Public sector low threshold office-based

buprenorphine treatment: outcomes at year 7




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Bhatraju, E., Grossman, E., Tofighi, B., McNeely, J.,
DiRocco, D., Flannery, M., Garment, A., Goldfeld, K.,
Gourevitch, M., Lee, J. (2017). Public sector low
threshold office-based buprenorphine treatment:
outcomes at year 7 Addiction Science & Clinical
Practice 12(1), 7. https://dx.doi.org/10.1186/
s13722-017-0072-2

Link to download PDF

Link to Pubmed
 Medications for Opioid Use Disorder: For Healthcare and Addiction
Professionals, Policymakers, Patients, and Families [Internet]


Foreward: The Substance Abuse and Mental Health Services Administration (SAMHSA) is the U.S.
Department of Health and Human Services agency that leads public health efforts to advance the behavioral
health of the nation. SAMHSA's mission is to reduce the impact of substance abuse and mental illness on
America's communities.


The Treatment Improvement Protocol (TIP) series fulfills SAMHSA's mission by providing science-based best-
practice guidance to the behavioral health field. TIPs reflect careful consideration of all relevant clinical and
health service research, demonstrated experience, and implementation requirements. Select nonfederal
clinical researchers, service providers, program administrators, and patient advocates comprising each TIP's
consensus panel discuss these factors, offering input on the TIP's specific topic in their areas of expertise to
reach consensus on best practices. Field reviewers then assess draft content.

The talent, dedication, and hard work that TIP panelists and reviewers bring to this highly participatory process
have helped bridge the gap between the promise of research and the needs of practicing clinicians and
Substance Abuse and Mental Health Services
administrators to serve, in the most scientifically sound and effective ways, people in need of behavioral health
Administration. Medications for Opioid Use Disorder.
Treatment Improvement Protocol (TIP) Series 63, Full
services. We are grateful to all who have joined with us to contribute to advances in the behavioral health field.

Document. HHS Publication No. (SMA) 18-

5063FULLDOC. Rockville, MD: Substance Abuse and
Mental Health Services Administration, 2018. Executive Summary: The goal of treatment for opioid addiction or opioid use disorder (OUD) is remission of
the disorder leading to lasting recovery. Recovery is a process of change through which individuals improve
their health and wellness, live self-directed lives, and strive to reach their full potential.1 This Treatment
Link to download PDF Improvement Protocol (TIP) reviews the use of the three Food and Drug Administration (FDA)-approved
medications used to treat OUD—methadone, naltrexone, and buprenorphine—and the other strategies and
services needed to support recovery for people with OUD.

Link to Pubmed
 Public sector low threshold office-based

buprenorphine treatment: outcomes at year 7


 BACKGROUND: Buprenorphine maintenance for opioid dependence remains of limited availability among
underserved populations, despite increases in US opioid misuse and overdose deaths. Low threshold primary care
treatment models including the use of unobserved, "home," buprenorphine induction may simplify initiation of care
and improve access. Unobserved induction and long-term treatment outcomes have not been reported recently
among large, naturalistic cohorts treated in low threshold safety net primary care settings.

METHODS: This prospective clinical registry cohort design estimated rates of induction-related adverse events,
treatment retention, and urine opioid results for opioid dependent adults offered buprenorphine maintenance in a
New York City public hospital primary care office-based practice from 2006 to 2013. This clinic relied on typical
ambulatory care individual provider-patient visits, prescribed unobserved induction exclusively, saw patients no
more than weekly, and did not require additional psychosocial treatment. Unobserved induction consisted of an in-
person screening and diagnostic visit followed by a 1-week buprenorphine written prescription, with pamphlet, and
telephone support. Primary outcomes analyzed were rates of induction-related adverse events (AE), week 1 drop-
out, and long-term treatment retention. Factors associated with treatment retention were examined using a Cox
proportional hazard model among inductions and all patients. Secondary outcomes included overall clinic
Bhatraju, E., Grossman, E., Tofighi, B., McNeely, J.,
DiRocco, D., Flannery, M., Garment, A., Goldfeld, K.,
retention, buprenorphine dosages, and urine sample results.

Gourevitch, M., Lee, J. (2017). Public sector low

threshold office-based buprenorphine treatment:
outcomes at year 7 Addiction Science & Clinical RESULTS: Of the 485 total patients in our registry, 306 were inducted, and 179 were transfers already on
Practice 12(1), 7. https://dx.doi.org/10.1186/
s13722-017-0072-2
buprenorphine. Post-induction (n = 306), week 1 drop-out was 17%. Rates of any induction-related AE were 12%;
serious adverse events, 0%; precipitated withdrawal, 3%; prolonged withdrawal, 4%. Treatment retention was a
median 38 weeks (range 0-320) for inductions, compared to 110 (0-354) weeks for transfers and 57 for the entire
clinic population. Older age, later years of first clinic visit (vs. 2006-2007), and baseline heroin abstinence were
Link to download PDF associated with increased treatment retention overall.

CONCLUSIONS: Unobserved "home" buprenorphine induction in a public sector primary care setting appeared a
feasible and safe clinical practice. Post-induction treatment retention of a median 38 weeks was in line with
Link to Pubmed previous naturalistic studies of real-world office-based opioid treatment. Low threshold treatment protocols, as
compared to national guidelines, may compliment recently increased prescriber patient limits and expand access
to buprenorphine among public sector opioid use disorder patients.
 Anesthesia-assisted vs buprenorphine- or clonidine-assisted
heroin detoxification and naltrexone induction: a randomized trial

 CONTEXT: Rapid opioid detoxification with opioid antagonist induction using general anesthesia has emerged as an
expensive, potentially dangerous, unproven approach to treat opioid dependence.

OBJECTIVE: To determine how anesthesia-assisted detoxification with rapid antagonist induction for heroin dependence
compared with 2 alternative detoxification and antagonist induction methods.

DESIGN, SETTING, AND PATIENTS: A total of 106 treatment-seeking heroin-dependent patients, aged 21 through 50 years,
were randomly assigned to 1 of 3 inpatient withdrawal treatments over 72 hours followed by 12 weeks of outpatient naltrexone
maintenance with relapse prevention psychotherapy. This randomized trial was conducted between 2000 and 2003 at
Columbia University Medical Center's Clinical Research Center. Outpatient treatment occurred at the Columbia University
research service for substance use disorders. Patients were included if they had an American Society of Anesthesiologists
physical status of I or II, were without major comorbid psychiatric illness, and were not dependent on other drugs or alcohol.

INTERVENTIONS: Anesthesia-assisted rapid opioid detoxification with naltrexone induction, buprenorphine-assisted rapid
opioid detoxification with naltrexone induction, and clonidine-assisted opioid detoxification with delayed naltrexone induction.

Collins, E., Kleber, H., Whittington, R., Heitler, N.

MAIN OUTCOME MEASURES: Withdrawal severity scores on objective and subjective scales; proportions of patients
(2005). Anesthesia-Assisted vs Buprenorphine- or receiving naltrexone, completing inpatient detoxification, and retained in treatment; proportion of opioid-positive urine
Clonidine-Assisted Heroin Detoxification and
Naltrexone Induction: A Randomized Trial JAMA
specimens.

294(8), 903-913. https://dx.doi.org/10.1001/jama.

294.8.903 RESULTS: Mean withdrawal severities were comparable across the 3 treatments. Compared with clonidine-assisted
detoxification, the anesthesia- and buprenorphine-assisted detoxification interventions had significantly greater rates of
naltrexone induction (94% anesthesia, 97% buprenorphine, and 21% clonidine), but the groups did not differ in rates of
completion of inpatient detoxification. Treatment retention over 12 weeks was not significantly different among groups with 7
Link to download PDF of 35 (20%) retained in the anesthesia-assisted group, 9 of 37 (24%) in the buprenorphine-assisted group, and 3 of 34 (9%) in
the clonidine-assisted group. Induction with 50 mg of naltrexone significantly reduced the risk of dropping out (odds ratio,
0.28; 95% confidence interval, 0.15-0.51). There were no significant group differences in proportions of opioid-positive urine
specimens. The anesthesia procedure was associated with 3 potentially life-threatening adverse events.

Link to Pubmed CONCLUSION:

These data do not support the use of general anesthesia for heroin detoxification and rapid opioid antagonist induction.　O
 Risk of death during and after opiate substitution treatment in primary care:
prospective observational study in UK General Practice Research Database

 OBJECTIVE: To investigate the effect of opiate substitution treatment at the beginning and end of treatment and
according to duration of treatment.

DESIGN: Prospective cohort study. Setting UK General Practice Research Database.

PARTICIPANTS: Primary care patients with a diagnosis of substance misuse prescribed methadone or
buprenorphine during 1990-2005. 5577 patients with 267 003 prescriptions for opiate substitution treatment
followed-up (17 732 years) until one year after the expiry of their last prescription, the date of death before this time
had elapsed, or the date of transfer away from the practice.

MAIN OUTCOME MEASURES: Mortality rates and rate ratios comparing periods in and out of treatment adjusted
for sex, age, calendar year, and comorbidity; standardised mortality ratios comparing opiate users' mortality with
general population mortality rates.

RESULTS: Crude mortality rates were 0.7 per 100 person years on opiate substitution treatment and 1.3 per 100
Cornish, R., Macleod, J., Strang, J., Vickerman, P., person years off treatment; standardised mortality ratios were 5.3 (95% confidence interval 4.0 to 6.8) on treatment
Hickman, M. (2010). Risk of death during and after
opiate substitution treatment in primary care: and 10.9 (9.0 to 13.1) off treatment. Men using opiates had approximately twice the risk of death of women
prospective observational study in UK General
Practice Research Database BMJ : British Medical
(morality rate ratio 2.0, 1.4 to 2.9). In the first two weeks of opiate substitution treatment the crude mortality rate
Journal 341(oct26 2), c5475. https://dx.doi.org/ was 1.7 per 100 person years: 3.1 (1.5 to 6.6) times higher (after adjustment for sex, age group, calendar period,
10.1136/bmj.c5475က and comorbidity) than the rate during the rest of time on treatment. The crude mortality rate was 4.8 per 100
person years in weeks 1-2 after treatment stopped, 4.3 in weeks 3-4, and 0.95 during the rest of time off
treatment: 9 (5.4 to 14.9), 8 (4.7 to 13.7), and 1.9 (1.3 to 2.8) times higher than the baseline risk of mortality during
Link to download PDF treatment. Opiate substitution treatment has a greater than 85% chance of reducing overall mortality among opiate
users if the average duration approaches or exceeds 12 months.

CONCLUSIONS: Clinicians and patients should be aware of the increased mortality risk at the start of opiate
substitution treatment and immediately after stopping treatment. Further research is needed to investigate the
Link to Pubmed effect of average duration of opiate substitution treatment on drug related mortality.
 Mortality Associated With Time in and Out of Buprenorphine Treatment in
French Office-Based General Practice: A 7-Year Cohort Study


Abstract: In France, most cases of opioid use disorder are treated with buprenorphine by
general practitioners in private practice. Using reimbursement data of a representative
sample of the French population, Echantillon Généraliste des Bénéficiaires, we
investigated mortality during periods when patients were in and out of treatment in a
cohort of 713 new users of buprenorphine having a mean (SD) follow-up of 4.5 (1.5) years.
The mortality rate was 0.63 per 100 person-years (95% CI, 0.40-0.85) overall. In a
multivariate Cox regression model, compared with being in treatment, being out of
treatment was associated with a markedly increased risk of death (hazard ratio = 29.04;
95% CI, 10.04-83.99). Buprenorphine appears to be a strong protective factor against
mortality.

Dupouy, J., Palmaro, A., Fatséas, M., Auriacombe, M.,

Micallef, J., Oustric, S., Lapeyre-Mestre, M. (2017).
Mortality Associated With Time in and Out of
Buprenorphine Treatment in French Office-Based
General Practice: A 7-Year Cohort Study The Annals of
Family Medicine  15(4), 355-358. https://dx.doi.org/
10.1370/afm.2098

Link to download PDF

Link to Pubmed
 Mortality among individuals accessing pharmacological treatment for
opioid dependence in California, 2006-10

 AIMS: To estimate mortality rates among treated opioid-dependent individuals by cause and in relation to the
general population, and to estimate the instantaneous effects of opioid detoxification and maintenance
treatment (MMT) on the hazard of all-cause and cause-specific mortality.

DESIGN: Population-based treatment cohort study.

SETTING: Linked mortality data on all individuals first enrolled in publicly funded pharmacological treatment
for opioid dependence in California, USA from 2006 to 2010.

PARTICIPANTS: A total of 32 322 individuals, among whom there were 1031 deaths (3.2%) over a median
follow-up of 2.6 years (interquartile range = 1.4-3.7).

MEASUREMENTS: The primary outcome was mortality, indicated by time to death, crude mortality rates
(CMR) and standardized mortality ratios (SMR).

Dupouy, J., Palmaro, A., Fatséas, M., Auriacombe, M.,

Micallef, J., Oustric, S., Lapeyre-Mestre, M. (2017).
Mortality Associated With Time in and Out of FINDINGS: Individuals being treated for opioid dependence had a more than fourfold increase of mortality
Buprenorphine Treatment in French Office-Based
General Practice: A 7-Year Cohort Study The Annals of risk compared with the general population [SMR = 4.5, 95% confidence interval (CI) = 4.2, 4.8]. Mortality risk
Family Medicine  15(4), 355-358. https://dx.doi.org/
10.1370/afm.2098 was higher (1) when individuals were out-of-treatment (SMR = 6.1, 95% CI = 5.7, 6.5) than in-treatment (SMR = 
1.8, 95% CI = 1.6, 2.1) and (2) during detoxification (SMR = 2.4, 95% CI = 1.5, 3.8) than during MMT (SMR = 1.8,
95% CI = 1.5, 2.1), especially in the 2 weeks post-treatment entry (SMR = 5.5, 95% CI = 2.7, 9.8 versus SMR = 
Link to download PDF 2.5, 95% CI = 1.7, 4.9). Detoxification and MMT both independently reduced the instantaneous hazard of all-
cause and drug-related mortality. MMT preceded by detoxification was associated with lower all-cause and
other cause-specific mortality than MMT alone.

Link to Pubmed CONCLUSIONS: In people with opiate dependence, detoxification and methadone maintenance treatment
both independently reduce the instantaneous hazard of all-cause and drug-related mortality.

 Mortality
Risk of deathPublic
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Utilizing sector
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pharmacological treatment
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buprenorphine-naloxone treatment
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buprenorphine ininUK
naltrexone
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California,
prescription-opioid Practice
outcomes Research
year 7 Database
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2006-10
dependence at trial


OBJECTIVES: To review current evidence on buprenorphine-naloxone (bup/nx) for the treatment of
opioid-use disorders, with a focus on strategies for clinical management and office-based patient
care.

QUALITY OF EVIDENCE: Medline and the Cochrane Database of Systematic Reviews were
searched. Consensus reports, guidelines published, and other authoritative sources were also
included in this review. Apart from expert guidelines, data included in this review constitute level 1
evidence.

FINDINGS: Bup/nx is a partial μ-opioid agonist combined with the opioid antagonist naloxone in a
4:1 ratio. It has a lower abuse potential, carries less stigma, and allows for more flexibility than
methadone. Bup/nx is indicated for both inpatient and ambulatory medically assisted withdrawal
Fraser, R., Mauger, S., Gill, K. (2014). Utilizing (acute detoxification) and long-term substitution treatment (maintenance) of patients who have a
buprenorphine–naloxone to treat illicit and
prescription-opioid dependence Neuropsychiatric mild-to-moderate physical dependence. A stepwise long-term substitution treatment with regular
Disease and Treatment  Volume 10(), 587-598. https://
dx.doi.org/10.2147/ndt.s39692

monitoring and follow-up assessment is usually preferred, as it has better outcomes in reducing illicit
opioid use, minimizing concomitant risks such as human immunodeficiency virus and hepatitis C
transmission, retaining patients in treatment and improving global functioning.

Link to download PDF CONCLUSION: Bup/nx is safe and effective for opioid detoxification and substitution treatment. Its
unique pharmaceutical properties make it particularly suitable for office-based maintenance
treatment of opioid-use disorder.

Link to Pubmed
 Long-term outcomes after randomization to buprenorphine/
naloxone versus methadone in a multi-site trial

 AIMS: To compare long-term outcomes among participants randomized to buprenorphine or methadone.

DESIGN, SETTING AND PARTICIPANTS: Follow-up was conducted in 2011-14 of 1080 opioid-dependent
participants entering seven opioid treatment programs in the United States between 2006 and 2009 and
randomized (within each program) to receive open-label buprenorphine/naloxone or methadone for up to 24
weeks; 795 participants completed in-person interviews (~74% follow-up interview rate) covering on average
4.5 years.

MEASUREMENTS: Outcomes were indicated by mortality and opioid use. Covariates included demographics,
site, cocaine use and treatment experiences.

FINDINGS: Mortality was not different between the two randomized conditions, with 23 (3.6%) of 630
participants randomized to buprenorphine having died versus 26 (5.8%) of 450 participants randomized to
methadone. Opioid use at follow-up was higher among participants randomized to buprenorphine relative to
Hser, Y., Evans, E., Huang, D., Weiss, R., Saxon, A., methadone [42.8 versus 31.7% positive opioid urine specimens, P < 0.01, effect size (h) = 0.23 (0.09, 0.38); 5.8
Carroll, K., Woody, G., Liu, D., Wakim, P., Matthews,
A., Hatch-Maillette, M., Jelstrom, E., Wiest, K., days versus 4.4 days of past 30-day heroin use, P < 0.05, effect size (d) = 0.14 (0.00, 0.28)]. Opioid use during
McLaughlin, P. (2016). Long-term outcomes after
randomization to buprenorphine/naloxone versus the follow-up period by randomization condition was also significant (F(7,39,600) = 3.16; P < 0.001) due mainly
methadone in a multi-site trial. Addiction  111(4), 695
705. https://dx.doi.org/10.1111/add.13238
to less treatment participation among participants randomized to buprenorphine than methadone. Less opioid
use was associated with both buprenorphine and methadone treatment (relative to no treatment); no difference
was found between the two treatments. Individuals who are white or used cocaine at baseline responded
better to methadone than to buprenorphine.

Link to download PDF

CONCLUSIONS: There are few differences in long-term outcomes between buprenorphine and methadone
treatment for opioid dependence, and treatment with each medication is associated with a strong reduction in
opioid use.

Link to Pubmed
 Methadone maintenance therapy versus no opioid replacement
therapy for opioid dependence

 BACKGROUND: Methadone maintenance was the first widely used opioid replacement therapy to treat heroin dependence, and it
remains the best-researched treatment for this problem. Despite the widespread use of methadone in maintenance treatment for
opioid dependence in many countries, it is a controversial treatment whose effectiveness has been disputed.

OBJECTIVES: To evaluate the effects of methadone maintenance treatment (MMT) compared with treatments that did not involve
opioid replacement therapy (i.e., detoxification, offer of drug-free rehabilitation, placebo medication, wait-list controls) for opioid
dependence.

SEARCH STRATEGY: We searched the following databases up to Dec 2008: the Cochrane Controlled Trials Register, EMBASE,
PubMED, CINAHL, Current Contents, Psychlit, CORK [www. state.vt.su/adap/cork], Alcohol and Drug Council of Australia (ADCA)
[www.adca.org.au], Australian Drug Foundation (ADF-VIC) [www.adf.org.au], Centre for Education and Information on Drugs and
Alcohol (CEIDA) [www.ceida.net.au], Australian Bibliographic Network (ABN), and Library of Congress databases, available NIDA
monographs and the College on Problems of Drug Dependence Inc. proceedings, the reference lists of all identified studies and
published reviews; authors of identified RCTs were asked about other published or unpublished relevant RCTs.

SELECTION CRITERIA: All randomized controlled clinical trials of methadone maintenance therapy compared with either placebo
Mattick RP, Breen C, Kimber J, Davoli M. Methadone
maintenance or other non-pharmacological therapy for the treatment of opioid dependence.

maintenance therapy versus no opioid replacement

therapy for opioid dependence. Cochrane Database of
Systematic Reviews 2009, Issue 3. Art. No.:
DATA COLLECTION AND ANALYSIS: Reviewers evaluated the papers separately and independently, rating methodological quality
CD002209. https://doi.org/ of sequence generation, concealment of allocation and bias. Data were extracted independently for meta-analysis and double-
10.1002/14651858.CD002209.pub2
entered.

MAIN RESULTS: Eleven studies met the criteria for inclusion in this review, all were randomized clinical trials, two were double-blind.
There were a total number of 1969 participants. The sequence generation was inadequate in one study, adequate in five studies and
Link to download PDF unclear in the remaining studies. The allocation of concealment was adequate in three studies and unclear in the remaining studies.
Methadone appeared statistically significantly more effective than non-pharmacological approaches in retaining patients in treatment
and in the suppression of heroin use as measured by self report and urine/hair analysis (6 RCTs, RR = 0.66 95% CI 0.56-0.78), but
not statistically different in criminal activity (3 RCTs, RR=0.39; 95%CI: 0.12-1.25) or mortality (4 RCTs, RR=0.48; 95%CI: 0.10-2.39).

Link to Pubmed AUTHORS' CONCLUSIONS: Methadone is an effective maintenance therapy intervention for the treatment of heroin dependence as
it retains patients in treatment and decreases heroin use better than treatments that do not utilize opioid replacement therapy. It
does not show a statistically significant superior effect on criminal activity or mortality.
 Relapse to opioid use disorder after inpatient treatment:

Protective effect of injection naltrexone


 BACKGROUND: Opioid use disorder is often treated with short term hospitalization and medically
supervised withdrawal from opioids followed by counseling alone without medication assisted
treatment (MAT). More evidence is needed to confirm the expectation that the rate of relapse would
be high after short term inpatient treatment and withdrawal from opioids without follow-up MAT.

OBJECTIVE/METHODS: To examine relapse to opioid use disorder in a randomized, multi-site

effectiveness trial of extended-release injection naltrexone (XR-NTX) vs community-based treatment
as usual (TAU) without medication, as a function of the type of clinical service where treatment was
initiated-short-term inpatient (N=59), long-term inpatient (N=48), or outpatient (N=201). Inpatients
typically were admitted to treatment actively using opioids and had completed withdrawal from
opioids before study entry. Outpatients typically presented already abstinent for varying periods of
time.

Nunes, E., Gordon, M., Friedmann, P., Fishman, M.,

RESULTS: One month after randomization, relapse rates on TAU by setting were: short-term inpatient:
Lee, J., Chen, D., Hu, M., Boney, T., Wilson, D.,
O'Brien, C. (2018). Relapse to opioid use disorder
63%; long term inpatient: 14%; outpatient: 28%. On XR-NTX relapse rates after one month were low
after inpatient treatment: Protective effect of injection
naltrexone Journal of Substance Abuse
(<12%) across all three settings. At the end of the 6 month trial, relapse rates on TAU were high
Treatment  85(), 49-55. https://dx.doi.org/10.1016/
j.jsat.2017.04.016
across all treatment-initiation settings (short term inpatient 77%; long term inpatient 59%; outpatient
61%), while XR-NTX exerted a modest protective effect against relapse across settings (short term
inpatient: 59%; long term inpatient 46%; outpatient 38%).

Link to download PDF

CONCLUSIONS: Short term inpatient treatment is associated with a high rate of relapse among
patients with opioid use disorder. These findings support the recommendation that medically
supervised withdrawal from opioids should be followed by medication assisted treatment.

Link to Pubmed
 Opioid agonist treatments and heroin

overdose deaths in Baltimore, Maryland, 1995-2009



OBJECTIVES: We examined the association between the expansion of methadone and
buprenorphine treatment and the prevalence of heroin overdose deaths in Baltimore, Maryland
from 1995 to 2009.

METHODS: We conducted a longitudinal time series analysis of archival data using linear
regression with the Newey-West method to correct SEs for heteroscedasticity and
autocorrelation, adjusting for average heroin purity.

RESULTS: Overdose deaths attributed to heroin ranged from a high of 312 in 1999 to a low of
106 in 2008. While mean heroin purity rose sharply (1995-1999), the increasing number of
patients treated with methadone was not associated with a change in the number of overdose
deaths, but starting in 2000 expansion of opioid agonist treatment was associated with a
Schwartz, R., Gryczynski, J., O’Grady, K., Sharfstein,
J., Warren, G., Olsen, Y., Mitchell, S., Jaffe, J. (2013). decline in overdose deaths. Adjusting for heroin purity and the number of methadone patients,
Opioid Agonist Treatments and Heroin Overdose
Deaths in Baltimore, Maryland, 1995–2009 American there was a statistically significant inverse relationship between heroin overdose deaths and
Journal of Public Health  103(5), 917-922. https://
dx.doi.org/10.2105/ajph.2012.301049 patients treated with buprenorphine (P = .002).

CONCLUSIONS: Increased access to opioid agonist treatment was associated with a

Link to download PDF reduction in heroin overdose deaths. Implementing policies that support evidence-based
medication treatment of opiate dependence may decrease heroin overdose deaths.

Link to Pubmed
 Interim Buprenorphine vs. Waiting List for Opioid Dependence


First Paragraph: Opioid-use disorder has reached epidemic proportions, with high attendant
costs in terms of increases in overdoses and infectious diseases and in economic costs
Despite the demonstrated efficacy of maintaining abstinence by treating patients with opioid
agonists, patients can remain on clinic waiting lists for months, during which time they are at
risk of premature death.2 The use of interim treatment with buprenorphine without formal
counseling while patients remain on waiting lists may mitigate this risk during delays in
treatment.

Sigmon, S., Ochalek, T., Meyer, A., Hruska, B., Heil, S.,
Badger, G., Rose, G., Brooklyn, J., Schwartz, R.,
Moore, B., Higgins, S. (2016). Interim Buprenorphine
vs. Waiting List for Opioid Dependence The New
England Journal of Medicine  375(25), 2504-2505.
https://dx.doi.org/10.1056/nejmc1610047

Link to download PDF

Link to Pubmed
 Mortality risk during and after opioid substitution treatment:
systematic review and meta-analysis of cohort studies

 Objective: To compare the risk for all cause and overdose mortality in people with opioid dependence during and after
substitution treatment with methadone or buprenorphine and to characterize trends in risk of mortality after initiation and
cessation of treatment.

Design: Systematic review and meta-analysis.

Data Sources: Medline, Embase, PsycINFO, and LILACS to September 2016.Study selection Prospective or

retrospective cohort studies in people with opioid dependence that reported deaths from all causes or overdose during
follow-up periods in and out of opioid substitution treatment with methadone or buprenorphine.

Data extraction and synthesis: Two independent reviewers performed data extraction and assessed study quality.
Mortality rates in and out of treatment were jointly combined across methadone or buprenorphine cohorts by using
multivariate random effects meta-analysis.

Results: There were 19 eligible cohorts, following 122 885 people treated with methadone over 1.3-13.9 years and 15 
831 people treated with buprenorphine over 1.1-4.5 years. Pooled all cause mortality rates were 11.3 and 36.1 per 1000
Sordo, L., Barrio, G., Bravo, M., Indave, B., person years in and out of methadone treatment (unadjusted out-to-in rate ratio 3.20, 95% confidence interval 2.65 to
Degenhardt, L., Wiessing, L., Ferri, M., Pastor- 3.86) and reduced to 4.3 and 9.5 in and out of buprenorphine treatment (2.20, 1.34 to 3.61). In pooled trend analysis, all
Barriuso, R. (2017). Mortality risk during and after
opioid substitution treatment: systematic review and cause mortality dropped sharply over the first four weeks of methadone treatment and decreased gradually two weeks
meta-analysis of cohort studies BMJ  357(), j1550.
https://dx.doi.org/10.1136/bmj.j1550
after leaving treatment. All cause mortality remained stable during induction and remaining time on buprenorphine
treatment. Overdose mortality evolved similarly, with pooled overdose mortality rates of 2.6 and 12.7 per 1000 person
years in and out of methadone treatment (unadjusted out-to-in rate ratio 4.80, 2.90 to 7.96) and 1.4 and 4.6 in and out of
buprenorphine treatment.

Link to download PDF

Conclusions: Retention in methadone and buprenorphine treatment is associated with substantial reductions in the risk
for all cause and overdose mortality in people dependent on opioids. The induction phase onto methadone treatment
and the time immediately after leaving treatment with both drugs are periods of particularly increased mortality risk,
which should be dealt with by both public health and clinical strategies to mitigate such risk. These findings are
Link to Pubmed potentially important, but further research must be conducted to properly account for potential confounding and
selection bias in comparisons of mortality risk between opioid substitution treatments, as well as throughout periods in
and out of each treatment.