forsch
Komplementarmed Klass Naturheilkd 9(6):363-5.
Notes: Full text review. Excluded. Wrong publication type
Warren Z, Veenstra-VanderWeele J, Stone W, Bruzek JL, Nahmias AS, Foss-Feig JH, Jerome RN, Krishnaswami S,
Sathe NA, Glasser AM, Surawicz T, McPheeters ML. Therapies for Children With Autism Spectrum
Disorders. Comparative Effectiveness Review No. 26. (Prepared by the Vanderbilt Evidence-based Practice
Center under Contract No. 290-2007-10065-I.) AHRQ Publication No. 11-EHC029-EF. Rockville, MD:
Agency for Healthcare Research and Quality. April 2011. Available at:
www.effectivehealthcare.ahrq.gov/reports/final.cfm.
Notes: Full text review. Excluded. Wrong intervention
Weiner DK, Ernst E (2004) Complementary and alternative approaches to the treatment of persistent
musculoskeletal pain. Clin J Pain 20(4):244-55.
Notes: Full text review. Excluded. Wrong publication type
Whitlock EP, O’Connor EA, Williams SB, Beil TL, Lutz KW. Effectiveness of Primary Care Interventions for Weight
Management in Children and Adolescents: An Updated, Targeted Systematic Review for the USPSTF.
Evidence synthesis No. 76. AHRQ Publication No. 10-05144-EF-1. Rockville, Maryland: Agency for
Healthcare Research and Quality, January 2010.
Notes: Full text review. Excluded. Wrong intervention
Wiesenauer ML, Ludtke R (2000) A meta-analysis of the homeopathic treatment of pollinosis with Galphimia
glauca. Br Homeopath J 89(SUPPL. 1):S52.
Notes: Full text review. Excluded. Wrong publication type
Witt CM, Bluth M, Albrecht H, Weisshuhn TER, Baumgartner S, Willich SN (2007) The in vitro evidence for an
effect of high homeopathic potencies-A systematic review of the literature. Complement Ther Med
15(2):128-38.
Notes: Full text review. Excluded. Wrong outcomes
Yaju Y, Kataoka Y, Eto H, Horiuchi S, Mori R (2011) Prophylactic interventions after delivery of placenta for
reducing bleeding during the postnatal period. Cochrane Database Syst Rev.
Notes: Full text review. Excluded. Wrong publication type
Zochling J (2004) Complementary and alternative medicines and arthritis. Med Today 5(9):63-6.
Notes: Full text review. Excluded. Wrong publication type
World Health Organization (2009). Safety issues in the preparation of homeopathic medicines. WHO Press,
Geneva.