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American Academy of Pediatrics
ELECTRONIC ARTICLE

Treatment of Attention-Deficit/Hyperactivity Disorder: Overview of the Evidence

Ronald T. Brown, Robert W. Amler, Wendy S. Freeman, James M. Perrin, Martin T. Stein, Heidi M. Feldman, Karen Pierce, Mark L. Wolraich and ; and the Committee on Quality Improvement, Subcommittee on Attention-Deficit/Hyperactivity Disorder
Pediatrics June 2005, 115 (6) e749-e757; DOI: https://doi.org/10.1542/peds.2004-2560
Ronald T. Brown
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Robert W. Amler
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Wendy S. Freeman
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James M. Perrin
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Martin T. Stein
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Heidi M. Feldman
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Karen Pierce
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Mark L. Wolraich
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Abstract

The American Academy of Pediatrics' Committee on Quality Improvement, Subcommittee on Attention-Deficit/Hyperactivity Disorder, reviewed and analyzed the current literature for the purpose of developing an evidence-based clinical practice guideline for the treatment of the school-aged child with attention-deficit/hyperactivity disorder (ADHD). This review included several key reports, including an evidence review from the McMaster Evidence-Based Practice Center (supported by the Agency for Healthcare Research and Quality), a report from the Canadian Coordinating Office for Health Technology Assessment, the Multimodal Treatment for ADHD comparative clinical trial (supported by the National Institute of Mental Health), and supplemental reviews conducted by the subcommittee. These reviews provided substantial information about different treatments for ADHD and their efficacy in improving certain characteristics or outcomes for children with ADHD as well as adverse effects and benefits of multiple modes of treatment compared with single modes (eg, medication or behavior therapies alone). The reviews also compared the effects of different medications.

Other evidence documents the long-term nature of ADHD in children and its classification as a chronic condition, meriting the application of general concepts of chronic-condition management, including an individual treatment plan with a focus on ongoing parent and child education, management, and monitoring. The evidence strongly supports the use of stimulant medications for treating the core symptoms of children with ADHD and, to a lesser degree, for improving functioning. Behavior therapy alone has only limited effect on symptoms or functioning of children with ADHD, although combining behavior therapy with medication seems to improve functioning and may decrease the amount of (stimulant) medication needed. Comparison among stimulants (mainly methylphenidate and amphetamines) did not indicate that 1 class outperformed the other.

  • attention-deficit hyperactivity disorder
  • stimulant medication
  • multimodal treatment
  • behavior management
  • co-occurring

INTRODUCTION

The American Academy of Pediatrics' (AAP) Committee on Quality Improvement, Subcommittee on Attention-Deficit/Hyperactivity Disorder, developed a clinical practice guideline pertaining to the treatment of school-aged children with attention-deficit/hyperactivity disorder (ADHD).1,2 The review here covers the additional evidence gathered for and by the subcommittee regarding specific treatments for ADHD. It does not include more recent studies published since the publication of the guideline in 2001. Other evidence supports the notion that ADHD is a chronic health condition meriting the application of general principles of management of childhood chronic conditions by primary care clinicians. Longitudinal studies of Barkley et al3 and Biederman et al4 document the persistence of the condition over time. Previous policy statements by the AAP describe the elements of chronic-condition care, including educating parents and children about illness, developing individual treatment plans, helping to coordinate multiple services, and encouraging parents to have contact with other parents of children with chronic conditions. Because ADHD has pervasive effects on the child's daily life, including school performance, a partnership of clinicians and school personnel will help ensure the child's best progress and proper assessment of progress.

This report summarizes the empirical literature on which the practice guideline's recommendation for pharmacologic and/or behavioral intervention was based. Certain other aspects of clinical care have not been the focus of careful clinical trials or randomized, controlled studies to determine accurately optimal practices. Thus, many of these recommendations reflect consensus of best practices. The specific areas included in these consensus recommendations include (1) the best specific ways of titrating a child's medications, (2) the frequency of monitoring visits during titration phases and after stabilization, or (3) the specific content of monitoring. Again, these recommendations reflect assessment of best practices in long-term care.

Four main sources of data were examined in developing these treatment recommendations. The McMaster University Evidence-Based Practice Center (under contract with the Agency for Healthcare Research and Quality and in partnership with the AAP and other organizations) reviewed the short- and long-term efficacy and safety of pharmacologic and nonpharmacologic interventions for ADHD and the comparative efficacy of single versus combined treatments. For a full account of the evidence, see the technical report compiled by the former Agency for Health Care Policy and Research (now the Agency for Healthcare Research and Quality).5 The second source was a review of interventions for ADHD conducted by the Center for Community Health Research, British Columbia Research Institute for Children's and Women's Health, and the University of British Columbia6 for the Canadian Coordinating Office of Health Technology Assessment. The third source included the findings from the multisite treatment study conducted by the Multimodal Treatment Study for Children With ADHD (the MTA Cooperative Group),7,8 which is supported by the National Institute of Mental Health.

After reviewing the findings and conclusions of the 3 sources listed above, the subcommittee conducted an additional search of the available literature to assess further the effectiveness of behavioral interventions both as stand-alone regimens and in combination with pharmacologic treatments. This search selected published reports of trials of behavior therapies in groups of school-aged children with ADHD. Individual case reports were excluded. The evidence from this search was compiled and evaluated by the subcommittee.

McMASTER UNIVERSITY EVIDENCE-BASED PRACTICE CENTER REVIEW

The goals of the evidence-based review conducted by the McMaster University Evidence-Based Practice Center Group5 were to examine the efficacy of nonstimulant medications and nonpharmacologic interventions for ADHD in children and adults and to examine the comparative efficacy of combined versus individual interventions. The technical review examined (1) drug-to-drug comparisons of specific stimulant medications, (2) stimulants versus antidepressant medications, and (3) comparisons of different forms of the same medication. The stimulant drugs examined were methylphenidate (MPH), dexedrine (DEX), and pemoline (PEM). The review also compared tricyclic antidepressants versus placebo and pharmacologic versus nonpharmacologic interventions. The report also examined long-term studies with a duration of 12 or more weeks. Final categories reviewed were studies examining the treatment of ADHD in adults, treatment combinations, and the adverse effects of pharmacologic interventions. This article reviews only findings pertaining to treatment of ADHD among school-aged children.

The McMaster review selected a total of 92 empirical articles reflecting 78 investigations from a pool of 2405 citations compiled from traditional databases (Medline, Cinahl, HealthStar, PsychINFO, Embase), The Cochrane Library (1997, issue 4), reference lists of articles identified in the previous sources, and additional citations suggested by members of the McMaster research team and partnering organizations. Two reviewers independently rated each article to determine the quality of the methodology used in the study. Studies were included in the evidence-based review if they were randomized, controlled trial (RCTs), involved human subjects, and were published as a full report in a peer-reviewed journal. Studies that included participants with diagnoses other than ADHD (eg, oppositional defiant disorder, conduct disorder) were included in the review only if the study provided a separate analysis for the study participants with ADHD.

A problem identified by the review team and associated organizations was the diversity of outcomes used in these many studies. Some studies used indicators or core symptoms of ADHD; others examined aspects of school or social behavior or behaviors at home. This diversity makes clear comparisons among treatment regimens difficult. The McMaster review noted important methodologic limitations in the numerous studies examining interventions for ADHD spanning a period of more than 25 years. Major limitations included small sample sizes and the use of heterogeneous outcome measures. The review found few studies in most of the study areas.

Drug-to-Drug Comparisons

Twenty-three studies on specific drug-to-drug comparisons were included in the review. These included studies comparing different stimulant medications: 8 studies compared MPH and DEX,9–17 2 compared MPH and PEM,18,19 and 1 compared DEX and PEM.20 Three studies compared a stimulant drug and a tricyclic antidepressant. One study compared MPH and desipramine,21 and 2 compared MPH and imipramine.22,23 Also included were studies comparing different formulations of the same drug. Three studies compared regular and sustained-release formulations of MPH,24–26 and 1 study compared different isomers of MPH (l-MPH versus d-MPH).27 Finally, 1 study compared DEX and levoamphetamine.9

The stimulant-stimulant comparisons documented few, if any, differences among MPH, DEX, and PEM. Findings from the 3 reviewed studies comparing a stimulant medication with a tricyclic antidepressant medication were inconclusive. The study comparing MPH and desipramine21 included children with symptoms of both ADHD and depression. MPH outperformed desipramine in improving children's vigilance and ability-to-learn paired associations. Of the 2 studies comparing MPH and imipramine, 1 found no significant differences, and the other provided data favoring imipramine compared with MPH.22,23 Finally, the studies comparing different formulations of the same drug revealed no significant formulation effects.

Tricyclic Antidepressants Versus Placebo

Nine reviewed studies compared the efficacy of tricyclic antidepressant medication and placebo in managing symptoms of ADHD. Six studies (described in a total of 8 reports) examined the effects of desipramine,21,28–34 and all of the studies revealed improvements for children taking desipramine when compared with placebo. Three studies examined the efficacy of imipramine23,35,36 and reported inconsistent findings, with improved performance on some tasks and behavior measures but not others.

The studies showed that desipramine is more effective than placebo despite the small sample sizes and heterogenous designs. Results were inconsistent for studies comparing imipramine with placebo. The McMaster report suggests the need for more research to determine the role of these drugs for the treatment of ADHD.

Pharmacologic Versus Nonpharmacologic Interventions

Six reviewed studies compared pharmacologic versus nonpharmacologic interventions. Five studies compared some form of psychological or behavioral intervention versus medication,6,7,37–40 and 1 study compared DEX and the dietary supplement Efamol (Efamol Ltd, North Yorkshire, United Kingdom).41 The evidence review noted that these studies, with the exception of the study by the MTA Cooperative Group, provided insufficient detail regarding the interventions and methodology and much heterogeneity in the type of nondrug intervention and outcomes assessed. The MTA Cooperative Group provided much more detail regarding its clinical interventions and outcome measures. Because this study was well designed, had a large sample, and provided a rich source of information, findings from the MTA Cooperative Group study are reviewed in a separate section of this article.

Combined Interventions

The McMaster team found 20 studies satisfactory to review to determine the benefits of combined interventions over and above the effects of single interventions. Five studies compared drug combinations (ie, MPH combined with either amphetamine, caffeine, desipramine, or haloperidol) and a single stimulant medication.42,43 Fourteen studies involved comparisons of either behavior or cognitive therapy along with combined nonpharmacologic intervention and stimulant medication.7,8,37–39,44–54 None of these studies, with the exception of that by Carlson et al,47 provided evidence to suggest that nonpharmacologic intervention alone performed as well as the nonpharmacologic intervention plus stimulant medication.

Long-Term Intervention for ADHD

The McMaster report reviewed available studies that examined the effects of long-term intervention for ADHD. Even with a definition of “long-term intervention” as a treatment administered for 12 or more weeks, only 14 studies were found for review.* The review concluded that, regardless of treatment, there was an overall trend for improvement over time as long as the treatment is continued, indicating the importance of treatment adherence.

Adverse Effects of Pharmacotherapy for ADHD

The McMaster group also reviewed 33 reports based on 28 RCTs and 1 nonrandomized study to evaluate the adverse effects of pharmacotherapy. Nearly two thirds of the reports evaluated adverse effects for less than 12 weeks, and in many of the studies, sample sizes were small (ie, 30 or fewer participants). Most (n = 15) studies focused on MPH. Nine examined amphetamines (DEX or l-amphetamine); 2 examined PEM; and 2 examined antidepressants. Across studies, the most frequently examined adverse effects were appetite suppression, sleep disturbances, headaches, motor tics, abdominal pain, irritability, nausea, and fatigue. The report concluded that, overall, many of the adverse effects associated with the use of stimulant medications in the management of ADHD symptoms seem to be mild, of short duration, and responsive to dosing or timing adjustments. However, it should be noted that RCTs are not a sufficient source for the determination of rare adverse effects such as liver failure in PEM use.

The McMaster review found few, if any, differences across different stimulants (MPH, DEX, PEM). However, it made no conclusions regarding the relative effectiveness of stimulants versus tricyclic antidepressant medications in managing ADHD symptoms. The review concluded that stimulant medication outperforms nonpharmacologic interventions in controlling the core symptoms of ADHD but provided insufficient information to conclude whether drug combinations outperform stimulant medications alone or that nonpharmacologic intervention adds to pharmacologic intervention. They noted a need for more definitive studies examining the value of combination treatments, studies that will require significant resources and collaboration and more complex study designs. One such study, the MTA Cooperative Group study, is reviewed later in this technical report.

A report of the Canadian Coordinating Office for Health Technology Assessment6 reviewed empirical evidence addressing several issues pertaining to the treatment of ADHD. The report addressed the efficacy of MPH, the efficacy of psychological/behavioral treatments for ADHD, comparisons between MPH and other stimulant medications, comparisons between MPH and psychological/behavioral treatments, and comparisons between combined drug and psychological/behavioral treatments for ADHD.

This review considered 195 treatment studies from a pool of more than 1000 citations from articles published after 1980 compiled from traditional databases (Medline, Current Contents, HealthStar, PsychINFO, First Search, CUE, Embase), selected reference lists, and published and unpublished studies made available by pharmaceutical manufacturers. Studies were included in the review if they were RCTs involving either parallel group designs or within-subjects crossover designs with participants randomly assigned to treatment order, involved children 18 years or younger, and involved children with ADHD who were unselected for the presence of specific coexisting disorders (ie, the presence of coexisting disorders were acceptable if the study did not focus on the effects of intervention on a specific ADHD subpopulation as defined by a particular coexisting condition). These strict criteria allowed inclusion of only 26 of the 195 articles for full review, including 21 drug studies, 2 psychological/behavioral studies,55,61 and 3 studies of combined drug and psychological/behavioral treatment.37,45,62 Among the drug studies, posttreatment assessments generally were conducted between 7 and 25 days after the onset of pharmacologic intervention and at a time when the child was still receiving medication. The 5 studies examining either psychological/behavioral interventions or psychological/behavioral interventions combined with pharmacotherapy included both posttreatment assessments 70 to 120 days after the initiation of treatment and follow-up assessments ranging from 112 to 365 days after initiation of treatment.

For comparisons across trials, the report used the hyperactivity index of the Conners' Teacher Rating Scale and Conners' Parent Rating Scale63,64 to avoid interpretational difficulties that occur as a result of examination of heterogeneous outcome measures across studies. This point is discussed further in the section (“Multi-Modal Treatment Study of Children with ADHD”) describing findings from the MTA Cooperative Group study.

Stimulant Medication

A body of evidence attested to the efficacy of MPH in treating the symptoms of ADHD.6 Of the 34 studies reviewed involving MPH, 15 focused on the elementary school–aged population, with few studies among preschoolers (n = 6) and adolescents (n = 13). Only the findings pertaining to school-aged children are discussed in this technical report.

MPH improved functioning in a number of other domains, at least in the short term. However, the effect sizes varied among symptom domains, with the strongest effects of stimulant medication on measures of attention, distractibility, and impulsivity (effect sizes: 0.75–0.84; mean: 0.78) and observable social and classroom behavior (effect sizes: 0.63–0.85; mean: 0.81). Only modest effects were reported for academic achievement (effect sizes: 0.19–0.47; mean: 0.34).

Direct comparisons of different stimulant medications revealed no clear differences among MPH, DEX, and PEM. Two studies examining the efficacy of psychological/behavioral treatments compared with a control group revealed inconsistent findings. One study showed significant treatment effects when considering parent reports of ADHD symptoms on the Revised Behavioral Problems Checklist,65 although this checklist was not identified as one of the acceptable outcome measures as determined by the Centre for Health Evaluation Research.55 The other study used the Conners' Teacher Rating Scale and showed no treatment effects.61

Combined Interventions

Three studies addressed combined medical and psychological/behavioral therapy with inconclusive results.37,62

Overall, this review concluded that evidence consistently supports the efficacy of drug therapy in managing the core symptoms of ADHD, with no clear differences among MPH, DEX, and PEM. However, the ability to make comparisons among these drug treatments was limited by the few data available for medications other than MPH at the time of the review. Psychological/behavioral therapies without medication treatment were not efficacious in managing the core symptoms of ADHD. Combined therapy did not outperform medication alone, at least when examining core ADHD symptoms. Finally, Miller et al6 reported that findings were inconsistent with regard to the benefit of combining psychological/behavioral therapies with medication versus psychological/drug therapy alone, with combined therapies seeming more efficacious when considering the ratings of the parent, but not of the teacher, for ADHD symptoms. Again, conclusions are limited by the paucity of well-controlled studies, the small number of participants in those studies, and the assessment of treatment effects focusing on the core symptoms of ADHD as captured by a narrow selection of behavior ratings scales.

MULTIMODAL TREATMENT STUDY OF CHILDREN WITH ADHD

The National Institute of Mental Health Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder7,8,66 included 579 children with ADHD (combined subtype) who were assigned randomly to 1 of 4 treatment groups: state-of-the-art medication management, intensive behavioral intervention, a combination of the 2 interventions, and a community treatment control group who received “usual care” (most commonly medication). Outcomes were assessed in multiple domains and included measures reflecting the core symptoms of ADHD as well as measures of co-occurring problems in social skills, parent-child relations, oppositional defiant behavior, internalizing behavior problems (eg, anxiety), and academic achievement. Outcome data reflected assessments conducted while children in groups involving pharmacotherapy were still receiving medication, although the behavioral interventions in the behavioral and combined treatment groups had been completed.

In terms of treatment outcome, all 4 treatment groups showed improvements over time, with medication management and the combined intervention associated with greater improvement than the intensive behavioral intervention alone and the community treatment control group, when considering the core symptoms of ADHD.7,8,66 However, only families assigned to the combined treatment group showed consistently greater benefits than the families in the community treatment group across other outcomes domains (eg, disruptive behavior, parent-child relations, social skills).7,8,66 Children with ADHD who had coexisting anxiety disorders responded well in both of the treatment groups that included the intensive behavioral interventions.67,68

Treatment outcome was also examined against a broad composite outcome measure that aggregated treatment responses across a broad array of symptom and functional domains including internalizing (ie, anxiety, depression) and externalizing (opposition, aggression) symptomatology and social skills.69 The investigators added this analysis to address the concern that measures that assess primarily core symptoms of ADHD may be less sensitive to the effects of behavioral intervention. Using this composite measure as an outcome variable, analyses revealed that children who received the combined intervention exhibited the best treatment response.69

Wells et al70 examined the effect of treatment on parent and family stress measures. Data revealed no differences among the 3 study treatment groups and the community treatment control group on measures of family distress (eg, parenting stress, depressive symptoms among parents, marital adjustment). However, compared with the community treatment control group, parents in the medication management, intensive behavioral intervention, and combined treatment groups reported greater reductions in their use of negative or ineffective discipline.70 Data were also examined to determine if such parent-reported changes in parenting behavior were associated with teachers' reports of child behavior at the end of treatment.71 Findings revealed that, at the end of treatment, teachers' ratings of disruptive child behavior fell within the normal range for families that participated in the combined treatment group, and this group reported the greatest reductions in negative and ineffective discipline. This effect was not found for families who participated in behavioral intervention alone.

One component of the intensive behavioral intervention arm of the MTA Cooperative Group study was a summer treatment program. Pelham et al72 evaluated 117 children participating in a summer program at 3 of the MTA Cooperative Group sites. Approximately half of these children were assigned to the behavior intervention alone group and half were assigned to the combined treatment group. Children in the behavioral summer program who were also medicated showed a better response to treatment on 5 measures (following rules, good sportsmanship, peer negative nominations, and summer program teacher ratings of ADHD symptoms). However, children responded similarly to treatment regardless of medication status on 30 other measures. For 6 of the 35 measures of child behavior, children in the combined treatment group were more likely than those in the behavioral treatment alone group to fall within the normative range.72

ADDITIONAL SUBCOMMITTEE SEARCH AND REVIEW

The goal of the additional literature search was to identify additional investigational evidence to quantify the effectiveness of behavioral treatment in combination with drug treatment. This review originally provided ∼200 potentially relevant articles, most of which were already included in other sources of information. After excluding case reports and general review articles, the subcommittee formally reviewed 28 articles and included 12 articles of relevance that had not been cited previously in other reviews.45,47,51,72–79 Table 1 summarizes the evidence of these reviews. The subcommittee assessed the additional evidence obtained from this review and noted an imbalance in the quality of evidence available for drugs versus behavioral interventions. Although drug regimens were highly specific as to type of drug, dose, and duration of treatment, behavioral interventions lacked this specificity and were less quantified. Investigators did not use identical behavioral interventions and used varying degrees of detail to describe the interventions.† The subcommittee found diversity in the type, intensity, and duration of interventions; for example, some focused on the family setting, and others focused on the school setting. No data directly compared the benefits of these different modalities, such as comparing daily report cards and summer training programs. The costs of these programs varied widely. Subcommittee members noted that these factors made it unlikely that a strong evidence-based recommendation for behavioral intervention per se would be possible.

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TABLE 1.

Review of Interventions for ADHD

The subcommittee concluded, on the basis of data from this additional literature review, that drug treatment alone showed a consistent dose-sensitive effect in improving the core symptoms of ADHD. Behavioral interventions alone did not demonstrate statistically significant results. Medication treatment in combination with behavioral interventions was shown to be as beneficial as drug treatment alone. In addition, some studies found that combined modalities yielded 2 additional desirable outcomes: (1) they enhanced teacher and parent acceptance, and (2) they lowered the drug doses needed to achieve the same therapeutic benefits as with drug treatment alone.47

CONCLUSIONS

ADHD is a chronic condition that requires ongoing management and monitoring. A robust evidence base attests to the efficacy of stimulant medications in helping to manage the symptoms of ADHD among school-aged children. The stimulant drugs tested seemed equally effective. Tricyclic antidepressants may be effective also but are recommended only when children have been refractory to 2 or more stimulant drugs or have intolerable adverse effects. When considering evidence from RCTs, the data in support of behavioral intervention are less compelling. None of the nonpharmacologic interventions tested were more effective than medication in treating the symptoms of ADHD. Long-standing clinical experience dictates that education and counseling of the patient, family, and school personnel are valuable and necessary adjuncts to drug therapy, as with most long-term treatments for chronic conditions.

ADDENDUM

Atomoxetine is a nonstimulant licensed by the Food and Drug Administration in November 2002 for the treatment of ADHD in children and adolescents.80 It is a selective inhibitor of the presynaptic norepinephrine transporter in the central nervous system. Atomoxetine increases both norepinephrine and dopamine levels, especially in the prefrontal cortex. In a randomized, placebo-controlled trial in children and adolescents 8 to 18 years of age over an 8-week period, atomoxetine demonstrated a statistically significant reduction in core ADHD symptoms and improvement in social and family functioning compared with the placebo group.81 Atomoxetine was compared with MPH in a randomized, open-label trial in children with ADHD during a 10-week study period. Significant improvements in inattentive and hyperactive/impulsive symptom domains were similar with both medications when assessed by parents and clinicians. Adverse effects were also similar (appetite suppression, initial weight loss), with the exception that atomoxetine does not cause or worsen insomnia but in the early phase can cause drowsiness.82 Atomoxetine treatment was associated with small but statistically significant increases in mean systolic pressure in adults and diastolic pressure in children and adolescents.83 Blood pressure and pulse tended to increase early in therapy, then stabilized, and returned toward baseline after drug discontinuation. There was no significant difference as revealed by electrocardiogram between atomoxetine and placebo groups in change in QT interval for all study populations. Discontinuations because of cardiovascular-related events did not occur in the child/adolescent group.

Atomoxetine has a slower onset to action than do stimulants; thus, effects may not be seen until the end of the first week of treatment, but atomoxetine seems to have a longer duration of action after a once-a-day dose with suggestions of symptom relief during the evening and early-morning hours. The treatment effect size (0.71) for core ADHD symptoms is similar when once-daily dosing is compared with twice-daily dosing, and parent ratings document a sustained effect late in the day.84 Motor and verbal tics associated with atomoxetine have not been reported.

Committee on Quality Improvement, 1999–2000

Charles J. Homer, MD, MPH, Chairperson

Richard D. Baltz, MD

Gerald B. Hickson, MD

Paul V. Miles, MD

Thomas B. Newman, MD, MPH

Joan E. Shook, MD

William M. Zurhellen, MD

Liaisons

Betty A. Lowe, MD

National Association of Children's Hospitals and Related Institutions

Ellen Schwalenstocker, MBA

National Association of Children's Hospitals and Related Institutions

Michael J. Goldberg, MD

Council on Sections

Richard Shiffman, MD

Section on Computers and Other Technologies

Jan Ellen Berger, MD

Committee on Medical Liability

F. Lane France, MD

Committee on Practice and Ambulatory Medicine

Subcommittee on Attention-Deficit/Hyperactivity Disorder

James M. Perrin, MD, Co-chairperson

Martin T. Stein, MD, Co-chairperson

Robert W. Amler, MD

Thomas A. Blondis, MD

Heidi M. Feldman, MD, PhD

Bruce P. Meyer, MD

Bennett A. Shaywitz, MD

Mark L. Wolraich, MD

Consultants

Anthony DeSpirito, MD

Charles J. Homer, MD, MPH

Wendy S. Freeman, PhD

Liaisons

Karen Pierce, MD

American Academy of Child and Adolescent Psychiatry

Theodore G. Ganiats, MD

American Academy of Family Physicians

Brian Grabert, MD

Child Neurology Society

Ronald T. Brown, PhD

Society for Pediatric Psychology

Footnotes

  • ↵* Refs 7, 8, 15, 22, 37–39, 45, 46, and 55–60.

  • ↵† Typically, medication trials provide an easier task for researchers, insofar as the intervention can be highly and tightly specified. Most other interventions (eg, physical therapy for arthritis, cognitive therapies for mental health conditions, rehabilitation for stroke, behavior therapies for ADHD) all have difficulty with much less specificity and exactness in specifying the intervention. This problem in specificity means that for most conditions, medications will have a stronger evidence base.

AAP, American Academy of Pediatrics • ADHD, attention-deficit/hyperactivity disorder • MTA, Multimodal Treatment Study for Children With ADHD • MPH, methylphenidate • DEX, dexedrine • PEM, pemoline • RCT, randomized, controlled trial

REFERENCES

  1. ↵
    American Academy of Pediatrics, Committee on Quality Improvement, Subcommittee on Attention-Deficit/Hyperactivity Disorder. Clinical practice guideline: diagnosis and evaluation of the child with attention-deficit/hyperactivity disorder. Pediatrics.2000;105 :1158– 1170
    OpenUrlAbstract/FREE Full Text
  2. ↵
    American Academy of Pediatrics, Committee on Quality Improvement, Subcommittee on Attention-Deficit/Hyperactivity Disorder. Clinical practice guideline: treatment of the school-aged child with attention-deficit/hyperactivity disorder. Pediatrics.2001;108 :1033– 1044
    OpenUrlAbstract/FREE Full Text
  3. ↵
    Barkley RA, Fischer M, Edelbrock CS, Smallish L. The adolescent outcome of hyperactive children diagnosed by research criteria: I. An 8-year prospective follow-up study. J Am Acad Child Adolesc Psychiatry.1990;29 :546– 557
    OpenUrlCrossRefPubMed
  4. ↵
    Biederman J, Faraone S, Milberger S, et al. A prospective 4-year follow-up study of attention-deficit hyperactivity and related disorders. Arch Gen Psychiatry.1996;53 :437– 446
    OpenUrlCrossRefPubMed
  5. ↵
    McMaster University Evidence-Based Practice Center. Treatment of Attention-Deficit Hyperactivity Disorder. Rockville, MD: Agency for Health Care Policy and Research; 1999. Evidence Report/Technology Assessment no. 11, AHCPR Publication no. 99-E018
  6. ↵
    Miller A, Lee SK, Raina P, Klassen A, Zupancic J, Olsen L. A review of therapies for attention-deficit/hyperactivity disorder. Ottawa, Canada: Canadian Coordinating Office for Health Technology Assessment; 1998
  7. ↵
    The 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 :1073– 1086
    OpenUrlCrossRefPubMed
  8. ↵
    Taylor E. Development of clinical services for attention-deficit/hyperactivity disorder. Arch Gen Psychiatry.1999;56 :1097– 1099
    OpenUrlCrossRefPubMed
  9. ↵
    Arnold LE, Huestis RD, Smeltzer DJ, Scheib J, Wemmer D, Colner G. Levoamphetamine vs dextroamphetamine in minimal brain dysfunction. Replication, time response, and differential effect by diagnostic group and family rating. Arch Gen Psychiatry.1976;33 :292– 301
    OpenUrlCrossRefPubMed
  10. Borcherding BG, Keysor CS, Cooper TB, Rapoport JL. Differential effects of methylphenidate and dextroamphetamine on the motor activity level of hyperactive children. Neuropsychopharmacology.1989;2 :255– 263
    OpenUrlCrossRefPubMed
  11. Castellanos FX, Giedd JN, Elia J, et al. Controlled stimulant treatment of ADHD and comorbid Tourette's syndrome: effects of stimulant and dose. J Am Acad Child Adolesc Psychiatry.1997;36 :589– 596
    OpenUrlCrossRefPubMed
  12. Efron D, Jarman F, Barker M. Methylphenidate versus dexamphetamine in children with attention deficit hyperactivity disorder: a double-blind, crossover trial. Pediatrics.1997;100 (6). Available at: www.pediatrics.org/cgi/content/full/100/6/e6
  13. Elia J, Borcherding BG, Rapoport JL, Keysor CS. Methylphenidate and dextroamphetamine treatments of hyperactivity: are there true nonresponders? Psychiatry Res.1991;36 :141– 155
    OpenUrlCrossRefPubMed
  14. Gross MD. A comparison of dextro-amphetamine and racemic-amphetamine in the treatment of the hyperkinetic syndrome of minimal brain dysfunction. Dis Nerv Syst.1976;37 :14– 16
    OpenUrlPubMed
  15. ↵
    Kupietz SS, Winsberg BG, Richardson E, Matinsky S, Mendell N. Effects of methylphenidate dosage in hyperactive reading-disabled children: I. Behavior and cognitive performance effects. J Am Acad Child Adolesc Psychiatry.1988;27 :70– 77
    OpenUrlCrossRefPubMed
  16. Matochik JA, Liebenauer LL, King C, Szymanski HV, Cohen RM, Zametkin AJ. Cerebral glucose metabolism in adults with attention deficit hyperactivity disorder after chronic stimulant treatment. Am J Psychiatry.1994;151 :658– 664
    OpenUrlPubMed
  17. ↵
    Winsberg BG, Press M, Bailer I, Kupietz S. Dextroamphetamine and methylphenidate in the treatment of hyperactive-aggressive children. Pediatrics.1974;53 :236– 241
    OpenUrlAbstract/FREE Full Text
  18. ↵
    Conners CK, Taylor E. Pemoline, methylphenidate, and placebo in children with minimal brain dysfunction. Arch Gen Psychiatry.1980;37 :922– 930
    OpenUrlCrossRefPubMed
  19. ↵
    Stephens RS, Pelham WE, Skinner R. State-dependent and main effects of methylphenidate and pemoline on paired-associate learning and spelling in hyperactive children. J Consult Clin Psychol.1984;52 :104– 113
    OpenUrlCrossRefPubMed
  20. ↵
    Conners CK, Taylor E, Meo G, Kurtz MA, Fournier M. Magnesium pemoline and dextroamphetamine: a controlled study in children with minimal brain dysfunction. Psychopharmacologia.1972;26 :321– 336
  21. ↵
    Rapport MD, Carlson GA, Kelly KL, Pataki C. Methylphenidate and desipramine in hospitalized children: I. Separate and combined effects on cognitive function. J Am Acad Child Adolesc Psychiatry.1993;32 :333– 342
    OpenUrlPubMed
  22. ↵
    Quinn PO, Rapoport JL. One-year follow-up of hyperactive boys with imipramine and methylphenidate. Am J Psychiatry.1975;132 :241– 245
    OpenUrlPubMed
  23. ↵
    Werry JS, Aman MG, Diamond E. Imipramine and methylphenidate in hyperactive children. J Child Psychol Psychiatry.1980;21 :27– 35
    OpenUrlCrossRefPubMed
  24. ↵
    Fitzpatrick PA, Klorman R, Brumaghim JT, Borgstedt AD. Effects of sustained-release and standard preparations of methylphenidate on attention deficit disorder. J Am Acad Child Adolesc Psychiatry.1992;31 :226– 234
    OpenUrlPubMed
  25. Pelham WE Jr, Sturges J, Hoza J, et al. Sustained release and standard methylphenidate effects on cognitive and social behavior in children with attention deficit disorder. Pediatrics.1987;80 :491– 501
    OpenUrlAbstract/FREE Full Text
  26. ↵
    Whitehouse D, Shah U, Palmer FB. Comparison of sustained-release and standard methylphenidate in the treatment of minimal brain dysfunction. J Clin Psychiatry.1980;41 :282– 285
    OpenUrlPubMed
  27. ↵
    Srinivas NR, Hubbard JW, Quinn D, Midha KK. Enantioselective pharmacokinetics and pharmacodynamics of dl-threo-methylphenidate in children with attention deficit hyperactivity disorder. Clin Pharmacol Ther.1992;52 :561– 568
    OpenUrlCrossRefPubMed
  28. ↵
    Biederman J, Baldessarini RJ, Wright V, Knee D, Harmatz JS, Goldblatt A. A double-blind placebo controlled study of desipramine in the treatment of ADD: II. Serum drug levels and cardiovascular findings. J Am Acad Child Adolesc Psychiatry.1989;28 :903– 911
    OpenUrlPubMed
  29. Biederman J, Baldessarini RJ, Wright V, Knee D, Harmatz JS. A double-blind placebo-controlled study of desipramine in the treatment of ADD: I. Efficacy. J Am Acad Child Adolesc Psychiatry.1989;29 :777– 784
    OpenUrl
  30. Biederman J, Baldessarini RJ, Wright V, Keenan K, Farone S. A double-blind placebo controlled study of desipramine in the treatment of ADD: III. Lack of impact of comorbidity and family history factors on clinical response. J Am Acad Child Adolesc Psychiatry.1993;32 :199– 204
    OpenUrlPubMed
  31. Donnelly M, Zametkin AJ, Rapoport JL, et al. Treatment of childhood hyperactivity with desipramine: plasma drug concentration, cardiovascular effects, plasma and urinary catecholamine levels, and clinical response. Clin Pharmacol Ther.1986;39 :72– 81
    OpenUrlPubMed
  32. Gualtieri CT, Keenan PA, Chandler M. Clinical and neuropsychological effects of desipramine in children with attention deficit hyperactivity disorder. J Clin Psychopharmacol.1991;11 :155– 159
    OpenUrlPubMed
  33. Singer HS, Brown J, Quaskey S, Rosenberg LA, Mellits ED, Denckla MB. The treatment of attention-deficit hyperactivity disorder in Tourette's syndrome: a double-blind placebo-controlled study with clonidine and desipramine. Pediatrics.1995;95 :74– 81
    OpenUrlAbstract/FREE Full Text
  34. ↵
    Wilens TE, Biederman J, Prince J, et al. Six-week, double-blind, placebo-controlled study of desipramine for adult attention deficit hyperactivity disorder. Am J Psychiatry.1996;153 :1147– 1153
    OpenUrlPubMed
  35. ↵
    Gualtieri CT, Evans RW. Motor performance in hyperactive children treated with imipramine. Percept Mot Skills.1988;66 :763– 769
    OpenUrlPubMed
  36. ↵
    Winsberg BG, Kupietz SS, Yepes LE, Goldstein S. Ineffectiveness of imipramine in children who fail to respond to methylphenidate. J Autism Dev Disord.1980;10 :129– 137
    OpenUrlCrossRefPubMed
  37. ↵
    Brown RT, Wynne ME, Medenis R. Methylphenidate and cognitive therapy: a comparison of treatment approaches with hyperactive boys. J Abnorm Child Psychol.1985;13 :69– 87
    OpenUrlCrossRefPubMed
  38. Conrad WG, Dworkin ES, Shai A, Tobiessen JE. Effects of amphetamine therapy and prescriptive tutoring on the behavior and achievement of lower class hyperactive children. J Learn Disabil.1971;4 :509– 517
  39. ↵
    Firestone P, Crowe D, Goodman JT, McGrath P. Vicissitudes of follow-up studies: differential effects of parent training and stimulant medications with hyperactives. Am J Orthopsychiatry.1986;56 :184– 194
    OpenUrlPubMed
  40. ↵
    Klein RG, Abikoff H, Klass E, Ganeles D, Seese LM, Pollack S. Clinical efficacy of methylphenidate in conduct disorder with and without attention deficit hyperactivity disorder. Arch Gen Psychiatry.1997;54 :1073– 1080
    OpenUrlCrossRefPubMed
  41. ↵
    Arnold LE, Kleykamp D, Votolato NA, Taylor WA, Kontras SB, Tobin K. Gamma-linolenic acid for attention-deficit hyperactivity disorder: placebo-controlled comparison to D-amphetamine. Biol Psychiatry.1989;25 :222– 228
    OpenUrlCrossRefPubMed
  42. ↵
    Garfinkel BD, Webster CD, Sloman L. Responses to methylphenidate and varied doses of caffeine in children with attention deficit disorder. Can J Psychiatry.1981;26 :395– 401
    OpenUrlPubMed
  43. ↵
    Schechter MD, Timmons GD. Objectively measured hyperactivity–II. Caffeine and amphetamine effects. J Clin Pharmacol.1985;25 :276– 280
    OpenUrlCrossRefPubMed
  44. ↵
    Borden KA, Brown RT. Attributional outcomes: the subtle message of treatments for attention deficit disorder. Cognit Ther Res.1989;13 :147– 160
  45. ↵
    Brown RT, Borden KA, Wynne ME, Schleser R, Clingerman SR. Methylphenidate and cognitive therapy with ADD children: a methodological reconsideration. J Abnorm Child Psychol.1986;14 :481– 497
    OpenUrlCrossRefPubMed
  46. ↵
    Brown RT, Borden KA, Wynne ME, Spunt AL, Clingerman SR. Patterns of compliance in treatment program for children with attention deficit disorder. J Compliance Health Care.1988;3 :23– 29
  47. ↵
    Carlson CL, Pelham WE Jr, Milich R, Dixon J. Single and combined effects of methylphenidate and behavior therapy on the classroom performance of children with attention-deficit hyperactivity disorder. J Abnorm Child Psychol.1992;20 :213– 232
    OpenUrlCrossRefPubMed
  48. Christensen DE. Effects of combining methylphenidate and a classroom token system in modifying hyperactive behavior. Am J Ment Defic.1975;80 :266– 276
    OpenUrlPubMed
  49. Hinshaw SP, Henker B, Whalen CK. Cognitive-behavioral and pharmacologic interventions for hyperactive boys: comparative and combined effects. J Consult Clin Psychol.1984;52 :739– 749
    OpenUrlCrossRefPubMed
  50. Hinshaw SP, Buhrmester D, Heller T. Anger control in response to verbal provocation: effects of stimulant medication for boys with ADHD. J Abnorm Child Psychol.1989;17 :393– 407
    OpenUrlCrossRefPubMed
  51. ↵
    Abikoff H, Gittelman R. Hyperactive children treated with stimulants. Is cognitive training a useful adjunct? Arch Gen Psychiatry.1985;42 :953– 961
    OpenUrl
  52. Long N, Rickert VI, Ashcraft EW. Bibliotherapy as an adjunct to stimulant medication in the treatment of attention-deficit hyperactivity disorder. J Pediatr Health Care.1993;7 :82– 88
    OpenUrlCrossRefPubMed
  53. ↵
    Pelham WE Jr, Carlson C, Sams SE, Vallano G, Dixon MJ, Hoza B. Separate and combined effects of methylphenidate and behavior modification on boys with attention deficit-hyperactivity disorder in the classroom. J Consult Clin Psychol.1993;61 :506– 515
    OpenUrlCrossRefPubMed
  54. ↵
    Solanto MV, Wender EH, Bartell SS. Effects of methylphenidate and behavioral contingencies on sustained attention in attention-deficit hyperactivity disorder: a test of the reward dysfunction hypothesis. J Child Adolesc Psychopharmacol.1997;7 :123– 136
    OpenUrlPubMed
  55. ↵
    Fehlings DL, Roberts W, Humphries T, Dawe G. Attention deficit hyperactivity disorder: does cognitive behavioral therapy improve home behavior? J Dev Behav Pediatr.1991;12 :223– 228
    OpenUrlPubMed
  56. Gillberg C, Melander H, von Knorring AL, et al. Long-term stimulant treatment of children with attention-deficit hyperactivity disorder symptoms. A randomized, double-blind, placebo-controlled trial. Arch Gen Psychiatry.1997;54 :857– 864
    OpenUrlCrossRefPubMed
  57. Gittelman-Klein R, Klein DF, Abikoff H, Katz S, Gloisten AC, Kates W. Relative efficacy of methylphenidate and behavior modification in hyperkinetic children: an interim report. J Abnorm Child Psychol.1976;4 :361– 379
    OpenUrlCrossRefPubMed
  58. Greenhill LL, Rieder RO, Wender PH, Buchsbaum M, Zhan TP. Lithium carbonate in the treatment of hyperactive children. Arch Gen Psychiatry.1973;28 :636– 640
    OpenUrlCrossRefPubMed
  59. Linden M, Habib T, Radojevic V. A controlled study of the effects of EEG biofeedback on cognition and behavior of children with attention deficit disorder and learning disabilities. Biofeedback Self Regul.1996;21 :35– 49
    OpenUrlCrossRefPubMed
  60. ↵
    Schachar RJ, Tannock R, Cunningham C, Corkum PV. Behavioral, situational, and temporal effects of treatment of ADHD with methylphenidate. J Am Acad Child Adolesc Psychiatry.1997;36 :754– 763
    OpenUrlCrossRefPubMed
  61. ↵
    Bloomquist ML, August GJ, Ostrander R. Effects of school-based cognitive-behavioral intervention for ADHD children. J Abnorm Child Psychol.1991;19 :591– 605
    OpenUrlCrossRefPubMed
  62. ↵
    Firestone P, Kelly MJ, Goodman JT, Davey J. Differential effects of parent training and stimulant medication with hyperactives: a progress report. J Am Acad Child Psychiatry.1981;20 :135– 147
    OpenUrlPubMed
  63. ↵
    Goyette CH, Conners CK, Ulrich RF. Normative data on revised Conners Parent and Teacher Rating Scales. J Abnorm Child Psychol.1978;6 :221– 236
    OpenUrlCrossRefPubMed
  64. ↵
    Conners CK. Is ADHD a disease? J Atten Disord.1997;2 :3– 17
    OpenUrlCrossRef
  65. ↵
    Quay HC, Peterson DR. Manual for the Revised Behavioral Problem Checklist. Coral Gables, FL: University of Miami; 1987
  66. ↵
    Jensen PS, Kettle L, Roper MT, et al. Are stimulants overprescribed? Treatment of ADHD in four U.S. communities. J Am Acad Child Adolesc Psychiatry.1999;38 :797– 804
    OpenUrlCrossRef
  67. ↵
    Jensen PS, Hinshaw SP, Kraemer HC, et al. ADHD comorbidity findings from the MTA study: comparing comorbid subgroups. J Am Acad Child Adolesc Psychiatry.2001;40 :147– 158
    OpenUrlCrossRefPubMed
  68. ↵
    March JS, Swanson JM, Arnold LE, et al. Anxiety as a predictor and outcome variable in the multimodal treatment study of children with ADHD (MTA). J Abnorm Child Psychol.2000;28 :527– 541
    OpenUrlCrossRefPubMed
  69. ↵
    Conners CK, Epstein JN, March JS, et al. Multimodal treatment of ADHD in the MTA: an alternative outcome analysis. J Am Acad Child Adolesc Psychiatry.2001;40 :159– 167
    OpenUrlCrossRefPubMed
  70. ↵
    Wells KC, Epstein JN, Hinshaw SP, et al. Parenting and family stress treatment outcome in attention-deficit hyperactivity disorder (ADHD): an empirical analysis in the MTA study. J Abnorm Child Psychol.2000;28 :543– 553
    OpenUrlCrossRefPubMed
  71. ↵
    Hinshaw SP, Owens EB, Wells KC. Family process and treatment outcomes in the MTA: negative/ineffective parenting practices in relation to multimodal treatment. J Abnorm Child Psychol.2000;28 :555– 568
    OpenUrlCrossRefPubMed
  72. ↵
    Pelham WE, Gragy EM, Greiner AR, et al. Behavioral versus behavioral and pharmacological treatment in ADHD children attending a summer treatment program. J Abnorm Child Psychol.2000;28 :507– 525
    OpenUrlCrossRefPubMed
  73. ↵
    Klassen A, Raina P, Miller A, Lee S. Attention deficit hyperactivity disorder in children. Benefits of adding other forms of treatment to medication remain unclear [letter]. BMJ.1998;317 :1251
    OpenUrl
  74. ↵
    Pfiffner L, McBurnett K. Social skills training with parent generalization: treatment effects for children with attention deficit disorder. J Consult Clin Psychol.1997;65 :749– 757
    OpenUrlCrossRefPubMed
  75. ↵
    Horn WF, Ialongo NS, Pascoe JM, et al. Additive effects of psychostimulants, parent training, and self-control therapy with ADHD children. J Am Acad Child Adolesc Psychiatry.1991;30 :233– 240
    OpenUrlPubMed
  76. ↵
    Hall CW, Kataria S. Effects of two treatment techniques on delay and vigilance tasks with attention deficit hyperactive disorder (ADHD) children. J Psychol.1992;126 :17– 25
    OpenUrlPubMed
  77. ↵
    Kolko DJ, Burstein OG, Barron J. Methylphenidate and behavior modification in children with ADHD and comorbid ODD or CD: main and incremental effects across settings. J Am Acad Child Adolesc Psychiatry.1999;38 :578– 586
    OpenUrlCrossRefPubMed
  78. ↵
    Klein RG, Abikoff H. Behavior therapy and methylphenidate in the treatment of children with ADHD. J Atten Disord.1997;2 :89– 114
    OpenUrlAbstract
  79. ↵
    Ialongo NS, Horn WF, Pascoe JM, et al. The effects of a multimodal intervention with attention-deficit hyperactivity disorder children: a 9-month follow-up. J Am Acad Child Adolesc Psychiatry.1993;32 :182– 189
    OpenUrlPubMed
  80. ↵
    Kratochvil CJ, Vaughan BS, Harrington MJ, Burke WJ. Atomoxetine: a selective noradrenaline reuptake inhibitor for the treatment of attention-deficit/hyperactivity disorder. Expert Opin Pharmacother.2003;4 :1165– 1174
    OpenUrlCrossRefPubMed
  81. ↵
    Michelson D, Faries D, Wernicke J, et al. Atomoxetine in the treatment of children and adolescents with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled, dose-response study. Pediatrics.2001;108 (5). Available at: www.pediatrics.org/cgi/content/full/108/5/e83
  82. ↵
    Kratochvil CJ, Heiligenstein JH, Dittmann R, et al. Atomoxetine and methylphenidate treatment in children with ADHD: a prospective, randomized, open-label trial. J Am Acad Child Adolesc Psychiatry.2002;41 :776– 784
    OpenUrlCrossRefPubMed
  83. ↵
    Wernicke JF, Faries D, Girod D, et al. Cardiovascular effects of atomoxetine in children, adolescents, and adults. Drug Saf.2003;26 :729– 740
    OpenUrlCrossRefPubMed
  84. ↵
    Michelson D, Allen AJ, Busner J, et al. Once-daily atomoxetine treatment for children and adolescents with attention deficit hyperactivity disorder: a randomized, placebo-controlled study. Am J Psychiatry.2002;159 :1896– 1901
    OpenUrlCrossRefPubMed
  85. ↵
    Anderson EE, Clement PW, Oettinger L Jr. Methylphenidate compared with behavioral self-control in attention deficit disorder: preliminary report. J Dev Behav Pediatr.1981;2 :137– 141
    OpenUrlPubMed
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Treatment of Attention-Deficit/Hyperactivity Disorder: Overview of the Evidence
Ronald T. Brown, Robert W. Amler, Wendy S. Freeman, James M. Perrin, Martin T. Stein, Heidi M. Feldman, Karen Pierce, Mark L. Wolraich
Pediatrics Jun 2005, 115 (6) e749-e757; DOI: 10.1542/peds.2004-2560

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Treatment of Attention-Deficit/Hyperactivity Disorder: Overview of the Evidence
Ronald T. Brown, Robert W. Amler, Wendy S. Freeman, James M. Perrin, Martin T. Stein, Heidi M. Feldman, Karen Pierce, Mark L. Wolraich
Pediatrics Jun 2005, 115 (6) e749-e757; DOI: 10.1542/peds.2004-2560
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  • Article
    • Abstract
    • INTRODUCTION
    • McMASTER UNIVERSITY EVIDENCE-BASED PRACTICE CENTER REVIEW
    • MULTIMODAL TREATMENT STUDY OF CHILDREN WITH ADHD
    • ADDITIONAL SUBCOMMITTEE SEARCH AND REVIEW
    • CONCLUSIONS
    • ADDENDUM
    • Committee on Quality Improvement, 1999–2000
    • Liaisons
    • Subcommittee on Attention-Deficit/Hyperactivity Disorder
    • Consultants
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