Clinical Review & Education

Review

Treatment of Attention-Deficit/Hyperactivity Disorder

in Adolescents
A Systematic Review
Eugenia Chan, MD, MPH; Jason M. Fogler, PhD; Paul G. Hammerness, MD

Author Audio Interview at

IMPORTANCE Although attention-deficit/hyperactivity disorder (ADHD) is highly prevalent in jama.com
adolescents and often persists into adulthood, most studies about treatment were Related article page 2009
performed in children. Less is known about ADHD treatment in adolescents.
Supplemental content at
jama.com
OBJECTIVE To review the evidence for pharmacological and psychosocial treatment of ADHD
in adolescents.

EVIDENCE REVIEW The databases of CINAHL Plus, MEDLINE, PsycINFO, ERIC, and the
Cochrane Database of Systematic Reviews were searched for articles published between
January 1, 1999, and January 31, 2016, on ADHD treatment in adolescents. Additional
studies were identified by hand-searching reference lists of retrieved articles. Study quality
was rated using McMaster University Effective Public Health Practice Project criteria. The
evidence level for treatment recommendations was based on Oxford Centre for
Evidence-Based Medicine criteria.

FINDINGS Sixteen randomized clinical trials and 1 meta-analysis, involving 2668 participants,
of pharmacological and psychosocial treatments for ADHD in adolescents aged 12 years to 18
years were included. Evidence of efficacy was stronger for the extended-release
methylphenidate and amphetamine class stimulant medications (level 1B based on Oxford
Centre for Evidence-Based Medicine criteria) and atomoxetine than for the extended-release
α2-adrenergic agonists guanfacine or clonidine (no studies). For the primary efficacy measure
of total symptom score on the ADHD Rating Scale (score range, 0 [least symptomatic] to 54
[most symptomatic]), both stimulant and nonstimulant medications led to clinically
significant reductions of 14.93 to 24.60 absolute points. The psychosocial treatments
combining behavioral, cognitive behavioral, and skills training techniques demonstrated
small- to medium-sized improvements (range for mean SD difference in Cohen d, 0.30-0.69)
for parent-rated ADHD symptoms, co-occurring emotional or behavioral symptoms, and
interpersonal functioning. Psychosocial treatments were associated with more robust
(Cohen d range, 0.51-5.15) improvements in academic and organizational skills, such as
homework completion and planner use.

CONCLUSIONS AND RELEVANCE Evidence supports the use of extended-release

Author Affiliations: Division of
methylphenidate and amphetamine formulations, atomoxetine, and extended-release
Developmental Medicine, Boston
guanfacine to improve symptoms of ADHD in adolescents. Psychosocial treatments Children’s Hospital, Boston,
incorporating behavior contingency management, motivational enhancement, and academic, Massachusetts (Chan, Fogler);
organizational, and social skills training techniques were associated with inconsistent effects Department of Psychiatry, Boston
Children’s Hospital, Boston,
on ADHD symptoms and greater benefit for academic and organizational skills. Additional Massachusetts (Fogler,
treatment studies in adolescents, including combined pharmacological and psychosocial Hammerness); Harvard Medical
treatments, are needed. School, Boston, Massachusetts
(Chan, Fogler, Hammerness).
Corresponding Author: Eugenia
Chan, MD, MPH, Division of
Developmental Medicine, Boston
Children’s Hospital, 300 Longwood
Ave, Boston, MA 02115 (eugenia.chan
@childrens.harvard.edu).
Section Editors: Edward Livingston,
MD, Deputy Editor, and Mary McGrae
JAMA. 2016;315(18):1997-2008. doi:10.1001/jama.2016.5453 McDermott, MD, Senior Editor.

(Reprinted) 1997

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 Clinical Review & Education Review
T
he most prevalent neurodevelopmental disorder in child-
hood, attention-deficit/hyperactivity disorder (ADHD), af-
fects approximately 9.5% of children aged 3 years to 17 years
(12% among 12- to 17-year-olds) in the United States.1 Approxi-
mately one-third of childhood ADHD persists into adulthood, with
an estimated adult prevalence of 4.4%.2,3 The Diagnostic and Sta-
tistical Manual of Mental Disorders (Fifth Edition),4 published re-
vised diagnostic criteria for ADHD in 2013, specifically for individu-
als aged 17 years or older, to reflect more recent research supporting
the chronicity, presentation, and range of ADHD-related impair-
ments that occur during adolescence and adulthood (Table 1 and
eTable 1 in the Supplement).
Compared with those without ADHD, adolescents with this dis-
order are at increased risk for many adverse outcomes in adult-
hood, including impaired physical health, mental health (eg, anxi-
ety, substance abuse, depression, suicide), and psychosocial
functioning (eg, academic underachievement, relationship difficul-
ties, underemployment, legal troubles).2,8 Estimated societal costs
attributable to ADHD range from $143 billion to $266 billion, pri-
marily due to health care costs related to treatment (primarily pre-
scriptions and outpatient visits) and educational (eg, special edu-
cation services, disciplinary) costs for children and adolescents, and
lost productivity for adults.9,10
Appropriate treatment may mitigate the risk of these adverse
outcomes; however, adolescents with ADHD are less likely to seek
or continue treatment. Despite concerns about stimulant overpre-
scription in children,11 recent estimates indicate that only 45.3% of
12- to 17-year-olds with ADHD reported receiving medication dur-
ing the past week, whereas 12.5% had received behavioral therapy
during the past year, and 14.3% reported receiving neither ADHD
medication nor behavioral therapy.12 Among adolescents transition-
ing into young adulthood, the rate of prescription receipt for ADHD
medication decreased faster than the rate of reported symptoms,
suggesting premature treatment cessation despite continued
symptoms.13
Clinicians rely on clinical practice guidelines for pediatric ADHD
treatment.14,15 However, such guidelines are derived from key stud-
ies in school-aged and preschool children, and from other studies
aggregating children and adolescents.16,17 Even if some adolescent-
specific issues, such as substance use risk and treatment adher-
ence, are addressed separately,14,15 the guideline recommenda-
tions generally represent an extrapolation of the evidence base from
younger children to adolescents, which may not be appropriate.18
Thus, our objective was to review the available evidence specifi-
cally on adolescents for the pharmacological and psychosocial treat-
ment of ADHD.
Methods
Search Strategy
We searched CINAHL Plus, MEDLINE, PsycINFO, ERIC, and the
Cochrane Database of Systematic Reviews for English-language
articles published in peer-reviewed journals between January 1,
1999, and January 31, 2016, using the search terms ADHD,
attention-deficit, adolescent, and adolescence, and the filters clini-
cal trial, randomized clinical trial, or systematic review to identify
potential articles addressing pharmacological or psychosocial
1998 JAMA May 10, 2016 Volume 315, Number 18 (Reprinted)
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Treatment of Attention-Deficit/Hyperactivity Disorder in Adolescents
Take-Home Messages
Pharmacological Treatment
• Stimulant class medications (extended-release methylphenidate
and amphetamine formulations) are recommended as first-line
agents for the treatment of attention-deficit/hyperactivity
disorder (ADHD) in adolescents, followed by atomoxetine
and extended-release guanfacine.
• Although dexmethylphenidate and extended-release clonidine
are approved by the US Food and Drug Administration with
demonstrated efficacy for the entire pediatric age range, studies
specifically in adolescents are lacking.
Psychosocial Treatment
• Psychosocial treatments are associated with greatest effect on
the functional outcomes, such as homework completion,
organizational skills, and parent-reported symptoms of ADHD,
and co-occurring psychopathology (in that order).
• Treatment packages consist of a variety of behavioral, cognitive
behavioral, and skills training techniques that are directed at the
adolescent, parent, teacher, or both the parent and teacher and
are generally delivered in real-world home or school settings.
Recommendations for Future Research
• Investigating mediators and moderators of treatment among
adolescents with ADHD is needed to better understand
differential treatment effects.
• The efficacy of combined pharmacological and psychosocial
treatment compared with either treatment alone needs to be
studied in adolescents with ADHD.
• Further treatment studies need to be conducted in adolescents
with ADHD and comorbid psychiatric and substance use disorders.
interventions for youth with ADHD. We hand-searched the refer-
ence lists of retrieved articles and relevant systematic reviews to
identify additional studies.
We reviewed titles, abstracts, and full text if necessary to
determine relevance. Psychopharmacological and psychosocial
studies were included if (1) participants met Diagnostic and Statis-
tical Manual of Mental Disorders (Fourth Edition) or Diagnostic and
Statistical Manual of Mental Disorders (Fourth Edition, Text Revi-
sion) diagnostic criteria for ADHD, (2) participants were random-
ized to treatment groups, (3) treatment efficacy was evaluated
using at least 1 valid outcome measure for core ADHD symptoms
or related functioning, and (4) results were reported separately for
the age group of 12 years to 18 years or grade equivalent (middle
or high school).
In addition, pharmacological studies using a double-blind de-
sign must have evaluated extended-release medications approved
by the US Food and Drug Administration (FDA) for the treatment of
pediatric ADHD. Meta-analyses were included if the pooled data were
from studies meeting the 4 criteria listed above.
We excluded studies that (1) selected participants with both
ADHD and diagnosed comorbid psychiatric or developmental con-
ditions (eg, conduct disorder, depression, anxiety, autism, intellec-
tual disabilities), (2) included participants with ADHD secondary to
a medical condition (eg, traumatic brain injury), (3) focused on labo-
ratory, imaging, or neuropsychological assessment outcomes or out-
comes pertinent only to comorbid conditions, or (4) tested effi-
cacy of nonstandard interventions.
jama.com
 Treatment of Attention-Deficit/Hyperactivity Disorder in Adolescents
Table 1. Classic Presenting Features of Attention-Deficit/Hyperactivity Disorder in School-Aged vs Adolescent Populations5-7
Symptom School-Aged Children
• Difficulty sustaining attention (except to video games)
• Does not listen
• Difficulty following multistep directions
Inattention
• Loses things, such as school materials,
has a messy locker, book bag, or desk
• Easily distracted or forgetful
• Squirms and fidgets
• Runs or climbs excessively
• Cannot play or work quietly
• Talks excessively
Hyperactive-impulsive
• On the go, driven by “a motor”
• Blurts out answers
• Cannot wait his/her turn
• Intrudes on or interrupts others
• Difficulty sitting still
• Easily overwhelmed
Dysfunction at school
• Easily bored
• Speaks out in class
Outcome Reporting
The primary efficacy measure for pharmacological studies for this
review was the mean change in absolute ADHD Rating Scale total
symptom scores (range, 0-54 with 54 indicating the greatest level
of symptom severity)19 from baseline to study end point for the treat-
ment group vs the placebo group, or the mean difference in symp-
tom score change between the treatment and placebo groups. A
clinically meaningful response is generally considered to be improve-
ment of 25% or greater from baseline (a within-group reduction of
approximately 10-15 absolute points20 or a mean difference of ap-
proximately 6-7 points between the treatment and placebo
groups).21
Psychosocial studies reported outcomes as effect sizes, most
commonly using the Cohen d, where d = 1.0 represents a 1-SD dif-
ference in outcome measure scores from baseline to end point within
treatment groups, or a mean of 1-SD difference in score change from
baseline between treatment groups. By convention, a Cohen d equal
to 0.2 is considered to represent a small effect, a Cohen d equal to
0.5 represents a medium effect, and a Cohen d equal to 0.8 repre-
sents a large effect.22
Evidence Grading
Two authors independently rated the quality of individual pharma-
cological (E.C. and P.G.H.) and psychosocial (E.C. and J.M.F.) treat-
ment studies using the McMaster University Effective Public Health
Practice Project quality assessment tool for quantitative studies,23
resolving discrepancies through consensus (eBox in the Supple-
ment). Oxford Centre for Evidence-Based Medicine criteria were used
to assess the strength of the evidence criteria for the treatment
recommendations.24
Results
Search Retrieval Results
The initial search yielded 9164 articles; of these, 1386 were
clinical trials. After applying the inclusion and exclusion criteria
and hand-searching reference lists from systematic reviews and
relevant articles for additional records, we identified 6 double-
blind randomized clinical trials (RCTs) and 1 meta-analysis of
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Review Clinical Review & Education
Adolescents and Adults
• Difficulty sustaining attention to reading or paperwork
• Poor level of concentration
• Difficulty finishing tasks
• Misplaces things, such as wallets, keys, or mobile telephones,
has poor time management, works twice as hard for half as much
• Easily distracted or forgetful; may seem scattered at home or work
• Inner restlessness
• Fidgets when seated (eg, drums fingers, taps foot, flips pens)
• Easily overwhelmed
• Talks excessively
• Self-selects active jobs or activities
• Makes impulsive decisions
• Drives too fast, takes impulsive risks
• Often irritable or quick to anger
• Teachers complain about inattention, lack of motivation,
or being overly social
• Procrastination
• Missing assignments, poor test grades
• Grades fall and avoids or cuts class or school
pharmacological treatments 25-31 and 10 RCTs of psychosocial
treatments32-41 for the treatment of ADHD in adolescents, involv-
ing 2668 total participants (eFigure in the Supplement).
Pharmacological Treatment
The extended-release medications approved by the FDA for the
treatment of ADHD include stimulants (eg, methylphenidates and
amphetamines) and nonstimulants (eg, atomoxetine and
extended-release α2-adrenergic agonists) (Table 2). Table 3 and
eTable 2 in the Supplement provide details regarding the design,
participants, and results (ie, core symptom improvement or lack of
improvement) from the 6 double-blind RCTs and 1 meta-analysis of
FDA-approved ADHD medications to treat core symptoms in ado-
lescents (1752 patients total).
Evidence for Treatment With Methylphenidate
Two multicenter studies investigated the effects of extended-
release methylphenidate in its osmotic-release oral system26 and
transdermal system28 formulations. Both methylphenidate for-
mulations were superior to placebo. Specifically, the methylphe-
nidate osmotic-release oral system treatment group experienced
a mean reduction of 47% (mean [SD], −14.93 points [10.72
points]) in investigator-rated ADHD Rating Scale symptom scores
compared with a mean reduction of 31% (mean [SD], −9.58
points [9.73 points]) in the placebo group (P = .001).26 Similarly,
adolescents receiving the methylphenidate transdermal system
(vs a placebo transdermal system) experienced a greater reduc-
tion in ADHD symptom scores (mean, −9.96 points; 95% CI,
−13.39 points to −6.53 points).28
We identified no RCTs of dexmethylphenidate in adolescents,
although 1 meta-analysis found dexmethylphenidate was associ-
ated with studies in the 6- to 17-year age group.42
Evidence for Treatment With Amphetamines
Two multicenter studies investigated the efficacy of amphet-
amines (extended-release mixed amphetamine salts and lisdexam-
fetamine), using placebo-controlled, parallel-group forced-dose
titration designs25,29; both formulations were superior to placebo.
Adolescents who received extended-release mixed amphetamine
salts demonstrated significant improvements in ADHD total
(Reprinted) JAMA May 10, 2016 Volume 315, Number 18 1999
 Clinical Review & Education Review Treatment of Attention-Deficit/Hyperactivity Disorder in Adolescents

Table 2. Mechanism of Action, Dosing, and Adverse Effects of Extended-Release Medications Approved by the US Food and Drug Administration
(FDA) to Treat Attention-Deficit/Hyperactivity Disorder in Adolescents
Category and Extended-Release
Medication Class Mechanism of Action Medication Brand Name Dosing and Other Instructions Adverse Effects
Stimulants
Methylphenidate • Capsule: 18 mg, 27 mg, 36 mg, or 54 mg
osmotic-release oral Concertaa • Do not crush, chew, or open
system
Headache, decreased appetite,
Inhibits reuptake Methyphenidate • Patch: 10 mg, 15 mg, 20 mg, or 30 mg
Daytrana insomnia, stomachache, nausea,
of norepinephrine transdermal system • Remove patch after 9 h
Methylphenidate irritability, dizziness, decreased
and dopamine into • Capsule: 5 mg, 10 mg, 15 mg, 20 mg, weight, and mild increase in
presynaptic neurons 25 mg, 30 mg, or 40 mg pulse and blood pressure level
Dexmethylphenidate Focalin XRa • Capsule may be opened
• Equivalent to half the daily dose of other
methylphenidate formulations
Promotes release
of dopamine and • Capsule: 5 mg, 10 mg, 15 mg, 20 mg,
Mixed amphetamine
norepinephrine from Adderall XRa 25 mg, or 30 mg Headache, decreased appetite,
salts
presynaptic neurons • Capsule may be opened insomnia, stomachache, nausea,
Amphetamine and inhibits reuptake irritability, dizziness, decreased
Converted to active weight, and mild increase in
• Capsule: 20 mg, 30 mg, 40 mg, 50 mg, pulse and blood pressure level
dextroamphetamine
Lisdexamfetamine Vyvanse 60 mg, or 70 mg
in bloodstream
• Capsule may be opened
(prodrug)
Nonstimulants
Selectively inhibits • Headache, somnolence,
presynaptic abdominal pain, nausea,
• Capsule: 10 mg, 18 mg, 25 mg, 40 mg,
norepinephrine decreased appetite, vomiting,
60 mg, 80 mg, or 100 mg
SNRI transporter, with Atomoxetine Strattera dizziness, and rare hepatic
• Do not crush or chew
secondary effects on failure
• Approved for monotherapy
dopaminergic systems • FDA black box warning
for suicidal ideation
Selectively stimulates • Tablet: 1 mg, 2 mg, 3 mg, or 4 mg
α2A-adrenergic • Do not crush or chew
Guanfacine Intuniva
receptors in the • Approved for monotherapy and as adjunct Somnolence, headache, fatigue,
α2-Adrenergic prefrontal cortex to stimulants dizziness, sedation, insomnia,
agonist Stimulates central • Tablet: 0.1 mg dry mouth, and decreased pulse
α2-adrenergic • Do not crush or chew and blood pressure level
Clonidine Kapvaya
receptors to reduce • Approved for monotherapy and as adjunct
sympathetic outflow to stimulants

Abbreviation: SNRI, selective norepinephrine reuptake inhibitor.

a
Generic version is available.

symptom scores (−17.8 points vs −9.4 points in the placebo group,
P < .001), with greater effect on hyperactive-impulsive symptoms
than on inattentive symptoms.25
Lisdexamfetamine dimesylate is a long-acting prodrug stimu-
lant, yielding active dextroamphetamine after cleavage of lysine in
the bloodstream.43 A recent meta-analysis of pediatric (age group,
6 years to 17 years) RCTs demonstrated a favorable association of
lisdexamfetamine treatment with ADHD symptoms compared with
placebo44; however, we found only 1 RCT specifically conducted in
adolescents.29 In this forced-dose titration study,29 all lisdexamfe-
tamine dose groups experienced greater reductions (range, −18.3
points to −21.1 points) in ADHD total symptom scores compared with
placebo (−12.8 points) (P < .006).
Evidence for Treatment With Atomoxetine
Atomoxetine is a selective norepinephrine reuptake inhibitor ap-
proved by the FDA for ADHD monotherapy. A meta-analysis pool-
ing data from 6 double-blind, placebo-controlled RCTs in partici-
pants aged 6 years to 17 years analyzed the results separately for the
12- to 17-year-old subgroup (n = 176).31 Atomoxetine was associ-
ated with clinically significant improvements in ADHD total symp-
tom scores (mean [SD], −13.99 points [12.97 points] vs −6.95 points
[10.07 points] in the placebo group) (P < .001).
We found only 1 multisite, double-blind (not placebo-
controlled) RCT in adolescents, which compared a slow atomox-
etine titration schedule (0.5 mg/kg/d for 7 days to 9 days,
1.0 mg/kg/d for 7 days to 9 days, and then 1.2 mg/kg/d) vs
a fast titration schedule (0.5 mg/kg/d for ⱖ3 days and then
1.2 mg/kg/d) during an 8-week acute treatment phase followed
by a low-dose maintenance phase (0.8 mg/kg/d) vs a high-dose
phase (1.4 mg/kg/d) during an additional 40 weeks.30 Partici-
pants were randomized at entry to each phase of the trial. Com-
pared with baseline, the slow and fast titration groups experi-
enced reductions in ADHD total symptom scores (mean [SD],
−16.48 points [0.81 points] and −17.26 points [0.79 points],
respectively) during the acute phase (within-group P < .001). Dur-
ing the maintenance phase, the low-dose group experienced a
significant increase in symptom scores (mean [SD], 3.80 points
[1.05 points], P < .001), but the high-dose group did not (mean
[SD], 1.93 points [1.05 points], P < .07).
Evidence for Treatment With α2-Adrenergic Agonists
The selective extended-release α2-adrenergic agonists guanfacine
and clonidine offer a treatment alternative for patients in whom
stimulants are contraindicated, poorly tolerated, or only partially
effective. Both are approved by the FDA for monotherapy and as

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 Table 3. Double-Blind, Randomized Clinical Trials (RCTs) Evaluating the Efficacy of FDA-Approved Extended-Release ADHD Medications in Adolescents
Sample Quality

jama.com
Source Size Intervention Duration of Treatment Primary Efficacy Measurea Findings Ratingb
Stimulants
• Methylphenidate osmotic-release • Investigator-rated mean (SD) change, −14.93 points (10.72 points) vs
oral system of 18 mg, 36 mg, Mean change from baseline to −9.58 points (9.73 points) for placebo, P = .001c
Wilens et al,26 Open-label titration for 4 wk, followed by
177 54 mg, or 72 mg end point in investigator-rated • Approximately one-third of adolescents required 72 mg 1B
2006 2-wk double-blind phase
• Individualized dosing based ADHD Rating Scale score of methylphenidate to achieve response
on open-label titration phase
• Methylphenidate transdermal • Clinician-rated mean difference, −9.96 points (95% CI, −13.39 points
Mean difference between
system of 10 mg, 15 mg, 20 mg, Double-blind dose optimization phase to −6.53 points), P < .001 vs placeboc
Findling et al,28 groups in change from baseline
217 or 30 mg for 5 wk, followed by 2-wk double-blind • 65.5% of methylphenidate group vs 30.6% of the placebo group rated 2B
2010 to end point in clinician-rated
• Individualized dosing based maintenance phase by clinicians as much or very much improved
ADHD Rating Scale IV score
on dose optimization phase
• Extended-release mixed • Improved investigator-rated ADHD symptom scores in adolescents
amphetamine salts forced-dose Mean change from baseline to at all dosages (mean change from baseline, −17.8 points vs −9.4
Spencer et al,25 Double-blind, forced-dose titration
287 titration of 10 mg, 20 mg, 30 mg, end point in investigator-rated points for placebo, P < .001) 1B
2006 for 4 wk
and 40 mg ADHD Rating Scale IV score • 51.9% to 70.7% of intervention group vs 26.9% of placebo group rated
• 1:1:1:1 ratio as much or very much improved (P < .01)
• Improved clinician-rated ADHD symptom scores in adolescents
• Lisdexamfetamine forced-dose
Mean change from baseline to at all dosages (mean change from baseline, −18.3 points to −21.1
Findling et al,29 titration of 30 mg, 50 mg,
314 4 wk end point in clinician-rated points vs −12.8 points for placebo, P < .006) 1B
2011 and 70 mg
Treatment of Attention-Deficit/Hyperactivity Disorder in Adolescents

ADHD Rating Scale IV score • 69.1% of intervention group vs 39.5% of placebo group rated as much
• 1:1:1 ratio
or very much improved (P < .001)
Nonstimulants
Meta-analysis of 6 double-blind, • Improved investigator-rated ADHD symptom scores in adolescents
Mean change from baseline to
Wilens et al,31 placebo-controlled RCTs of (mean [SD] change from baseline, −13.99 [12.97] vs 6.95 [10.07]
176 6 to 8 wk end point in investigator-rated 1A
2006 atomoxetine with subgroup analysis for for placebo, P < .001)
ADHD Rating Scale score

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12- to 17-year-olds
• Slow titration of atomoxetine
(0.5 mg/kg/d for 7 d to 9 d,
1.0 mg/kg/d for 7 d to 9 d,
267d and then 1.2 mg/kg/d) vs fast
titration (0.5 mg/kg/d for 3 d,
30 and then 1.2 mg/kg/d)
Wietecha et al,
• No placebo
2009
• Low dose of atomoxetine
(0.8 mg/kg/d) vs high dose
178e
8 wk
Mean change from baseline to
end point (for both phasesd,e)
in clinician-rated ADHD Rating
Scale score
40 wk
• Mean final dose: 1.32 mg/kg/d
• Improved clinician-rated ADHD symptoms from baseline
• Mean (SD) change, −17.26 points (0.79 points) for slow titration
group (P < .001 vs fast titration group)
• Mean (SD) change, −16.48 points (0.81 points) for fast titration group
(P < .001 vs slow titration group)
• No difference between groups
2B
• Increased clinician-rated ADHD symptom scores from baseline within
low-dose group (mean [SD], 3.80 points [1.05 points], P < .001)
but not within high-dose group (mean [SD], 1.93 points [1.05 points],

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(1.4 mg/kg/d)
P < .07)
• No placebo
• No difference between dose groups
• Improved investigator-rated ADHD symptoms from baseline
(mean change, −24.6 points vs −18.5 points for placebo, P < .001)
• Extended-release guanfacine Dose optimization phase for 7 wk, Mean change from baseline to • Greater proportion of intervention participants rated as normal
Wilens et al,27
314 • Optimized dose: 0.05 mg/kg/d followed by 6-wk dose end point in investigator-rated or borderline mentally ill (50.6% for guanfacine vs 36.1% for placebo, 1B
2015
to 0.12 mg/kg/d maintenance phase ADHD Rating Scale IV score P = .01)
• Mean optimal guanfacine dose of 4.3 mg (range, 1 mg to 7 mg)
• Weight-adjusted optimal dose of 0.05 mg/kg to 0.12 mg/kg
c
Abbreviations: ADHD, attention-deficit/hyperactivity disorder; FDA, Food and Drug Administration. Improved investigator or clinician-, parent-, and self-rated ADHD symptom scores in intervention group.
a d
The ADHD Rating Scale consists of 18 items corresponding to Diagnostic and Statistical Manual of Mental During the acute treatment phase.
Disorders (Fourth Edition) criteria. Each are scored on a 4-point Likert scale from 0 (no symptoms) to 3 (severe e
During the maintenance phase.
symptoms). Total scores range from 0 (least symptomatic) to 54 (most symptomatic).19
b
Based on Oxford Centre for Evidence-Based Medicine criteria.

(Reprinted) JAMA May 10, 2016 Volume 315, Number 18

Review Clinical Review & Education

2001
 Clinical Review & Education Review
adjuncts to stimulants. Although 2 recent systematic reviews of
placebo-controlled pediatric RCTs concluded that both extended-
release guanfacine and clonidine were associated with efficacy
for core ADHD symptoms,45,46 we identified only 1 level 1B (based
on Oxford Centre for Evidence-Based Medicine criteria) RCT of
extended-release guanfacine monotherapy in adolescents.27 In
this 13-week, double-blind, placebo-controlled study,27 adoles-
cents who received extended-release guanfacine experienced a
mean reduction in ADHD symptom scores of 24.6 points com-
pared with 18.5 points in those who received placebo (P < .001).
Even though other published RCTs of extended-release guan-
facine monotherapy reported results separately for 13- to
17-year-olds,47,48 these studies were insufficiently powered a priori
to detect differences by age subgroups. Similarly, we did not iden-
tify any published, double-blind, placebo-controlled RCTs of ex-
tended-release clonidine monotherapy or adjunctive extended-
release guanfacine or clonidine sufficiently powered for adolescent
subgroup analysis.46,49
Tolerability of Stimulant and Nonstimulant Medications
The studies already mentioned reported the adverse effect pro-
files of the methylphenidate osmotic-release and transdermal
systems, extended-release mixed amphetamine salts, lisdexamfe-
tamine, atomoxetine, and extended-release guanfacine, which
were consistent with the findings of previously published studies
of the same medication class in other age groups.25-31 Common
treatment-emergent adverse effects associated with all stimu-
lants included reduced appetite, headache, irritability, abdominal
pain, nausea, insomnia, and weight loss. For the methylphenidate
transdermal system, localized skin irritation also was reported.
Associations with cardiovascular effects included small mean in-
creases in systolic and diastolic blood pressure and heart rate. Com-
mon treatment-related adverse effects associated with atomox-
etine and extended-release guanfacine included nausea, decreased
appetite, dizziness, abdominal pain, fatigue, headache, vomiting, and
somnolence. Atomoxetine was not associated with changes in vital
signs, whereas extended-release guanfacine was associated with mi-
nor reductions in pulse and blood pressure.
Psychosocial Treatments
The psychosocial treatments for ADHD include (1) behavior
therapy, which emphasizes selective reinforcement of desired
behavior and selective ignoring of problem behavior (ie, behavior
contingency management); (2) direct skills training to address
common ADHD-related deficits, such as organizational (eg, use of
a planner), time management, and study skills; and (3) cognitive
behavioral therapy (CBT) to identify negative or automatic
thoughts and modify them through techniques, such as cognitive
restructuring, motivational interviewing, and mindfulness.
We identified 10 RCTs (involving 916 participants) of psycho-
social treatments for adolescents with ADHD (Table 4); all were
multicomponent treatments combining behavioral, cognitive
behavioral, and training interventions to target ADHD-related
functional outcomes (additional details appear in eTable 3 in the
Supplement).32-41 Although 2 studies were level 1B RCTs (based
on Oxford Centre for Evidence-Based Medicine criteria), most
were considered level 2B studies24 due to inadequately described
randomization procedures, blinding, and analysis of dropouts, as
2002 JAMA May 10, 2016 Volume 315, Number 18 (Reprinted)
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Treatment of Attention-Deficit/Hyperactivity Disorder in Adolescents
well as small sample sizes. Most studies did not exclude partici-
pants who were taking ADHD medication or had symptoms of
comorbid psychiatric conditions.
Efficacy for ADHD Symptoms
Eight studies32,34-40 found inconsistent associations of psychoso-
cial treatments with ADHD symptoms. Most included adolescent
organizational skills training coupled with parent and teacher train-
ing in behavioral contingency management,34-39 whereas 2 used
CBT.32,40 In 5 studies,34,35,37-39 psychosocial treatments were asso-
ciated with parent-rated inattention compared with the control
group (Cohen d range, 0.3 to 1.42). Two studies reported associa-
tions with greater improvement in parent-rated hyperactive-
impulsive symptoms (Cohen d = −1.03 for treatment groups vs
Cohen d =−0.16 for control groups36 and between-group Cohen
d = 1.20).39 Group CBT was associated with greater reductions in
parent-rated ADHD symptoms from baseline compared with the
control group (mean difference, −9.11 points [95% CI, −11.48 points
to −6.75 points]; Cohen d = 8.4; P < .001).40 There were not any
studies associated with significant effects on teacher-rated ADHD
symptoms.
Efficacy for Co-occurring Emotional and Behavioral
Symptoms
Five studies32,33,38-40 found inconsistent associations of psychoso-
cial therapies with co-occurring emotional and behavioral symp-
toms. The Challenging Horizons Program (CHP) afterschool
study, which incorporated skills training, coaching, and behavior con-
tingency management in the school setting, led to improvements
in parent-rated internalizing symptoms (Cohen d = 0.55 vs
Cohen d = 0.10 for the control group; P < .05).33 Neither the CHP
afterschool study nor the more-limited CHP mentor model study,
which trained teachers to deliver elements of the intervention to stu-
dents, significantly improved parent- or teacher-rated oppositional-
defiant symptoms compared with community care.38
Adolescents in the Supporting Teens’ Academic Needs Daily
(STAND) intervention group,39 which provided academic skills train-
ing to both the parents and the adolescent, achieved greater im-
provement compared with the control group for parent-rated (but
not teacher-rated) oppositional-defiant symptoms (between-
group Cohen d = 0.83; P < .05). Both CBT with skills training and CBT
alone led to large within-group (but not between-group) reduc-
tions in anxiety, depressive, and oppositional-defiant symptoms32;
however, adolescents who received group CBT did not experience
such improvements relative to the control group (patients in the con-
trol group were randomized to a waiting list to receive the interven-
tion at a later time).40
Efficacy for Academic and Organizational Outcomes
Nine studies32-39,41 included training in academic and organiza-
tional skills (eg, study skills, materials organization, homework
monitoring and completion) in their intervention packages. Most
were associated with minimal effects on grades.33,35,36,39 How-
ever, participants in the small Homework, Organization, and Plan-
ning Skills (HOPS) study achieved mean grade point averages
(GPAs) in the high C range (GPA range, 2.84-2.99) compared with
the control group with GPAs in the low C range (GPA range, 2.12-
2.14) (Cohen d range, 0.69-0.89; P < .02).34 In the largest RCT,
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 Table 4. Summary of Randomized Clinical Trials Evaluating Efficacy of Psychosocial Treatment for Adolescents With Attention-Deficit/Hyperactivity Disorder (ADHD)

Types of Effectsa

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Sample Additional Experimental vs ADHD Co-occurring Emotional and Functioning and Academic and Quality
Source Size Information Control Interventions Symptoms Behavioral Symptoms Impairment Organizational Outcomes Ratingb
c
Challenging Horizons Program Studies
Improved parent-rated
Taking
internalizing but not
Molina ADHD Afterschool model vs support
externalizing symptoms for No effects on parent-rated No effects on percentage of adolescents with
et al,33 23 medications as usual over 10 wk during fall Not measured 2B
afterschool model vs control impairment passing grades or on grade point average
2008 (25% to semester in middle schools
group (Cohen d = 0.55 vs
36%)
d = 0.10, P < .05)
Improved parent-rated
Have Consultative mentor model Improved parent-rated inattention
social functioning on some
Evans comorbid (teachers taught to deliver but not hyperactive symptoms No effects on percentage of adolescents with
but not all measures in
et al,35 79 conditions intervention to students) vs in mentor model vs control group Not measured failing grades or on parent- or teacher-rated 2B
mentor model vs control
2007 (55% to community care over 3 y (Cohen d = 0.76 for between-group academic functioning
group (Cohen d = 0.40 for
70% ) in middle schools difference)
between-group difference)
• Improved parent-rated • Reduced teacher-rated but not parent-rated
hyperactive-impulsive symptoms academic impairment in afterschool model
Taking Afterschool model plus family
but not inattention in afterschool plus family check-up vs control group
Evans ADHD check-up (adds parent-directed No effects on parent- or
model plus family check-up vs (Cohen d = −0.45 vs d = 0.10, P < .04)
et al,36 49 medications motivational interviewing) vs Not measured teacher-rated social 2B
control group (Cohen d = −1.03 vs • Improved academic performance in language
2011 (52% to community care over 1 y impairment
Treatment of Attention-Deficit/Hyperactivity Disorder in Adolescents

d = −0.16, P < .01) arts and social studies in afterschool model

61%) in middle schools
• No significant effect on teacher plus family check-up vs control group
ratings
Taking Improved parent-rated inattention Reduced parent-rated
Evans Coaching vs community care
ADHD but not hyperactive symptoms family impairment for No effects on teacher-rated academic
et al,37 36 over 1 school year Not measured 2B
medications in coaching vs control group coaching vs control group performance
2014 in high schools
(50%) (between-group P = .04) (between-group P = .04)

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• Improved parent-rated inattention • Improved homework performance
but not hyperactive symptoms for afterschool model vs community care
for afterschool model vs at year-end (Cohen d range = 0.42 to 0.44,
community care (Cohen d = 0.51, P < .01) and at 6-mo follow-up
P < .002) at year-end and at 6-mo (d range = 0.38 to 0.61, P < .03)
• No effects on parent- or
Taking follow-up (d = 0.63, P < .001) • Afterschool model vs mentor model only
Afterschool model vs mentor No effects on parent- or teacher-rated impairment
Evans ADHD • Improved parent-rated inattention at 6-mo follow-up (Cohen d = 0.49, P < .01)
model vs community care over teacher-rated • All groups improved on
et al,38 326 medications but not hyperactive symptoms • Improved task planning for afterschool model 1B
1 school year, with additional oppositional-defiant parent-rated social skills
2016 (44% to for afterschool model vs mentor vscommunity care (Cohen d = 0.51, P < .007)
6-mo follow-up symptoms • No differences between
52%) model only at 6-mo follow-up at year-end and at 6-mo follow-up (d = 0.57,
groups
(Cohen d = 0.55, P < .003) P < .001)

Copyright 2016 American Medical Association. All rights reserved.

• No significant differences between • For afterschool model vs mentor model only
mentor model vs community care at 6-mo follow-up (Cohen d = 0.59, P < .001)
at year-end or at 6-mo follow-up • No effects for mentor model vs
community care
Other Multicomponent Treatment Studies
Supporting Teens’ Academic • No effects on • Improved parent-rated but not teacher-rated
Taking
Needs Daily (STAND; parent-rated academic problems for STAND group vs
ADHD Improved parent-rated but not Improved parent-rated
motivational enhancement parent-child conflict treatment as usual (Cohen d = 1.30, P < .05)
medications teacher-rated inattention and but not teacher-rated
Sibley for parents, parent training to • Improved • Improved discrete organizational skills
(39%) and hyperactive-impulsive symptoms for oppositional-defiant
et al,39 36 improve adolescents’ academic, adolescent-rated (eg, use of planner) for STAND group vs 2B
up to 78% STAND group vs treatment as usual symptoms for STAND group
2013 organizational, and behavioral parent-child conflict treatment as usual (Cohen d = 5.15, P < .05)
have (Cohen d range = 1.20 to 1.42, vs treatment as usual
skills, and behavioral for STAND group vs • Improved grade point average for STAND group
comorbid P < .05) (Cohen d = 0.83, P < .05)
contracting) vs treatment treatment as usual vs treatment as usual (Cohen d = 0.25, P < .05)
conditions
as usual over 5 mo (Cohen d = 0.65, P < .05)

(continued)

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Review Clinical Review & Education

2003
 2004
Table 4. Summary of Randomized Clinical Trials Evaluating Efficacy of Psychosocial Treatment for Adolescents With Attention-Deficit/Hyperactivity Disorder (ADHD) (continued)

Types of Effectsa
Sample Additional Experimental vs ADHD Co-occurring Emotional and Functioning and Academic and Quality
Source Size Information Control Interventions Symptoms Behavioral Symptoms Impairment Organizational Outcomes Ratingb
Taking • Improved parent-rated but not teacher-rated
ADHD Homework, Organization, task planning (Cohen d = 1.05, P = .006) and
medications Planning Skills (HOPS; organized actions (d = 0.88, P < .00) for HOPS
Improved parent-rated inattention Improved parent-rated life
Langberg (62% to organizational skills training, vs control group
but not hyperactive-impulsive impairment in HOPS vs
et al,34 47 70%) and and parent and teacher Not measured • Improved parent-rated homework completion 2B
symptoms in HOPS vs control group control group
2012 30% to 50% contingency management (Cohen d = 0.85, P = .001)
(Cohen d = 0.52, P = .02) (Cohen d = 0.69, P < .00)
have at home and at school) vs • Higher overall grade point average (high C
Clinical Review & Education Review

comorbid control groupd over 11 wk range in treatment vs low C range

conditions in control group)
Homework monitoring and
Survey, Question, Read, Write,
Improved percentage of homework turned in for
Meyer and Recite (SQR4) self-monitoring
None adolescents in the SQ4R and parent monitoring
Kelley,41 42 vs parent monitoring (study Not measured Not measured Not measured 2B
reported intervention groups (range, 90% to 92%) vs
2007 skills training, behavioral
control group (60%), P < .001
contingency management) vs
control groupd over 9 wk

JAMA May 10, 2016 Volume 315, Number 18 (Reprinted)

Cognitive Behavioral Therapy (CBT) Studiese
• Improved
investigator-rated global
functioning for CBT vs
Improved adolescent- and
control group (mean
Have parent-rated ADHD symptoms from
difference, −7.58 points,
Vidal comorbid baseline for CBT vs control group
Manualized group CBT vs No effects on anxiety or Cohen d = 2.3, P < .001)
et al,40 119 conditions (adolescent mean difference, −7.46 Not measured 1B
control groupd over 12 wk depressive symptoms • Improved parent-rated
2015 (12% to points, Cohen d = 7.5; parent mean
but not adolescent-rated
13%) difference, −9.11 points, d = −8.4,
functioning for CBT vs
P < .001)

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control group (mean
difference, 4.02,
Cohen d = 3.75, P < .05)
• Reduced parent-reported
but not
adolescent-reported
• Improved depression,
Taking parent-teen conflict
anxiety, oppositional- • Reduced homework problems in both groups
ADHD compared with baseline
Plan my life (PML; CBT with defiant, and conduct (ηρ2 = 0.11, P < .001)
medications for both groups
skills teaching and motivational • Improved parent-rated ADHD disorder symptoms • Greater improvement in planning skills for PML
(78%) and (ηρ2 = 0.06, P < .001)
Boyer interviewing) vs symptoms compared with baseline compared with baseline vs SFT (ηρ2 = 0.23, P < .05)
approxi- • No between-group
et al,32 159 solution-focused treatment for both the PML and SFT groups for both the PML • Improved performance on 2 2B

Copyright 2016 American Medical Association. All rights reserved.

mately differences
2015 (SFT; CBT with motivational (ηρ2 = 0.24, P < .001) and SFT groups neuropsychological tests of executive
one-third • Reduced parent-reported
interviewing but no skills • No between-group differences (ηρ2 range = 0.09 to 0.14, functioning for both the PML and SFT groups
have impairment compared
teaching) over 9 wk P < .001) (ηρ2 range = 0.17 to 0.19, P < .001)
comorbid with baseline for both
• No between-group • No between-group differences
conditions groups (ηρ2 = 0.08,
differences
P < .001)
• No between-group
differences
a d
A Cohen d effect size22 score of 0.2 indicates a small effect, 0.5 is a medium effect; and 0.8 is a large effect. Patients in the control group were randomized to a waiting list to receive the intervention at a later time.
A ηρ2 effect size score32 of 0.01 indicates a small effect, 0.06 is a medium effect, and 0.14 is a large effect. e
Techniques to identify or bring awareness to negative/false beliefs or automatic thoughts, and testing
b
Based on Oxford Centre for Evidence-Based Medicine criteria. or modifying them (eg, cognitive restructuring, motivational interviewing, and mindfulness).
c
Student training composed of organizational and social skills through group and individual counseling and
coaching; a behavioral point system; and parent training to reinforce skills at home. Models vary by intensity,
delivery setting, or both.

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Treatment of Attention-Deficit/Hyperactivity Disorder in Adolescents
 Treatment of Attention-Deficit/Hyperactivity Disorder in Adolescents
students in the CHP afterschool study achieved a higher GPA
(mean GPA, 2.3) at 1 year posttreatment than students in either
the CHP mentor model or community care (mean GPA of 2.1 for
both; P < .05).38
Associations of psychosocial therapies with academic impair-
ment were inconsistent. The CHP afterschool study with family
check-up improved teacher-rated (but not parent-rated) academic
impairment compared with community care (Cohen d = −0.45 vs
Cohen d = 0.1 for control group; P < .04), whereas the CHP mentor
study had no effect.35,36 Teacher-rated academic impairment did not
improve among high school students receiving CHP coaching (simi-
lar to CHP afterschool but with greater emphasis on skills training
and delivered during school hours).37 The STAND intervention led
to improved parent but not teacher ratings of academic problems
(Cohen d = 1.30; P < .05).39
Five studies32,34,38,39,41 reported associations of psychosocial
therapies with medium to large improvements in organizational skills
or executive functioning. The CHP afterschool, STAND, and HOPS
interventions were associated with significantly improved task plan-
ning, organized actions, and planner use compared with control
group (Cohen d range, 0.51-5.15).34,38,39 Participants receiving CBT
with or without additional organizational skills training signifi-
cantly improved their performance on several neuropsychological
tests of executive functioning (no difference between CBT groups).32
Parents reported reduced problems with homework or improved
homework completion among adolescents in the treatment groups
from the CHP afterschool, HOPS, and Survey, Question, Read, Write,
Recite studies compared with the control groups (between-group
Cohen d range, 0.42-0.85).32,34,38,41
Efficacy for Overall Functioning and Impairment
The associations of psychosocial treatment on improved function-
ing and impairment were modest at best. Compared with commu-
nity care, the CHP afterschool and afterschool plus family check-up
interventions were not associated with improved parent or teacher
perceptions of participants’ overall impairment.33,36 Parents of stu-
dents receiving the CHP mentor and HOPS interventions reported
improved social functioning (Cohen d range, 0.40-0.69),34,35 and
parents of students receiving the CHP coaching intervention re-
ported reduced family impairment compared with the control group
(P = .04).37 However, there were no significant associations with in-
terpersonal functioning or social skills in participants receiving either
the CHP afterschool or mentor interventions compared with com-
munity care.38 Even though adolescents receiving the STAND39 in-
tervention reported improvements in parent-teen conflict com-
pared with the control group (Cohen d = 0.65; P < .05), parents
participating in STAND and in HOPS34 did not report significant ef-
fects on the level or frequency of conflict with their child.
Discussion
Evidence suggests that both pharmacological and psychosocial treat-
ments for adolescents with ADHD are associated with improve-
ments in ADHD symptoms and related academic or organizational,
behavioral or emotional, and functional impairments. Medications
are associated with robust effects on core ADHD symptoms (over-
all evidence level of 1B based on Oxford Centre for Evidence-Based
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Review Clinical Review & Education
Medicine criteria) and psychosocial treatments are associated with
more modest benefits, with greatest benefit for ADHD-related func-
tional outcomes (overall evidence level of 2B). Even though some
RCTs assessing ADHD medications permitted participants to re-
main on psychosocial treatments (eTable 2 in the Supplement), and
many RCTs assessing psychosocial benefits for ADHD included par-
ticipants taking stable medications for ADHD (Table 4 and eTable 3
in the Supplement), there is no direct evidence to support using com-
bined medication and psychosocial treatment.
Among the FDA-approved medications for ADHD, the evi-
dence is stronger for extended-release methylphenidate and am-
phetamine formulations (2 level 1B studies for each medication based
on Oxford Centre for Evidence-Based Medicine criteria) and for ato-
moxetine (1 small level 1A meta-analysis) than for extended-
release guanfacine (1 level 1B study) or clonidine (no studies in ado-
lescents). Results of these adolescent-only studies are generally
consistent with those conducted in other age groups, although the
effective dose in adolescents may be higher than for school-aged
children.26,27,31
Evidence supports use of multicomponent psychosocial treat-
ments to improve some ADHD-related functional outcomes (1 level
1B study and multiple level 2B studies based on Oxford Centre for
Evidence-Based Medicine criteria), but not CBT as a single treat-
ment modality (2 level 1B studies). Overall, psychosocial treatments
were associated with medium to large effects on organizational
skills and inconsistent, more modest effects on parent (not
teacher) ratings of ADHD and co-occurring emotional and behav-
ioral symptoms. This is not surprising because these interventions
were designed to target ADHD-related functional and skill deficits,
such as completing homework, task planning, and self-monitoring,
rather than to address ADHD symptoms directly. In addition, con-
comitant ADHD medication treatment received by many psychoso-
cial study participants may account for the relative lack of efficacy
for ADHD symptoms.
Psychosocial interventions for adolescents have not been as
well studied as those for school-aged and younger children with
ADHD.50-54 There are few RCTs of individual psychosocial modali-
ties, and the reviewed studies of multicomponent interventions
(CHP, STAND, HOPS, and Survey, Question, Read, Write, Recite) were
not designed to distinguish the effects of individual techniques from
the rest of the treatment package. However, evidence of efficacy
from studies conducted in adolescents with conditions commonly
comorbid with ADHD (eg, substance use disorders, anxiety, and
depression),55,56 suggests that it may be reasonable to consider
adapting these techniques (motivational interviewing, mindfulness-
based CBT) for the treatment of ADHD in adolescents.
Applying results of the reviewed RCTs to everyday clinical popu-
lations, particularly in primary care, requires some caution. Medi-
cation trials were relatively brief (<13 weeks) and excluded individu-
als with diagnosed psychiatric illness, medical comorbidities,
substance use disorders, concurrent use of other psychoactive medi-
cations, and history of nonresponsiveness to ADHD medications.
Thus, participants of medication RCTs are unlikely to represent typi-
cal clinical populations of adolescents with ADHD.
On the other hand, although the psychosocial treatment
studies excluded adolescents with major mental health comor-
bidities (eg, bipolar disorder, psychosis, autism spectrum disor-
ders), many participants were permitted to have co-occurring
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 Clinical Review & Education Review Treatment of Attention-Deficit/Hyperactivity Disorder in Adolescents

Table 5. Unique Developmental Features of Adolescence and Implications for Treatment of Adolescents With Attention-Deficit/Hyperactivity
Disorder (ADHD)
Developmental Tasks
of Adolescence Presentation in Adolescents With ADHD Implications for Treatment of Adolescents With ADHD
• Poor insight into own functioning (eg, overestimating
function, underestimating effects of ADHD symptoms)
• Growing divide between perceived maturity and role • Use psychoeducational and motivational interviewing to help
Maturing cognitive
functioning relative to peers adolescents gain insight about ADHD symptoms and functioning
capacities (eg, abstract
• Poor decision making (eg, discontinuing ADHD treatment • Consider motivational interviewing or mindfulness interventions
thinking, self-reflection,
despite evidence of functional impairment) to target ambivalence about treatment and adherence
complex problem solving,
• Limited ability to sustain positive behaviors long-term • Consider adjusting the ADHD medication based on adolescent report
executive functioning)
(eg, behaviors gained due to treatment) of poor tolerability
• Increased ability to articulate negative effects
of ADHD medications
• May be increasingly identified as having a temper
Maturing • Provide support and training in conflict resolution skills
or being moody
behavioral-emotional • Explore adolescent’s peer relationships
• Increased interpersonal conflict or drama with peers;
self-regulation • Encourage mindfulness and appropriate self-care
high potential for ostracism or (cyber)bullying
Manage increase in • Easily overwhelmed by demands; secondary
complex environmental sleep disturbance • Include training interventions targeting organizational skills
demands (daily activities, • May avoid or approach multiple demands (eg, time management, materials management, approach to homework)
academics, social) in a highly disorganized fashion
Need for independence • Emphasize history from adolescents, not parents
and autonomy (healthy • Resist help from external supports at a time when support • Incorporate explicit skills teaching for self-managing ADHD medications
individuation) from is still needed (eg, self-administration, refills)
parents and other • Increased parent-adolescent conflict • Therapy to target parent-adolescent communication
authority figures and problem solving
Increased identification
with peers and • Impulsive behaviors and decision making to seek • Consider treatments that leverage positive peer role modeling
vulnerability to peer group approval or mentoring
peer pressure
• Consider behavioral contract for driving
• Consider driver training program
Managing risk-taking • Concerns about driving safety on and off
• Monitor for substance use
behaviors, including ADHD medications
• Educate about stimulant misuse or diversion; assess risk for diversion
driving and • Increased risk for substance use, stimulant misuse,
in adolescent or family
substance use and diversion
• Prescribe ADHD medications with lower abuse potential
(eg, extended-release formulations and nonstimulants)
• Screen for common psychiatric comorbidities
• Higher risk of developing comorbid psychiatric disorders
• Educate about secondary mental health disorders (eg, depression,
(eg, mood, anxiety, conduct, substance use,
anxiety, and substance use) that can arise from chronic stress
eating disorders)
• Explore and address reasons for ADHD medication reluctance
• Decline in adherence to medications and other treatments
or self-discontinuation, including adverse effects, sense of stigma,
• Need for specific, actionable, and anticipatory guidance
Other considerations perceived need
about transition to adult care, including shifting to adult
• Set target goals for transition to adult care, including self-managing
clinicians, assuming responsibility for their care, managing
ADHD medications, knowing ADHD treatment history, identifying
insurance issues, and understanding health care privacy
and making appointment with an adult ADHD clinician, identifying
laws that limit parents’ continued involvement in medical
academic, occupational, and mental health resources at college
decision making
or in the workplace

internalizing (eg, depression, anxiety) or externalizing (eg, disrup-
tive, defiant) symptoms. These co-occurring internalizing and
externalizing symptoms are common in clinical populations of
adolescents with ADHD, and participants were allowed to con-
tinue taking medications to treat ADHD. In addition, the psycho-
social treatments were often based in real-world home and
school settings. Even though psychosocial treatment study qual-
ity was generally weaker than pharmacological RCTs, the results
may be more directly applicable to the general adolescent ADHD
population.
Developmentally, adolescence is characterized by shifts in cog-
nitive capacity and behavioral-emotional regulation, as well as the
need to develop independence and autonomy while managing in-
creased environmental demands. Although many adolescents
struggle during this time, adolescents with ADHD face these devel-
opmental tasks with additional impairments that can affect their re-
sponse to ADHD treatment (Table 5).57 Adolescents with ADHD of-
ten overestimate their functioning, underestimate their difficulties,
and make poor decisions, including refusing much-needed aca-
demic and parental supports and discontinuing treatment despite
evidence of impairment. Yet ADHD treatment must target the ado-
lescent (rather than the parent) to encourage he or she to accept
treatment, learn and practice new skills, and take a central role in
making decisions (eTable 4 in the Supplement illustrates differ-
ences in treatment approach for school-aged children compared with
adolescents).
Limitations and Directions for Future Research
The paucity of high-quality studies limits our review of pharmaco-
logical and psychosocial treatments for adolescents with ADHD,
as noted by others who have conducted similar reviews.58 We ini-
tially attempted to address this by identifying RCTs that included
adolescents as part of the study sample; however, these studies
were either insufficiently powered to conduct valid analysis by
age subgroups, or incorporated age or age group as a covariate.59
We also limited the scope of this review to the treatment of non-
comorbid ADHD; however, adolescents with ADHD are more
likely to develop psychiatric comorbidities as they approach
young adulthood.60,61
This review did not attempt to address the following im-
portant and controversial aspects of ADHD treatment in adoles-
cents: (1) the interrelated concerns of addiction to stimulant

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 Treatment of Attention-Deficit/Hyperactivity Disorder in Adolescents Review Clinical Review & Education

medications,62 (2) stimulant misuse by individuals with and with-
out ADHD,63 (3) the potential risk of developing substance use
disorders and whether treatment with ADHD medication can
mitigate these risks,61,64-66 (4) the increasing off-label use of
atypical antipsychotics for youth with ADHD,12,67 or (5) the role of
mediators and moderators to better understand differential treat-
ment effects.68-70
Future ADHD research must include study participants who
are in the adolescent age range. For both pharmacological and
psychosocial interventions, studies should be designed to exam-
ine the effects of dosage, frequency, intensity, and treatment
duration upon observed clinical outcomes, including longer-term
efficacy and prevention of serious adult outcomes. Potential
moderators and mediators including ADHD severity, presence of
comorbidity, and sociodemographic variables should be investi-
gated more optimally to determine which treatments work better
for whom and why.70 In addition, future research should directly
compare the effects of combined psychosocial and pharmacologi-
cal treatments with either psychosocial or pharmacological treat-
ment alone.
Conclusions
Evidence supports the use of extended-release methylphenidate and
amphetamine formulations, atomoxetine, and extended-release gua-
nfacine to improve symptoms of ADHD in adolescents. Psychoso-
cial treatments incorporating behavior contingency management,
motivational enhancement, and academic, organizational, and so-
cial skills training techniques were associated with inconsistent ef-
fects on ADHD symptoms and greater benefit for academic and or-
ganizational skills. Additional treatment studies in adolescents,
including combined pharmacological and psychosocial treat-
ments, are needed.

ARTICLE INFORMATION
Author Contributions: Dr Chan had full access to
all of the data in the study and takes responsibility
for the integrity of the data and the accuracy of the
data analysis.
Study concept and design: All authors.
Acquisition, analysis, or interpretation of data: All
authors.
Drafting of the manuscript: All authors.
Administrative, technical, or material support:
Fogler.
Study supervision: Chan.
Conflict of Interest Disclosures: The authors have
completed and submitted the ICMJE Form for
Disclosure of Potential Conflicts of Interest. Dr Chan
reported receiving peer reviewer royalties from
UpToDate for ADHD-related content. Dr
Hammerness reported receiving royalties from
Greenwood Press for ADHD: Biographies of a
Disease, Harlequin Press/Harvard University for
Organize Your Mind, Organize Your Life, and
Massachusetts General Hospital (owner of a
copyrighted questionnaire co-developed with
Timothy Wilens, MD) licensed to Ironshore
Pharmaceuticals. No other disclosures were
reported.
Submissions: We encourage authors to submit
papers for consideration as a Review. Please
contact Edward Livingston, MD, at Edward
.livingston@jamanetwork.org or Mary McGrae
McDermott, MD, at mdm608@northwestern.edu.
REFERENCES
1. Bloom B, Jones LI, Freeman G. Summary Health
Statistics for US Children: National Health Interview
Survey, 2012. Hyattsville, MD: US Department of
Health and Human Services; 2013.
2. Barbaresi WJ, Colligan RC, Weaver AL, et al.
Mortality, ADHD, and psychosocial adversity in
adults with childhood ADHD. Pediatrics. 2013;131
(4):637-644.
3. Kessler RC, Adler L, Barkley R, et al. The prevalence
and correlates of adult ADHD in the United States. Am
J Psychiatry. 2006;163(4):716-723.
4. American Psychiatric Association. Diagnostic
and Statistical Manual of Mental Disorders. 5th ed.
Arlington, VA: American Psychiatric Publishing; 2013.
5. Wolraich ML. The Classification of Child and
Adolescent Mental Diagnoses in Primary Care:
Diagnostic and Statistical Manual for Primary Care
(DSM-PC). Elk Grove Village, IL: American Academy
of Pediatrics; 1996.
6. Adler L, Cohen J. Diagnosis and evaluation of
adults with attention-deficit/hyperactivity disorder.
Psychiatr Clin North Am. 2004;27(2):187-201.
7. Mick E, Faraone SV, Biederman J.
Age-dependent expression of attention-deficit/
hyperactivity disorder symptoms. Psychiatr Clin
North Am. 2004;27(2):215-224.
8. Brook JS, Brook DW, Zhang C, et al. Adolescent
ADHD and adult physical and mental health, work
performance, and financial stress. Pediatrics. 2013;
131(1):5-13.
9. Chan E, Zhan C, Homer CJ. Health care use and
costs for children with attention-deficit/
hyperactivity disorder. Arch Pediatr Adolesc Med.
2002;156(5):504-511.
10. Doshi JA, Hodgkins P, Kahle J, et al. Economic
impact of childhood and adult attention-deficit/
hyperactivity disorder in the United States. J Am
Acad Child Adolesc Psychiatry. 2012;51(10):990-
1002.e2.
11. Zuvekas SH, Vitiello B. Stimulant medication use
in children. Am J Psychiatry. 2012;169(2):160-166.
12. Visser SN, Bitsko RH, Danielson ML, et al.
Treatment of attention deficit/hyperactivity
disorder among children with special health care
needs. J Pediatr. 2015;166(6):1423-1430.e1, e2.
13. Wong ICK, Asherson P, Bilbow A, et al.
Cessation of Attention Deficit Hyperactivity
Disorder Drugs in the Young (CADDY). Health
Technol Assess. 2009;13(50):iii-iv, ix-xi, 1-120.
14. Wolraich M, Brown L, Brown RT, et al. ADHD:
clinical practice guideline for the diagnosis,
evaluation, and treatment of attention-deficit/
hyperactivity disorder in children and adolescents.
Pediatrics. 2011;128(5):1007-1022.
15. Pliszka S. Practice parameter for the
assessment and treatment of children and
adolescents with attention-deficit/hyperactivity
disorder. J Am Acad Child Adolesc Psychiatry. 2007;
46(7):894-921.
16. MTA Cooperative Group; Multimodal Treatment
Study of Children with ADHD. A 14-month
randomized clinical trial of treatment strategies for
attention-deficit/hyperactivity disorder. Arch Gen
Psychiatry. 1999;56(12):1073-1086.
17. Greenhill L, Kollins S, Abikoff H, et al. Efficacy
and safety of immediate-release methylphenidate
treatment for preschoolers with ADHD. J Am Acad
Child Adolesc Psychiatry. 2006;45(11):1284-1293.
18. Nutt DJ, Fone K, Asherson P, et al.
Evidence-based guidelines for management of
attention-deficit/hyperactivity disorder in
adolescents in transition to adult services and in
adults. J Psychopharmacol. 2007;21(1):10-41.
19. DuPaul GJ, Power TJ, Anastopoulos AD, Reid R.
ADHD Rating Scale IV (for Children and
Adolescents): Checklists, Norms, and Clinical
Interpretation. New York, NY: Guilford Press; 1998.
20. Goodman D, Faraone SV, Adler LA, et al.
Interpreting ADHD Rating Scale scores. Primary
Psychiatry. 2010;17(3):44-52.
21. Zhang S, Faries DE, Vowles M, Michelson D.
ADHD Rating Scale IV. Int J Methods Psychiatr Res.
2005;14(4):186-201.
22. Cohen J. Statistical Power Analysis for the
Behavioral Sciences. 2nd ed. Hillsdale, NJ: Lawrence
Erlbaum; 1988.
23. Effective Public Health Practice Project. Quality
assessment tool for quantitative studies. http:
//www.ephpp.ca/PDF/Quality%20Assessment
%20Tool_2010_2.pdf. Accessed April 14, 2016.
24. Phillips B, Ball C, Sackett D, et al. Oxford Centre
for Evidence-Based Medicine: levels of evidence.
http://www.cebm.net/oxford-centre-evidence-
based-medicine-levels-evidence-march-2009/.
Accessed September 1, 2015.
25. Spencer TJ, Wilens TE, Biederman J, et al.
Efficacy and safety of mixed amphetamine salts
extended release (Adderall XR) in the management
of attention-deficit/hyperactivity disorder in
adolescent patients. Clin Ther. 2006;28(2):266-279.
26. Wilens TE, McBurnett K, Bukstein O, et al.
Multisite controlled study of OROS
methylphenidate in the treatment of adolescents
with attention-deficit/hyperactivity disorder. Arch
Pediatr Adolesc Med. 2006;160(1):82-90.

jama.com (Reprinted) JAMA May 10, 2016 Volume 315, Number 18 2007

Copyright 2016 American Medical Association. All rights reserved.

Downloaded From: http://jama.jamanetwork.com/ by a Universite Laval User on 05/10/2016

 Clinical Review & Education Review
27. Wilens TE, Robertson B, Sikirica V, et al.
A randomized, placebo-controlled trial of
guanfacine extended release in adolescents with
attention-deficit/hyperactivity disorder. J Am Acad
Child Adolesc Psychiatry. 2015;54(11):916-925.e2.
28. Findling RL, Turnbow J, Burnside J, et al.
A randomized, double-blind, multicenter,
parallel-group, placebo-controlled,
dose-optimization study of the methylphenidate
transdermal system for the treatment of ADHD in
adolescents. CNS Spectr. 2010;15(7):419-430.
29. Findling RL, Childress AC, Cutler AJ, et al.
Efficacy and safety of lisdexamfetamine dimesylate
in adolescents with attention-deficit/hyperactivity
disorder. J Am Acad Child Adolesc Psychiatry.
2011;50(4):395-405.
30. Wietecha LA, Williams DW, Herbert M, et al.
Atomoxetine treatment in adolescents with
attention-deficit/hyperactivity disorder. J Child
Adolesc Psychopharmacol. 2009;19(6):719-730.
31. Wilens TE, Kratochvil C, Newcorn JH, Gao H.
Do children and adolescents with ADHD respond
differently to atomoxetine? J Am Acad Child Adolesc
Psychiatry. 2006;45(2):149-157.
32. Boyer BE, Geurts HM, Prins PJM, Van der Oord S.
Two novel CBTs for adolescents with ADHD. Eur
Child Adolesc Psychiatry. 2015;24(9):1075-1090.
33. Molina BSG, Flory K, Bukstein OG, et al.
Feasibility and preliminary efficacy of an
after-school program for middle schoolers with
ADHD. J Atten Disord. 2008;12(3):207-217.
34. Langberg JM, Epstein JN, Becker SP, et al.
Evaluation of the Homework, Organization, and
Planning Skills (HOPS) intervention for middle
school students with ADHD as implemented by
school mental health providers. School Psych Rev.
2012;41(3):342-364.
35. Evans SW, Serpell ZN, Schultz BK, Pastor DA.
Cumulative benefits of secondary school-based
treatment of students with attention deficit
hyperactivity disorder. School Psych Rev. 2007;36
(2):256-273.
36. Evans SW, Schultz BK, Demars CE, Davis H.
Effectiveness of the Challenging Horizons
After-School Program for young adolescents with
ADHD. Behav Ther. 2011;42(3):462-474.
37. Evans SW, Schultz BK, Demars CE.
High school–based treatment for adolescents with
attention-deficit/hyperactivity disorder. School
Psych Rev. 2014;43(2):185-202.
38. Evans SW, Langberg JM, Schultz BK, et al.
Evaluation of a school-based treatment program for
young adolescents with ADHD. J Consult Clin Psychol.
2016;84(1):15-30.
39. Sibley MH, Pelham WE, Derefinko KJ, et al.
A pilot trial of Supporting Teens’ Academic Needs
Daily (STAND). J Psychopathol Behav Assess. 2013;
35(4):436-449.
40. Vidal R, Castells J, Richarte V, et al. Group
therapy for adolescents with attention-deficit/
hyperactivity disorder. J Am Acad Child Adolesc
Psychiatry. 2015;54(4):275-282.
2008 JAMA May 10, 2016 Volume 315, Number 18 (Reprinted)
Copyright 2016 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a Universite Laval User on 05/10/2016
Treatment of Attention-Deficit/Hyperactivity Disorder in Adolescents
41. Meyer K, Kelley ML. Improving homework in
adolescents with attention-deficit/hyperactivity
disorder. Child Fam Behav Ther. 2007;29(4):25-42.
42. Maneeton N, Maneeton B, Woottiluk P, et al.
Comparative efficacy, acceptability, and tolerability
of dexmethylphenidate versus placebo in child and
adolescent ADHD. Neuropsychiatr Dis Treat. 2015;
11:2943-2952.
43. Hodgkins P, Shaw M, McCarthy S, Sallee FR.
The pharmacology and clinical outcomes of
amphetamines to treat ADHD. CNS Drugs. 2012;26
(3):245-268.
44. Maneeton B, Maneeton N, Likhitsathian S,
et al. Comparative efficacy, acceptability, and
tolerability of lisdexamfetamine in child and
adolescent ADHD. Drug Des Devel Ther. 2015;9:
1927-1936.
45. Sallee F, Connor DF, Newcorn JH. A review
of the rationale and clinical utilization of
α2-adrenoceptor agonists for the treatment
of attention-deficit/hyperactivity and related
disorders. J Child Adolesc Psychopharmacol. 2013;
23(5):308-319.
46. Hirota T, Schwartz S, Correll CU. Alpha-2
agonists for attention-deficit/hyperactivity disorder
in youth. J Am Acad Child Adolesc Psychiatry. 2014;
53(2):153-173.
47. Spencer TJ, Greenbaum M, Ginsberg LD,
Murphy WR. Safety and effectiveness of
coadministration of guanfacine extended release
and psychostimulants in children and adolescents
with attention-deficit/hyperactivity disorder. J Child
Adolesc Psychopharmacol. 2009;19(5):501-510.
48. Biederman J, Melmed RD, Patel A, et al.
A randomized, double-blind, placebo-controlled
study of guanfacine extended release in children
and adolescents with attention-deficit/
hyperactivity disorder. Pediatrics. 2008;121(1):e73-
e84.
49. Childress AC, Sallee FR. Attention-deficit/
hyperactivity disorder with inadequate response to
stimulants. CNS Drugs. 2014;28(2):121-129.
50. Evans SW, Owens JS, Bunford N.
Evidence-based psychosocial treatments for
children and adolescents with attention-deficit/
hyperactivity disorder. J Clin Child Adolesc Psychol.
2014;43(4):527-551.
51. Evans SW, Langberg JM, Egan T, Molitor SJ.
Middle school-based and high school-based
interventions for adolescents with ADHD. Child
Adolesc Psychiatr Clin N Am. 2014;23(4):699-715.
52. Daley D, van der Oord S, Ferrin M, et al.
Behavioral interventions in attention-deficit/
hyperactivity disorder. J Am Acad Child Adolesc
Psychiatry. 2014;53(8):835-847, e1-e5.
53. Sonuga-Barke EJS, Brandeis D, Cortese S, et al.
Nonpharmacological interventions for ADHD. Am J
Psychiatry. 2013;170(3):275-289.
54. Fabiano GA, Schatz NK, Aloe AM, et al.
A systematic review of meta-analyses of
psychosocial treatment for attention-deficit/
hyperactivity disorder. Clin Child Fam Psychol Rev.
2015;18(1):77-97.
55. Lundahl B, Burke BL. The effectiveness and
applicability of motivational interviewing. J Clin
Psychol. 2009;65(11):1232-1245.
56. Hofmann SG, Sawyer AT, Witt AA, Oh D.
The effect of mindfulness-based therapy on anxiety
and depression. J Consult Clin Psychol. 2010;78(2):
169-183.
57. Turgay A, Goodman DW, Asherson P, et al.
Lifespan persistence of ADHD. J Clin Psychiatry.
2012;73(2):192-201.
58. Sibley MH, Kuriyan AB, Evans SW, et al.
Pharmacological and psychosocial treatments for
adolescents with ADHD. Clin Psychol Rev. 2014;34
(3):218-232.
59. Zwi M, Jones H, Thorgaard C, et al. Parent
training interventions for attention deficit
hyperactivity disorder (ADHD) in children aged 5 to
18 years. Cochrane Database Syst Rev. 2011;(12):
CD003018.
60. Yoshimasu K, Barbaresi WJ, Colligan RC, et al.
Childhood ADHD is strongly associated with a
broad range of psychiatric disorders during
adolescence. J Child Psychol Psychiatry. 2012;53
(10):1036-1043.
61. Lee SS, Humphreys KL, Flory K, et al.
Prospective association of childhood
attention-deficit/hyperactivity disorder (ADHD)
and substance use and abuse/dependence. Clin
Psychol Rev. 2011;31(3):328-341.
62. Volkow ND, Swanson JM. Variables that affect
the clinical use and abuse of methylphenidate in the
treatment of ADHD. Am J Psychiatry. 2003;160(11):
1909-1918.
63. Benson K, Flory K, Humphreys KL, Lee SS.
Misuse of stimulant medication among college
students. Clin Child Fam Psychol Rev. 2015;18(1):50-
76.
64. Humphreys KL, Eng T, Lee SS. Stimulant
medication and substance use outcomes. JAMA
Psychiatry. 2013;70(7):740-749.
65. Harstad E, Levy S. Attention-deficit/
hyperactivity disorder and substance abuse.
Pediatrics. 2014;134(1):e293-e301.
66. Groenman AP, Oosterlaan J, Rommelse NNJ,
et al. Stimulant treatment for attention-deficit
hyperactivity disorder and risk of developing
substance use disorder. Br J Psychiatry. 2013;203
(2):112-119.
67. Olfson M, King M, Schoenbaum M. Treatment
of young people with antipsychotic medications in
the United States. JAMA Psychiatry. 2015;72(9):
867-874.
68. Owens EB, Hinshaw SP, Kraemer HC, et al.
Which treatment for whom for ADHD. J Consult Clin
Psychol. 2003;71(3):540-552.
69. Hinshaw SP. Moderators and mediators of
treatment outcome for youth with ADHD. J Pediatr
Psychol. 2007;32(6):664-675.
70. Bloch MH. Meta-analysis and moderator
analysis. J Am Acad Child Adolesc Psychiatry. 2014;
53(2):135-137.
jama.com