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The black book of ADHD

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EDUCATIONAL REVIEW
Primary Psychiatry. 2010;17(2):xx-xx

The Black Book of ADHD


David W. Goodman, MD

ABSTRACT
FOCUS POINTS
In 1998, the American Medical Association Scientific Counsel wrote
• Diagnostic accuracy is increased by establishing age of
that attention-deficit/hyperactivity disorder (ADHD) is “one of the onset of symptoms, chronicity of symptom course, present-
best researched disorders in medicine”. Since then, rapidly emerg- ing symptom threshold and impairments, and family his-
tory of attention-deficit/hyperactivity disorder while ruling
ing research coupled with increased interest by clinicians and the out co-existing psychiatric disorders.
public have advanced the identification, diagnosis, and treatment • Diagnostic prioritization facilitates instituting an effective
of ADHD in patients of all ages. In treating patients with ADHD and treatment algorithm.
• Effective pharmacologic treatments take into consider-
their families, we hope that symptoms are reduced throughout the
ation issues of safety, tolerability and adherence.
day leading to improved functioning, enhanced self-confidence,
• Psychotherapeutic approaches are selected for the indi-
and better quality of life for all involved. Because of the volume of vidual needs of the patient and family.
information, there is a need for clinicians to have rapid access to
need to address the issues of the patient in front of you. I
up to date reviews of clinically relevant information to assist in the
hope you find the format useful for the intended purpose and
accurate diagnosis and effective treatment of ADHD and associated we welcome feedback for future editions.
psychiatric comorbidities. For the clinician, satisfaction comes from Attention-deficit/hyperactivity disorder (ADHD) has been
established as a valid psychiatric disorder in children for many
playing an instrumental role in facilitating this optimal outcome.
years. In 1998, the American Medical Association Scientific
This educational review presents information in brief text and Counsel wrote that ADHD is “one of the best researched dis-
tables for quick reference for the busy practitioner. orders in medicine”.1 The explosion of neuroimaging research
in the past 10 years has demonstrated clear differences in the
ADHD brain from dopamine receptor density in the basal
ganglion2 to morphologic differences in white matter,3 basal
INTRODUCTION ganglion,4 and cerebellum5 to rate differences in the neurode-
“The Black Book of Attention-Deficit/Hyperactivity velopment of the frontal cortex.4,6 Heritability of 76% has been
Disorder” is a concise presentation of rapidly accessible infor- established with family, twin, and adoption studies.7 With a
mation important to clinicians diagnosing and treating these growing number of prospective longitudinal studies of ADHD
patients and their families. I have attempted to cull through children followed 10–20 years into adulthood,8 we have come
the literature and present clinically relevant information in to understand that up to 65% of these children will continue to
text and table format so that you can quickly find what you have persistent and impairing ADHD symptoms. From these

Dr. Goodman is Director of the Adult Attention Deficit Disorder Center of Maryland, and Assistant Professor in the Department of Psychiatry and Behavioral Sciences at Johns Hopkins School of
Medicine in Baltimore.
Disclosure: Dr. Goodman is a consultant to Avacat, Clinical Global Advisors, Eli Lilly, Forest Laboratories, JK Associates, McNeil, Medscape, New River Pharmaceuticals, Novartis, Schering-Plough,
Shire, Thompson Reuters, and WebMD; is on the speaker’s bureaus of Forest Laboratories, McNeil, Shire, and Wyeth; has received research grants from Cephalon, Eli Lilly, Excerpta Medicine, Forest
Laboratories, McNeil, New River Pharmaceuticals, and Shire; has received honoraria from Eli Lilly, Elsevier, Forest Laboratories, JK Associates, McNeil, Medscape, Shire, Synmed, Veritas Institue,
WebMD, and Wyeth; and receives royalties from MBL Communications.
Please direct all correspondence to: David W. Goodman, MD, Assistant Professor, Johns Hopkins Univ School of Medicine, Dept of Psychiatry and Behavioral Sciences, Johns Hopkins at Green Spring
Station, 10751 Falls Road, St 306, Baltimore, MD 21093; Tel: 410-583-2723; E-mail: [email protected].

Primary Psychiatry 33 February 2010


D.W. Goodman

findings and epidemiologic data, the prevalence of ADHD presentation of ADHD across the life span. This means that
in children is 7.8% (4.5 million)9 and 4.4% (9–10 million)11 symptom descriptions will need to be age congruent and the
in adults in the United States. Of the children with ADHD, threshold number of symptoms will be reconsidered. The age
<60% have been treated in the past year while only <15% of of onset before 7 years of age is likely to be increased because
the ADHD adults have been treated in the past year.10 individuals with inattentive type are typically diagnosed
The criteria for diagnosing ADHD and its subtypes are after 7 years of age.13 However, remember that ADHD is a
enumerated by the Diagnostic and Statistical Manual of Mental childhood disorder that may persist into adulthood so the
Disorders, Fourth Edition, Text Revision.11 The original symp- age of onset needs to be set in childhood/early adolescence.
tom criteria were field tested in children 5–17 years of age12 The criteria of impairment in >2 domains is likely to remain
and not in older patients with ADHD. Therefore, when diag- because this is a disorder that impacts multiple domains of
nosing adults, clinicians and researchers have had to extrapolate life. However, the degree of impairment and the domains
the symptoms that appear at older ages. This clinical extrapola- may require greater clarification because adaptive skills, IQ,
tion has been aided by following children with ADHD into and environmental structure may alter the appearance of
adolescence and adulthood to see which symptoms persist impairments.11 The work to be done for the forthcoming
with impairment and which subside. With age, some patients DSM-V will greatly broaden and enhance our ability to iden-
develop compensatory skills to limit the interference they expe- tify ADHD accurately in all age groups.
rience from their symptoms. Although impairments may not This educational review has been divided into specific topics.
appear evident, these patients are often working harder daily to “Neurobiology” reviews the epidemiology of child and adults
achieve what someone else achieves with little effort. with ADHD in the US and internationally, and a review of
As individuals with ADHD ages, life presents ever-changing neuroimaging findings. “Diagnosis” presents the diagnostic
demands often requiring a greater ability to remember and criteria in the DSM-IV-TR; a review of extrapolated diagnostic
organize daily tasks. Children with ADHD not diagnosed in criteria for adults; a list of ADHD rating scales for children,
childhood because they did not present with disruptive behav- adolescents, and adults, and defines and reviews executive
ior or severe academic decline may face challenges later in life dysfunction and functional impact of ADHD. “Treatment
as the demands of adulthood exceed their ability to compen- Guidelines” reviews the current ADHD treatment guidelines
sate. It is at this time they may present to clinicians with com- for child, adolescent, and adults with ADHD established
plaints of frustration, demoralization, anxiety, and depression. by the current meta-analyses of research findings; treatment
Given the high prevalence rate in children and adults relative algorithms for pure ADHD and ADHD with co-existing psy-
to other psychiatric disorders, an ADHD assessment should chiatric comorbidities. “Treatment Options” provides a list of
be included in every initial mental health evaluation. medications available and approved by the US Food and Drug
In recent years, research has focused on the concurrent Administration, a list of stimulant delivery vehicles, distin-
psychiatric comorbidities that can complicate the diagnos- guishing efficacy from effectiveness of treatments, a review of
tic process. In children, oppositional defiant disorder and complementary treatments and research findings in controlled
conduct disorder were commonly understood and identi- studies, a review of current safety considerations and side
fied. With emerging research, anxiety and mood disorders effects for ADHD medications in age specific populations, and
in children with ADHD have necessitated greater clinical a review of psychotherapies employed.
acumen for accurate diagnoses. The same diagnostic com- The rapidly emerging research coupled with increased interest
plexities are introduced in older patients with ADHD. The by clinicians and the public at large will advance the diagnosis
onset of substance abuse, major depression, bipolar disorder, and treatment of ADHD in patients of all ages. We hope that
and anxiety disorders add a new dimension to developing a in treating patients with ADHD and their families symptoms
treatment algorithm in the presence of ADHD. Diagnostic are reduced throughout the day leading to improved function-
prioritization of multiple concurrent disorders is necessary ing, enhanced self-confidence, and better quality of life for all
to construct a treatment algorithm. The goal is to effectively involved. For you, the clinician, satisfaction comes from playing
treat one disorder without worsening the other disorders. For an instrumental role in facilitating this optimal outcome. I hope
children and adolescents, the American Academy of Child this article provides you with the assistance to achieve this goal.
and Adolescent Psychiatry guidelines lay out a systematic
approach to the treatment of ADHD and co-existing disor-
ders. For adults, there are no such guidelines established. CONCLUSION
Because of our understanding of ADHD as a potentially
life-long disorder, the American Psychiatric Association com- With decades of research on childhood ADHD, the validity
mittee working on diagnostic revisions for the forthcom- of the disorder is well substantiated. Although adult ADHD
ing DSM-V will consider the research accumulating on the was presented in psychiatric literature in the mid-1970s, the

Primary Psychiatry 34 February 2010


The Black Book of ADHD

emerging body of literature on ADHD across the lifespan has by the FDA and physicians need to be knowledgeable about
exploded in the last 52 decades. New technologies have allowed assessing medical risk factors in patients. With the treatment
science to investigate genetic markers. Neuro-imaging has of adults versus children, physicians have new considerations
facilitated a better understanding of developmental, structural, in treatment like pregnancy, substance abuse, and poly-phar-
molecular, and functional difference in the brains of children maceutical treatment of concurrent medical conditions (ie, car-
and adults with ADHD. Longitudinal studies have verified diovascular disease, diabetes, hypertension, pain syndromes).
that 1 in 2 children with ADHD will continue to have impair- Patients often use complementary and alternative treatments
ing symptoms into adulthood. The negative consequences of without substantial controlled trial efficacy. The concep-
untreated ADHD have been enumerated across the lifespan of tual distinction between efficacy and effectiveness will become
patients with ADHD. High rates of psychiatric comorbidities increasingly relevant as treatment comparative trials look at the
add complexity to the diagnostic assessment and prioritization economics of treatment.
in order to formulate a thoughtful treatment algorithm. The Because formal training in ADHD is highly variable and vir-
psychiatric literature is extensive for clinical guidance when tually absent for adult ADHD, many physicians find they need
treating children; however there remains a paucity of adult stud- to learn about this disorder in clinical practice. Summarizing
ies that offer clinical guidance for the treatment of adults with this literature into clinically relevant and rapidly accessible
ADHD and co-existing psychiatric disorders. information is critical to facilitating this educational pursuit.
Efficacy trials for children have clearly demonstrated the This article presents a portion of the tables and text from the
benefits of medication and behavioral psychotherapies tailored book, in which you will find additional tables and informa-
to the specific symptoms and needs of the child and family. tion on rating scales, child treatment algorithms for comorbid
Although limited, a growing body of efficacy trials in adult disorders, and elaboration of Americans with Disabilities Act
ADHD over the past 20 years also demonstrates the benefit and Individual Education Plan criteria. This educational review
of medications and specific therapies. The specific approval presents the distillation of literature into clinical topics, and is
of medications by the FDA in the past 7 years to treat adults written in table format for a fast read. The unique format of
with ADHD helps encourage the identification and treatment this article and its presentation of up-to-date clinically relevant
of these patients. Advances in medication delivery systems information makes it a useful addition to the library of clini-
have introduced different mechanisms in order to extend the cians caring for ADHD patients and their families. PP
duration of action. Safety issues have been recently highlighted

TABLE 1 TABLE 2
PREVALENCE OF ADHD BY AGE 9,10,25-33 FUNCTIONAL AND DEVELOPMENTAL DIFFERENCES IN ADHD
BRAINS3,6,42,43
Child 8.7% United States25 6.7% United States26
7.8% United States9 Imaging
Neuroanatomy Technique Findings
Adolescent 16.4% China 28
8.5% Finland 27

Differences in dopamine PET Reduced dopamine activity in


Adult 4.4% United States10 2.8% Italy29 activity in caudate and response to MPH given intrave-
limbic regions nously
7.3% France29 1.9% Colombia29
5.2% United States 29
1.9% Mexico29 Neurodevelopmental MRI 2-year delay in cortical thickening
trajectory in medial and superior prefrontal
5.0% Netherlands29 1.8% Lebanon29 and precentral regions
4.1% Belgium 29
1.2% Spain29 Differences in activa- fMRI Activation of bitemporal regions
tion of neural networks (controls activate dorsal anterior
3.1% Germany 29
for tasks cingulate gyrus)
Persistence of ADHD from Childhood to Adulthood Although neuroimaging research has been able to show multiple differences in ADHD
brains versus controls (both children and adults), these results have not yet demonstrated
• 60% to 85% childhood into teen years30-32
their utility in the clinical setting. At present, there is no support to use neuroimaging for
• 46% by parent report; childhood into adulthood33 diagnosis or treatment selection for ADHD in any age group.
• 49% to 54% using a developmental definition (<93rd percentile on symp- PET=positron emmision tomography; MPH=methylphenidate; MRI=magnetic resonance
toms relative to age-matched controls) of the disorder33 imaging; fMRI=functional magnetic resonance imaging.
Goodman DW. Primary Psychiatry. Vol 17, No 2. 2010. Goodman DW. Primary Psychiatry. Vol 17, No 2. 2010.

Primary Psychiatry 35 February 2010


D.W. Goodman

TABLE 3 TABLE 4
DSM-IV CRITERIA FOR ADHD 11
EXECUTIVE FUNCTION70 AND DYSFUNCTION71
I. Either A or B Executive Functions Description
A. At least six of the following symptoms of inattention have been present for at Set shifting Changing activity or solution strategy (instead of
least 6 months to an extent that is disruptive and inappropriate for develop- doing something the same way over and over)
mental level:
Planning/organizing Managing current and future tasks
• Often does not give close attention to details or makes careless mistakes in
work or other activities Working memory Holding and manipulating information in one’s
• Often has trouble keeping attention on tasks or play activities mind
• Often does not seem to listen when spoken to directly Inhibition Holding back from initial responses (ie, withhold-
• Often does not follow instructions and fails to finish duties in the workplace ing judgment or doing what is expected rather than
(not due to oppositional behavior or failure to understand instructions) what one wants)
• Often has trouble organizing activities Initiation Ability to get started (even on an undesirable task)
• Often avoids, dislikes, or does not want to do things that take a lot of mental Task monitoring Keeping track of behavior
effort for a long period of time
Rates of Executive Dysfunction in Children
• Often loses things needed for tasks and activities
and Adults With and Without ADHD
• Is often easily distracted
Non-
• Is often forgetful in daily activities ADHD
B. At least six of the following symptoms of hyperactivity-impulsivity have been ADHD+EF* Controls† Outcomes vs. Controls
present for at least 6 months to an extent that is disruptive and inappropriate Child 33% 12% ADHD+EF: Higher risk of grade reten-
for developmental level:
tion, LDs, lower academic achievement
Hyperactivity
Adult 31% 16% ADHD+EF: Lower levels of education,
• Often fidgets or squirms in seat occupation and overall SES
• Often gets up from seat when remaining in seat is expected * Defined by 1.5 SD from mean of controls on more than two executive function measures.
• Often feels very restless (Adjusted for gender, age, IQ, LD, and SES).
• Often has trouble enjoying leisure activities quietly † Did not meet DSM-IV criteria for ADHD
• Is often “on the go” or often acts as if “driven by a motor” EF=executive function; LD=learning disability; SES=social economic status; DSM-
• Often talks excessively IV=Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition.

Impulsivity Goodman DW. Primary Psychiatry. Vol 17, No 2. 2010.


• Often blurts out answers before questions have been finished
• Often has trouble waiting one’s turn
• Often interrupts or intrudes on others
II. Some symptoms that cause impairment were present before 7 years of age
III. Some impairment from the symptoms is present in two or more settings
(eg, at school, work, and at home)
V. The symptoms do not happen only during the course of a pervasive develop-
mental disorder, schizophrenia, or other psychotic disorder, and the symptoms
are not better accounted for by another mental disorder
Based on these criteria, three subtypes of ADHD are identified:
• ADHD, combined type: if both criteria 1A and 1B are met for the previous 6
months
• ADHD, predominantly inattentive type: if criterion 1A is met but criterion 1B
is not met for the previous 6 months
• ADHD, predominantly hyperactive-impulsive type: if criterion 1B is met but
criterion 1A is not met for the previous 6 months
ADHD-residual type: diagnostic criteria achieved in childhood, however current symptoms
do not reach diagnostic threshold criteria

ADHD-not otherwise specified: current symptoms reach diagnostic symptom threshold,


however diagnostic threshold criteria were not reach in childhood
Goodman DW. Primary Psychiatry. Vol 17, No 2. 2010.

Primary Psychiatry 36 February 2010


The Black Book of ADHD

TABLE 5
FUNCTIONAL IMPACTS OF ADHD
Children/Adolescents Adults82,88-91
Accidents/Injuries Education
• Higher risk of bicycle/pedestrian injury, head injury, multiple injuries, • Less likely to finish college89
admissions to ICU72
• Lower educational attainment than patient IQ would predict92
Educational
Marital/Social/Sex
• Higher rates of grade retention8
• 4x higher risk to contract an STD81
• 8x higher risk for school expulsion or dropout73
• Nearly 2x higher risk of divorce/separation89
• Higher rates of associated learning disabilities8
• Less satisfied with social relationships89
• Lower rates of high school or college completion89
• Poorer relationship with their parents89
Social Substance/Alcohol/Tobacco
• Lack of friendships74 • 2x to 3x higher rates of substance abuse disorder10,93
• Less well liked by peers compared to non-ADHD peers75 • 2x to 3x higher rates of cigarette smoking94
• Difficulty retaining peer status76-78 • Severity of ADHD symptoms associated with increased use of tobacco,
Substance/Alcohol/Tobacco marijuana, and alcohol into adulthood95
• 2x higher risk for tobacco smoking79,80 Occupational/Workplace82,88-91
• 2.5x higher risk for alcohol abuse • More likely to be fired from or quit a job impulsively
• 2x higher risk for substance abuse 80 • Receive a lower salary89
Sexual Activity • Have poorer work performance scores
• 4x more likely to have contracted an STD 78 • More likely to have more frequent job changes over 10 years89
• 10x higher risk for unplanned pregnancy8 • 3x more likely to be currently unemployed89
• Higher risk for STDs and multiple partners 81 • Lower occupational attainment than patient IQ would predict92
Driving Legal
• 2x to 6x higher rates of suspended or revoked driver’s license, more • 2x more likely to have been arrested89
traffic violations and speeding tickets, more motor vehicle accidents, • 3x more likely to be convicted96
and greater vehicular damage82-86
• 15x more likely to be incarcerated96
Medical costs
• Greater tendency toward antisocial/criminal behavior89
• 9 year median cost per person: $4,306 (ADHD) versus $1,944 (non-
ADHD)87 Financial
• Household income significantly lower than controls90
Medical Costs
• Higher accident claims and significantly higher cost/accident: $483
(ADHD) versus $146 (controls)97
• Family members of individuals with ADHD has 1.6 times more medical
claims versus controls98
Many of the differences are compared to age-matched controls and are statistically significant.
ICU=intensive care unit; STD=sexually transmitted disease.

Primary Psychiatry 37 February 2010


D.W. Goodman

TABLE 6 TABLE 7
ADHD AND COMORBIDITIES BY AGE GROUP CLINICAL QUESTIONS USED IN THE ASSESSMENT OF
The Preschoolers with ADHD Treatment Study (PATS)99
CARDIOVASCULAR RISK IN CHILDREN AND ADOLESCENTS WITH
(n=302; 3–6 years of age) ADHD103-105
ADHD alone 30.4% American Academy of Pediatrics recommendations (2008):
ADHD plus oppositional defiant disorder 52.3% 1. The AAP continues to recommend a careful assessment of all children,
including those starting stimulants, using a targeted cardiac history and a
ADHD plus communication disorder 21.9% physical examination, including a careful cardiac examination.
ADHD plus anxiety 12.3% 2. Given current evidence, the AAP encourages primary care and sub-
ADHD plus other comorbidities 4.3% specialty physicians to continue currently recommended treatment
for ADHD, including stimulant medications, without obtaining routine
Multi-modal Treatment Study (MTS)100
ECGs or routine subspecialty cardiology evaluations for most children
(n=579; 7–10 years of age)
before starting therapy with these medications.
ADHD alone 31% Patient history:
ADHD plus oppositional defiant disorder 40% 1. History of fainting or dizziness (particularly with exercise)
ADHD plus anxiety disorder 34% 2. Chest pain or shortness of breath with exercise
ADHD plus conduct disorder 14% 3. Unexplained, noticeable change in exercise tolerance
ADHD plus tic disorder 11% 4. Palpitations, increased heart rate, or extra or skipped heart beats
ADHD plus mood disorder 4% 5. History of heart murmur other than innocent or functional murmur or
National Comorbidity Survey Replication (NCSR)10 history of other heart problems

(n=3,199; 18–44 years of age) 6. Intercurrent viral illness with chest pains or palpitations
7. Rheumatic fever
ADHD plus mood disorder (total)
38.3% 8. History of high blood pressure
Bipolar disorder
19.4% 9. Seizures
Major depression
18.6% 10. Current medications (prescribed and over the counter)
Chronic dysthmia
12.8% 11. Health supplements (herbal, vitamins, sports drinks, etc)
ADHD plus anxiety disorder (total)
47% Family history:
Social phobia
29.3% 1. Sudden cardiac death or heart attack in members <35 years of age
Posttraumatic stress disorder
11.9% 2. Sudden or unexplained death in someone young
Panic disorder
8.9% 3. Sudden death during exercise
Generalized anxiety disorder
8.0% 4. Cardiac arrhythmias
Agoraphobia
4.0% 5. Hypertrophic cardiomyopathy or other cardiomyopathy, including
Obsessive-compulsive disorder dilated cardiomyopathy and right vertricular cardiomyopathy (right
2.7%
ADHD plus substance use disorder ventricular dysplasia)
15.2%
6. Long-QT syndrome, short QT syndrome, or Brugada syndrome
Goodman DW. Primary Psychiatry. Vol 17, No 2. 2010. 7. Wolff-Parkinson-White syndrome or similar abnormal rhythm
conditions
8. Event requiring resuscitation in young members (<35 years of age),
including syncope requiring resuscitation
9. Marfan syndrome
AAP=American Academy of Pedicatrics; ECGs=electrocardiograms.

Goodman DW. Primary Psychiatry. Vol 17, No 2. 2010.

Primary Psychiatry 38 February 2010


The Black Book of ADHD

FIGURE 1
PHARMACOLOGIC TREATMENT OF CHILDHOOD ADHD WITH NO SIGNIFICANT COMORBID DISORDERS*57

DiagnosticDiagnostic
AssessmantAssessmant
and and
Stage 0 Stage 0 Family Consultation
Family Consultation
RegardingRegarding
TreatmentTreatment
Alternatives
Alternatives
Any stage(s)
Anycan
stage(s)
be skipped
can be skipped Non-Medical
Non-Medical
depending depending
on the clinical
on the
picture
clinical picture TreatmentTreatment
Alternatives
Alternatives
Stage 1 Stage 1 Methylphenidate
Methylphenidate
or Amphetamine
or Amphetamine
Response Response
Partial Partial Stage 1A Stage 1A
Response Response (Optional) (Optional)
(if MPH or AMPH
(if MPH or AMPH AMP formulation Response Response
AMP formulation
not used in stage
not used
1 in stage 1 Continuation
Continuation
used in Stage
used1) in Stage 1)
Partial Response
Partial Response
or Nonresponse
or Nonresponse Partial Response
Partial Response
Stage 2 Stage 2 Stimulant Stimulant
not used innot
Stage
used1in Stage 1 or Nonresponse
or Nonresponse
Response Response
Partial Partial Stage 2A Stage 2A
Response Response (Optional) (Optional)
(if MPH or AMPH
(if MPH or AMPH AMP formulation
Response Response
AMP formulation
not used in stage
not used
2 in stage 2 Continuation
Continuation
used in Stage
used2) in Stage 2)
Partial Response
Partial Response
or Nonresponse
or Nonresponse Partial Response
Partial Response
or Nonresponse
or Nonresponse
Stage 3 Stage 3 Atomoxetine
Atomoxetine
Response Response
Stage 3A Stage 3A
Partial Partial (Optional) (Optional)
Response Response Combine stimulant Response Response
Combine stimulant
and atomoxetine
and atomoxetine Continuation
Continuation
to stimulantto stimulant
Partial Response
Partial Response
or atomoxetine
or atomoxetine
or Nonresponse
or Nonresponse Partial Response
Partial Response
Stage 4 Stage 4 BupropionBupropion
or TCA or TCA or Nonresponse
or Nonresponse
Response Response
Partial Response
Partial Response Continuation
Continuation
or Nonresponse
or Nonresponse
Stage 5 Stage 5 Agent not Agent
used innot
Stage
used4in Stage 4
Response Response
Partial Response
Partial Response Continuation
Continuation
or Nonresponse
or Nonresponse
Stage 6 Stage 6 Alpha Agonist
Alpha Agonist

Clinical Clinical Maintenance


Maintenance
Consultation
Consultation

* The algorithm predates the FDA approval of guanfacine ER in September 2009. With this approval, the sequence of medication trials should be the use of approved
medications before the off-label use of alternative medications. The algorithm offers the sequence of monotherapeutic medication trials and has not considered
polypharmaceutical treatment in child/adolescent ADHD.
MPH=methylamphetamine; AMP=amphetamine; TCA=tricyclic antidepressant; FDA=Food and Drug Administration; ER=extended release.
Goodman DW. Primary Psychiatry. Vol 17, No 2. 2010.

Primary Psychiatry 39 February 2010


D.W. Goodman

TABLE 8
EFFICACY VS. EFFECTIVENESS
Efficacy Effectiveness
Purpose Determine treatment effect; submission to the FDA for Care of patient and treatment of disorder/disease
disorder treatment indication
Setting Clinical trial, research center Naturalistic, community setting
Subject Population Recruited subjects Referred patients
Inclusion Criteria Specific diagnostic criteria by interview/screen General clinical diagnostic impression for disorder/disease
Exclusion Criteria No or limited comorbidities (medical or psychiatric) Comorbidities included (medical or psychiatric) leading to greater clinical consid-
erations
Study/Treatment Design Single treatment without confounding variables Treatment may be delivered with confounding variables (ie, other medications or
concurrent disorders)
Subject Motivation High due to study compensation and free service Moderate because of treatment cost and perceived risk:benefit
Adverse Events Spontaneous report by subjects; potential for underreporting Specific side-effect questions; potential for more accurate assessment or over-
reporting
Tolerance of Higher due to study compensation and motivation to partici- Low due to concern about side effects and medication cost
Adverse Events pate in a study
Statistic Measure P value (<.05) (The event did not occur by chance) Effect size (measures the magnitude of difference between active agent and com-
parator/placebo)
Compliance High due to study compensation, free service, and participa- Moderate due to medication cost and risk, expectation of benefit
tion in a study
Outcome Optimized by dosing, a diagnostic specific, and motivated Possibly compromised by co-existing factors
subject population
As a clinician, it is important to understand two concepts that determine the benefits of treatments: efficacy and effectiveness. Efficacy and effectiveness are concepts to evaluate the
degree of benefit a treatment offers a disorder/disease. However, the settings under which these conclusions are reached are very different. Trials for drug efficacy follow set guidelines
that use recruited subjects who usually have no comorbidities so as to determine whether a treatment clearly works for a specific disorder/disease. Although efficacy is determined by
this methodology, the clinicians often find that research subjects are infrequently the patients seen in clinical practice. Therefore, the outcome of the treatment in a practice setting
may not be similar to the research outcome because of several confounding factors not considered during the research trial. For the clinician, understanding these differences allows
for a clearer translation of clinical research findings into clinical practice. The Table enumerates the differences between efficacy and effectiveness.
FDA=Food and Drug Administration.
Goodman DW. Primary Psychiatry. Vol 17, No 2. 2010.

TABLE 9
ADHD MEDICATION APPROVAL DATES BY THE FDA FOR ADOLESCENTS AND ADULTS110
Drug Active Constituent FDA Approval Date Drug Active Constituent FDA Approval Date

ADHD medications approved by the FDA for the treatment of ADHD in ADHD medications approved by the FDA for the treatment of ADHD in
adolescents adults

Adderall Mixed amphetamine salts 2/13/1996 Strattera Atomoxetine 11/26/2002

Concerta Methylphenidate 8/1/2000 Adderall XR Mixed amphetamine salts 8/14/2004

Methylin ER Methylphenidate 9/5/2000 Focalin XR Dexmethylphenidate 6/13/2005

Metadate CD Methylphenidate 4/3/2001 Vyvanse Lisdexamfetamine 4/24/2008

Adderall XR Mixed amphetamine salts 11/10/2001 Concerta Methylphenidate 6/28/2008

Focalin Dexmethylphenidate 11/13/2001 No short-acting stimulant medication is approved by the FDA for the treatment of adults
with ADHD.
Ritalin LA Methylphenidate 6/5/2002
Strattera Atomoxetine 11/26/2002
Methylin chewable Methylphenidate 4/15/2003
Focalin XR Dexmethylphenidate 5/26/2005

Goodman DW. Primary Psychiatry. Vol 17, No 2. 2010.

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The Black Book of ADHD

TABLE 10
MEDICATIONS APPROVED BY THE FDA FOR ADHD34,58
Brand Name Typical FDA Off-Label
(Manufacturer) Dose Form Starting Dose Max/Daily Max/Day Comments
α2 agonist
Intuniv (Shire) 1, 2, 3, 4 mg tablets 1 mg 4 mg Not yet known Not a scheduled II medication. Consider in ADHD medica-
tion sensitive children, adjunct treatment, or concurrent
tics; monitor for somnolence, headache, fatigue, GI upset,
decreased BP, dizziness
Amphetamine Preparations
Short-acting Short-acting stimulants often used as initial treatment
in small children (<16 kg), but have disadvantage of
Adderall* (Shire) 5, 7.5, 10, 12.5, 15, 3–5 years: 2.5 mg QD; 40 mg >50 kg: 60 mg BID-TID. Dosing to control symptoms throughout day.
20, 30 mg tablets ≥6 years: 5 mg QD-BID Once-daily, long-acting stimulants are now recom-
mended as first line medication
Dexedrine* 5 mg capsules 3–5 years: 2.5 mg QD 40 mg >50 kg: 60 mg
(GlaxoSmithKline)
DextroStat (Shire) 5, 10 mg capsules ≥6 years of age: 60 mg >50 kg: 60 mg
5 mg QD-BID
Long-acting Longer acting stimulants offer greater convenience,
confidentiality, and compliance with single daily dosing
Adderall XR* (Shire) 5, 10, 15, 20, 25, 30 ≥6 years: 10 mg QD 30 mg >50 kg: 60 mg but may have greater problematic effects on daytime
mg capsules appetite and sleep; all three medications may be opened
and sprinkled on soft foods
Dexedrine spansule 5, 10, 15 mg capsules ≥6 years: 5–10 mg 40 mg >50 kg: 60 mg
(GlaxoSmithKline) QD-BID
Vyvanse (Shire) 20, 30, 40, 50, 60, 70 30 mg QD 70 mg Not yet determined
mg capsules
Methylphenidate Preparations
Short-acting Short-acting stimulants often used as initial treatment
in small children (<16 kg) but have disadvantage
Focalin (Novartis) 2.5, 5, 10 mg capsules 2.5 mg BID 20 mg 50 mg of BID-TID. dosing to control symptoms throughout
day. Once-daily long-acting stimulants are now recom-
Methylin* 5, 10, 20 mg tablets 5 mg BID 60 mg >50 kg: 100 mg mended as first line medication
(Mallinckrodt Pharma)
Ritalin* (Novartis) 5, 10, 20 mg 5 mg BID 60 mg >50 kg: 100 mg
Intermediate-acting
Longer acting stimulants offer greater convenience,
Metadate ER 10, 20 mg capsules 10 mg QAM 60 mg >50 kg: 100 mg confidentiality, and compliance with single daily dosing
(UCB Pharma) but may have greater problematic effects on daytime
appetite and sleep
Methylin ER 10, 20 mg capsules 10 mg QAM 60 mg >50 kg: 100 mg
(Mallinckrodt Pharm)
Ritalin SR* (Novartis) 20 mg 10 mg QAM 60 mg >50 kg: 100 mg
Metadate CD 10, 20, 30, 40, 50, 20 mg QAM 60 mg >50 kg: 100 mg Metadate CD and Ritalin LA caps may be opened and
(UCB Pharma) 60 mg sprinkled on soft food
Ritalin LA (Novartis) 10, 20, 30, 40 mg 20 mg QAM 60 mg >50 kg: 100 mg
Long-acting
Concerta (McNeil) 18, 27, 36, 54 mg 18 mg QAM 72 mg 108 mg Swallow whole with liquids; nonabsorbable tablet shell
capsules may be seen in stool.
Daytrana patch (Shire) 10, 15, 20, 30 mg Begin with 10 mg patch 30 mg Not yet known Recommended wear-time is 9 hours resulting in 12 duration
patches QD, then titrate up by of action. Daily placement by alternating hips. Erythematous
patch strength rash may limit use
Focalin XR (Novartis) 5, 10, 15, and 20 mg 5 mg QAM 30 mg 50 mg Can be sprinkled on soft food
capsules
Selective Norepinephrine Reuptake Inhibitor
Strattera (Eli Lilly) 10, 18, 25, 40, 60, 80, Children and adolescents Lesser of 1.4 Lesser of 1.8 Not a schedule II medication
and 100 mg capsules <70 kg: 0.5 mg/kg/day mg/kg or 100 mg/kg or 100 mg;
for 4 days; then 1 mg/kg/ mg; adult adult trials to Consider if active substance abuse or severe side effects
day for 4 days; then 1.2 therapeutic 120 mg of stimulant intolerance (mood lability, tics); give QAM or
mg/kg/day; adult starting dose: 80– divided doses BID; do not open capsule; monitor closely
dose: 40 mg/day 100 mg/day for suicidal thinking and behavior, clinical worsening, or
* Generic formulation available unusual changes in behavior

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D.W. Goodman

TABLE 11
MEDICATIONS USED FOR ADHD THAT ARE NOT APPROVED BY THE FDA FOR ADHD34,58
Generic Class/
Brand Name Dose Form Typical Starting Dose Maximum Per Day Comments (by compound)
Antidepressants
Bupropion Lowers seizure threshold; contraindicated
75, 100 mg Lesser of 3 mg/kg/day or Lesser of 6 mg/kg or 300 mg, if current seizure disorder. Bupropion low-
Wellbutrin* (GSK, tablets 150 mg/day with no single dose >150 mg ers seizure threshold; the extended release
Teva) preparations lower the risk; contraindicated
Wellbutrin SR* (GSK, 100, 150, 200 150 mg 450 mg in adults if current seizure disorder
Allscripts) mg tablets Usually given in divided doses, BID for chil-
Wellbutrin XL* (GSK, 150, 300 mg 150 mg 450 mg in adults dren, TID for adolescents, for both safety and
Pharma PAC) tablets effectiveness. In children and adolescents,
the dosing is BID for all preparations
In adults, bupropion is dosed BID, while SR
and XL are dosed QAM to 300 mg; and split
dose at 450 mg QD
Imipramine In children and adolescents, obtain base-
line ECG before starting imipramine and
Tofranil* (Mallinkrt 10, 25, 50, 75 1 mg/kg/day Lesser of 4 mg/kg or 200 mg nortriptyline
Pharm, Sandoz) mg tablets
Nortriptyline In children and adolescents, obtain base-
10, 25, 50, line ECG before starting imipramine and
Pamelor,* (Sandoz, 75 mg 0.5 mg/kg/day Lesser of 2 mg/kg or 100 mg nortriptyline
Mallinkrt Pharm); capsules
Aventyl* (Eli Lilly)
α2-Adrenergic agonists May be used alone or as adjuvant to another
medication for ADHD
Clonidine Effective for impulsivity and hyperactiv-
ity; tics worsening from stimulants; sleep
Catapres* (Boerhinger 0.1, 0.2, 0.3 <45 kg: 0.05 mg QHS; titrate in 27–40.5 kg: 0.2 mg;
disturbances
Ingelheim; Physicians mg tablets 0.05-mg increments BID, TID, QID; 40.5–45 kg: 0.3 mg;
TC) >45 kg: 0.1 mg QHS; titrate in 0.1- >45 kg: 0.4 mg Taper off to avoid rebound hypertension
mg increments BID, TID, QID
Guanfacine Effective for impulsivity and hyperactivity;
tics worsening from stimulants
Tenex* (ESP Pharma) 1, 2 mg 45 kg: 0.5 mg QHS; titrate in 0.5-mg 27–40.5 kg: 2 mg;
tablets increments BID, TID, QID; > 45 kg: 1 40.5–45 kg: 3 mg; Taper off to avoid rebound hypertension
mg QHS; titrate in 1-mg increments >45 kg: 4 mg
BID, TID, QID

* Generic formulation available.


GSK=GlaxoSmithKline; SR=sustained release; XL=extended release; ECG=electrocardiogram.
Goodman DW. Primary Psychiatry. Vol 17, No 2. 2010.

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The Black Book of ADHD

TABLE 12
STIMULANT PREPARATIONS DELIVERY SYSTEMS
Duration of Action
Preparation Stimulant Description for Children
Liquid Methylphenidate (Methylin), dextroamphetamine Liquid, immediate delivery 3–4 hours
(Liquadd)
Immediate Methylphenidate (Ritalin, Metadate, No delivery system; immediate delivery 3–4 hours

Shortest
release tablet Methylin), dexmethylphenidate (Focalin), dextro-
amphetamine (Dexedrine), mixed amphetamine
salts (Adderall)
Chewable Methylphenidate (chewable Methylin) No delivery system; immediate delivery 3–4 hours
tablet
Slow Methylphenidate SR (Ritalin SR) Wax matrix 4–6 hours
Release Matrix

Potential Duration
Beaded* Mixed-amphetamine salts XR (Adderall XR); meth- Double-beaded; immediate-release bead followed Up to 12 hours
ylphenidate (Metadate CD); by 2nd release 4 hours later; ph-dependent polymer
dextro-amphetamine (Dexedrine spansules)
SODAS* Dexmethylphenidate XR (Focalin XR), methylphe- SODAS® (Spheroidal Oral Drug Absorption System); Up to 12 hours
nidate LA (Ritalin LA) immediate release bead then 2nd release bead later
OROS Methylphenidate OROS (Concerta) OROS® (Oral Release Osomotic System; osmotic Up to 12 hours
push devise delivers MPH with an ascending phar-
macokinetic profile over 8 hours
Patch Methylphenidate patch (Daytrana) DOT® (Delivery Optimized Thermodynamics) Matrix Variable depending
transdermal system; cutaneous gradient diffusion on wear time; 12
hours with 9-hour

Longest
wear time
Prodrug† Lisdexamfetamine (Vyvanse) No delivery system; duration of action determined Up to 13 hours
by enzymatic hydrolysis of lysine from dextroam-
phetamine

The preparation (vehicle of delivery) determines the rate of absorption of the stimulant into the circulation and this determines the duration of action of the medication. The half-life
of the compound always remains the same regardless of the vehicle of delivery as it is established once the compound is metabolized in the blood circulation. Adverse events may be
related to the compound and/or the preparation. Side effect intolerance to one preparation may not predict sensitivity to another preparation of the same compound. Given the broad
range of available preparations, clinicians should be able to find an appropriate choice for their patient.
* Can be sprinkled on soft food
† Can be dissolved in water; duration of action remains the same
SR=sustained release; ER=extended release; CD=; LA=long-acting.
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D.W. Goodman

TABLE 13 TABLE 14
CYP INHIBITORY EFFECTS OF ADHD MEDICATIONS113 PREGNANCY AND ADHD MEDICATIONS114-118
Medication 1A2 2C9 2C19 2D6 3A4 Category B*
Amphetamine 0 0 0 0 0 • Guanfacine extended release
Methylphenidate 0 0 0 0 0 Category C†
Atomoxetine 0 0 0 0* 0 • Amphetamines, methylphenidates, atomoxetine
Bupropion ? ? ? +++ ? Breast milk and breast-feeding
Desipramine 0 0 0 0 0 • Amphetamine and methylphenidates are detectable in breast milk

The table represents the potential for pharmacokinetic drug interactions, potential inhibi-
• Amphetamines have been detected in infant urine
tory effects of ADHD medications on the CYP enzymes and the resultant pharmacokinetic • The AAP considers amphetamines a contraindication for breastfeeding
inhibiton of other substrates. Because patients may be taking multiple medications, it is
useful to anticipate changes in drug metabolism because this may lead to unintended
• It is not known whether quanfacine is excreted into breast milk
side-effects. This table demonstrates that only bupropion has clinically relevant potential
* The maximum recommended human dose of 4 mg/day on a mg/m2 basis resulted in
inhibitory effects on any medication that is metabolized by CYP 2D6. The addition of a
no evidence of harm to the fetus. There are no adequate and well-controlled studies of
drug metabolized by CYP 2D6 to bupropion would likely cause elevated drug blood levels
guanfacine in pregnant women.
that might result in unexpected side-effects. Except for bupropion, there appears to be
no likely inhibitory kinetic drug interaction with ADHD medications and other drugs. This † Animal reproduction studies have shown an adverse effect on the fetus and there are
only accounts for kinetic (metabolism) interactions not pharmacodynamic interactions no adequate and well-controlled studies in humans, but potential benefits may war-
where two drugs interact at related receptor sites (potential of tremor with caffeine and rant use of the drug in pregnant women despite potential risks.
stimulant might have an additive effect when used together).
AAP=American Academy of Pediatrics.
* in vivo Goodman DW. Primary Psychiatry. Vol 17, No 2. 2010.

CYP=cytochrome P450; 0=no inhibition; +++=clinically significant inhibition.


Goodman DW. Primary Psychiatry. Vol 17, No 2. 2010.

TABLE 15
COMPLIMENTARY AND ALTERNATIVE MEDICINE TREATMENTS FOR CHILDHOOD ADHD119,120
CAM treatments are defined as any treatment other than traditional treatments with prescription medication and/or psychotherapies. Complementary treatment means that it is used
in combination with traditional treatments. Alternative treatment means that it is used in lieu of traditional treatment. The use of these treatments as an alternative to traditional
treatments may delay the start of effective measures. The use of CAM treatments for ADHD in children ranges from 12% to 64%.119-122 Interestingly, only 11% of parents revealed
to the physician using CAM with their child.122 Many factors contribute to its continued use despite poor quality research and lack of positive findings. Both physicians and parents
may delay the use of prescription medications because of a prejudice fueled by information highlighting safety considerations. When using CAM treatments, time frames and target
symptoms should be established in order to judge the benefits, as with any treatment in medicine. In order to assess efficacy with high quality data, the following table only includes
well designed, controlled trials or reviews of multiple studies.
Agent Ages (years) N Trial Design Outcome
Homeopathy 123
6–12 43 Randomized, double-blind, randomized, con- No significant differences on Conner’s Global Index-
trolled vs. placebo, 18 weeks Parent, Conner’s Global Index-Teacher, Conner’s
Parent Rating Scale-Brief, Continuous Performance
Test, and the Clinical Global Impression Scale.
Homeopathy125 6–16 62 Initial responders were randomized, placebo Except for a very small significant improvement on
controlled, 14 weeks CGI parent ratings in the Frei study, there was no
benefit of homeopathic treatment in these trials
Homeopathy126 Mean age=10 43 Quasi-randomized, placebo controlled, 30 days,
treatment changes at 10 day intervals
Homeopathy127 7–10 20 Randomized, placebo controlled, compared with
MPH, 60 days
Homeopathy128 Mean age=9 43 Randomized, placebo controlled, 12 weeks
Hypericum perforatum 6–17 54 Randomized, double-blind, randomized, No significant difference on the ADHD-RS IV
(St John’s wort)124 controlled vs. placebo, 8 weeks
Pycnogenol129 Children 61 Randomized, placebo controlled trial, 4 weeks Significant findings on parent and teacher ratings
Pycnogenol 130
Adults 24 Randomized, placebo controlled trial, MPH No difference to placebo on all measures
comparator, 3 week crossover design

Primary Psychiatry 44 February 2010


The Black Book of ADHD

TABLE 15
COMPLIMENTARY AND ALTERNATIVE MEDICINE TREATMENTS FOR CHILDHOOD ADHD (CONT.)119,120
Agent Ages (years) N Trial Design Outcome
Feingold Diet131,132 Children Largest Review of studies Replication studies found no benefit
trial
N=40
Sugar elimination133 Children Review of studies No association found
Megavitamins 134
Children 41 Randomized, controlled, crossover trial, 24 No differences; elevated liver enzymes, significantly
weeks more disruptive classroom behavior with megavita-
mins; elevated liver enzymes
Omega fatty acids135 6–12 54 Randomized, placebo-controlled, augmentation No differences to placebo
study to stimulant treated subjects
Omega fatty acids136 6–13 50 Randomized, placebo-controlled trial; 16 weeks: No differences to placebo
some subjects medicated
Omega fatty acids137 6–12 40 Randomized, placebo-controlled trial; 8 weeks; No differences to placebo
15% subjects medicated
Omega fatty acids138 8–12 29 Randomized, placebo-controlled trial, 12 weeks; Significant differences on 7 of 14 scales used
ADHD with LDs
Omega fatty acids139 7–12 132 Randomized, placebo-controlled trial, 12 weeks; Significant differences on parent ratings, not teach-
crossover extension, 12 weeks er ratings, replicated in the crossover arm
Zinc140 Mean age=9.4 400 Randomized, placebo-controlled trial, 12 Significant differences to placebo
weeks
Zinc141 Mean age=7.9 44 Randomized, placebo-controlled trial; subjects Significant differences to placebo
medicated
Iron142 5–8 23 Randomized, placebo-controlled trial, 12 Significant difference on investigator-rated ADHD
weeks scale and on teacher not parent ratings
EEG biofeedback143 Children and Review of studies No randomized, placebo controlled trials
adolescents
Acupuncture Review of publications on PubMed (accessed No randomized, placebo controlled trials
February 2009)
Chiropactic Review of publications on PubMed (accessed No randomized, placebo controlled trials
treatments February 2009)

CAM=complimentary and alternative medicines; MPH=methylphenidate; EEG=.


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D.W. Goodman

FIGURE 2
PSYCHOTHERAPIES FOR ADOLESCENTS AND ADULTS113
Presentation Treatment Outcome
Symptom
Symptoms Medication
Reduction

History of Organization Improved


Impairments
Failure Techniques Productivity

Dysfunctional
Outcome

Cognitive Cognitive Alter Beliefs


Distortions Therapy by Cognition
Changes

Mood
Disturbance

Increase
Behavioral Behavioral
Engagement
Avoidance Therapy
with Avoided
Activity

Lost
Improve
Opportunity Life Skills
Social
for Skill Building
Interactions
Development
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The Black Book of ADHD

TABLE 27
ADVERSE EVENTS WITH ADHD MEDICATIONS
Side Effect Treatment: Child Treatment: Adult Side Effect Treatment: Child Treatment: Adult
Agitation Reduce total daily dose Reduce total daily dose Headaches Treat with OTC agents Treat with OTC agents
Switch to long-acting agent Switch to long-acting agent May reduce total daily dose May reduce total daily dose until
until acclimates acclimates
Consider underlying mood dis- Consider underlying mood disorder
order May change preparation of May change preparation of agent
agent
Anxiety Distinguish worry/fear from jit- Distinguish worry/fear from jitteri-
teriness/nervousness (below) ness/nervousness (below) Initial Be sure this was not pre- Be sure this was not pre-existing
insomnia existing to medication to medication
Reduce total daily dose Reduce total daily dose
Move timing or eliminate Move timing or eliminate after-
Switch to long-acting agent Switch to long-acting agent afternoon dose noon dose
Consider underlying anxiety Consider underlying anxiety dis- If residual ADHD symptoms If residual ADHD symptoms pres-
disorder order present, may use clonidine HS ent, may use clonidine HS for
Bruxism Decrease total daily dose Decrease total daily dose for sedation sedation
May use alpha agent May need to change compound* May use melatonin 90 May use trazadone HS
minutes before bedtime
May need to change com- May use alpha agonist May use melatonin 90 minutes
pound* before bedtime
Dental night guard to reduce
grinding and morning headache Irritability Occurs shortly after dose or Occurs shortly after dose or as a
as a rebound experience rebound experience
Dietary fiber, mild laxative, Dietary fiber, mild laxative, stool
stool softener softener If occurs 1–2 hours after If occurs 1–2 hours after dosing of
dosing of short-acting agent, short-acting agent, may change to
Decrease May or may not be desired Usually welcomed to help weight may change to long-acting long-acting agent
appetite based on child’s BMI loss agent
If occurs when medication wears
Take morning medication after Problematic if associated with If occurs when medication off, may change to long-acting
meal significant weight and low BMI wears off, may change to agent
long-acting agent
Reduce total daily dose Reduce total daily dose Long-acting agents have different
Long-acting agents have dif- wear off rates, so an alterna-
Change to long-acting agent ferent wear off rates, so an tive long-acting agent may be
Change to long-acting agent alternative long-acting agent preferable
Decrease Not applicable Dose and compound related may be preferable
Co-existing mood disorder needs
libido Co-existing mood disorder to be treated
Reduce total daily dose or change
compound needs to be treated

Dizziness If postural, recommend slower If postural, recommend slower Jitteriness/ Reduce total daily dose Reduce total daily dose
movement from lying to standing movement from lying to standing nervousness
If occurs 1–2 hours after If occurs 1–2 hours after dosing of
If related to vital sign chang- If related to vital sign changes, dosing of short-acting agent, short-acting agent, may change to
es, reduce total daily dose or reduce total daily dose or change may change to long-acting long-acting agent.
change preparation or com- preparation† or compound agent.
Reduce/eliminate daily caffeine
pound Reduce/eliminate daily caf- intake
Treat elevations in pulse and/or
blood pressure feine intake
Distinguish jitteriness/quivering
Dry mouth Sugarless candy/gum Sugarless candy/gum Distinguish jitteriness/quiv- from anxiety/worry
ering from anxiety/worry
Mouthwash that promotes sali- Mouthwash that promotes saliva-
vation necessary for dental/ tion necessary for dental/gingival Sweating Check vital signs May try hydrin or clonidine
gingival protection protection Tics Reduce dose Reduce dose
May use oral pilocarpine Treat tics with guanfacine or Treat tics with guanfacine or
Erectile Not applicable May use PDE5 agents PRN clonidine clonidine
Dysfunction Consider atomoxetine Consider atomoxetine
GI upset/ Treat with OTC agents Treat with OTC agents Weight loss Take medication after morn- Take medication after morning
nausea/ ing meal meal
Usually subsides Usually subsides
stomach-
ache Try MPH patch Try MPH patch Reduce total daily dose Reduce total daily dose
Take with food Take with food Change to long-acting agent or Change to long-acting agent or
non-stimulant non-stimulant
Add high caloric snacks daily Add high caloric snacks daily

* “Change compound” means changing medication compound, not just the preparation of the same compound; † ”Change preparation” means the compound remains the same
BMI=body mass index; PDE5=phosphodiesterase 5 inhibitors; GI=gastrointestinal; OTC=over-the-counter; MPH=methylphenidate.
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D.W. Goodman

AUTHOR’S NOTE hyperactivity and related disorders. Arch Gen Psychiatry. 1996;53:437-446.
32. Claude D, Firestone P. The development of ADHD boys: a 12 year follow up. Can J Behav Sci. 1995;27;226-249.
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