A comparison of the efficacy of medications for adult attention-deficit/hyperactivity disorder using meta-analysis of effect sizes

J Clin Psychiatry. 2010 Jun;71(6):754-63. doi: 10.4088/JCP.08m04902pur. Epub 2009 Dec 29.


Objectives: Medications used to treat attention-deficit/hyperactivity disorder (ADHD) in adults have been well researched, but comparisons among drugs are hindered by the absence of direct comparative trials. Our objectives were to (1) estimate the effect size of the medications used to treat adult ADHD, (2) determine if differences in the designs of studies confound comparisons of medication efficacy, (3) quantify the evidence for differences in effect sizes among medications, and (4) see if features of study design influence estimates of efficacy.

Data sources: The following search engines were used: PubMed, Ovid, ERIC, CINAHL, MEDLINE, PREMEDLINE, the Cochrane database, e-psyche, and Social Sciences Abstracts. Presentations from the American Psychiatric Association and American Academy of Child and Adolescent Psychiatry meetings were reviewed.

Study selection: A literature search was conducted to identify double-blind, placebo-controlled studies of ADHD in adults published in English after 1979. Only trials that used DSM-III, -III-R, or -IV ADHD criteria and followed subjects for > or = 2 weeks were selected.

Data extraction: Meta-analysis regression assessed the influence of medication type and study design features on medication effects.

Results: Nineteen trials met criteria and were included in this meta-analysis. These trials studied 13 drugs using 18 different outcome measures of hyperactive, inattentive, or impulsive behavior. After trials were stratified on the class of drug studied (short-acting stimulant vs long-acting stimulant vs nonstimulant), significant differences in effect size were observed between stimulant and nonstimulant medications (P = .006 and P = .0001, respectively, for short- and long-acting stimulants vs nonstimulants), but the effect for short-acting stimulants was not significant after correcting for study design features. The effect sizes for each drug class were similar in magnitude to what we previously reported for medication treatment studies of children with ADHD. We found significant heterogeneity of effect sizes for short-acting stimulants (P < .001) but not for other medication groups.

Conclusions: Although both stimulant and nonstimulant medications are effective for treating ADHD in adults, stimulant medications show greater efficacy for the short durations of treatment characteristic of placebo-controlled studies. We found no significant differences between short- and long-acting stimulant medications. Study design features vary widely among studies and can confound indirect comparisons unless addressed statistically as we have done in this study.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenergic Uptake Inhibitors / therapeutic use
  • Adult
  • Age Factors
  • Atomoxetine Hydrochloride
  • Attention Deficit Disorder with Hyperactivity / diagnosis
  • Attention Deficit Disorder with Hyperactivity / drug therapy*
  • Bupropion / therapeutic use
  • Central Nervous System Stimulants / therapeutic use*
  • Diagnostic and Statistical Manual of Mental Disorders
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Medication Adherence
  • Placebos
  • Propylamines / therapeutic use
  • Psychiatric Status Rating Scales
  • Randomized Controlled Trials as Topic / statistics & numerical data
  • Regression Analysis
  • Research Design / statistics & numerical data
  • Search Engine
  • Treatment Outcome


  • Adrenergic Uptake Inhibitors
  • Central Nervous System Stimulants
  • Placebos
  • Propylamines
  • Bupropion
  • Atomoxetine Hydrochloride