OBJECTIVE: Medications used to treat attention-deficit/hyperactivity disorder (ADHD) have been well researched, but comparisons among drugs are hindered by the absence of direct comparative trials. METHODS: We analyzed recent published literature on the pharmacotherapy of ADHD to describe the variability of drug-placebo effect sizes. A literature search was conducted to identify double-blind, placebo-controlled studies of ADHD youth published after 1979. Meta-analysis regression assessed the influence of medication type and study design features on medication effects. RESULTS: Twenty-nine trials met criteria and were included in this meta-analysis. These trials studied 15 drugs using 17 different outcome measures of hyperactive, inattentive, impulsive, or oppositional behavior. The most commonly identified treatments included both methylphenidate and amphetamine compounds. After stratifying trials on the class of drug studied (short-acting stimulant vs long-acting stimulant vs nonstimulant), we found significant drug differences for both study design variables and effect sizes. The differences among the 3 classes of drug remained significant after correcting for study design variables. Conclusion: Uniformity appears to be lacking in how medication effectiveness is assessed and in many study design parameters. Comparing medication effect sizes from different studies will be biased without accounting for variability in study design parameters. Although these differences obscure comparisons among specific medications, they do allow for conclusions about the differential effects of broad classes of medications used to treat ADHD.
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