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Eur Child Adolesc Psychiatry (2010) 19:353364 DOI 10.1007/s00787-009-0054-3
ORIGINAL CONTRIBUTION
Comparing the efcacy of stimulants for ADHD in children and adolescents using meta-analysis
Stephen V. Faraone Jan Buitelaar
Received: 14 January 2009 / Accepted: 20 August 2009 / Published online: 10 September 2009 Springer-Verlag 2009
Abstract Stimulants used to treat attention-decit/ hyperactivity disorder (ADHD) have been well researched, but comparisons among stimulants are hindered by the absence of direct comparative trials. The goal of this work was to compare the efcacy of methylphenidate and amfetamine formulations through a meta-analysis of double-blind placebo-controlled trials. We analyzed recent published literature on the stimulant therapy of ADHD to describe the variability of drugplacebo effect sizes. A literature search was conducted to identify double-blind, placebo-controlled studies of ADHD in children and adolescents published after 1979. Meta-analysis regression assessed the inuence of medication type and study design features on medication effects. Twenty-three trials met criteria and were included in this meta-analysis. These trials studied 11 drugs using 19 different outcome measures of hyperactive, inattentive, or impulsive behavior. We found signicant differences between amfetamine and methylphenidate products, even after correcting for study design features that might have confounded the results. Our analyses indicate that effect sizes for amfetamine products are signicantly, albeit moderately, greater than those for methylphenidate. We found that most measures of effect
from all studies were statistically signicant. Our ndings suggest that amfetamine products may be moderately more efcacious than methylphenidate products, even after controlling for potentially confounding study design features. This difference in effect size may be due to differences between amfetamine and methylphenidate in the molecular mechanisms involved in facilitating the dopaminergic neurotransmission.
Keywords ADHD Medications Efcacy Effect size
Meta-analysis
Introduction
Attention-decit/hyperactivity disorder (ADHD) is a neurocognitive disorder with a high worldwide prevalence [22]. For decades, the stimulant medications methylphenidate, dexamfetamine, and mixed amfetamine salts have been the most common drugs used in the treatment of ADHD. The stimulants as a class increase the availability of synaptic dopamine [45, 46], but the mechanism involved differs between methylphenidate and amfetamines. Methylpheni-date can be viewed as a dopamine reuptake inhibitor, which facilitates dopaminergic neurotransmission at the dopamine transporter, and elicits little presynaptic dopamine release [35]. In contrast, amfetamines are thought to block the reuptake of both norepinephrine and...