Understanding the Effect Size of ADHD Medications

Introduction

For decades, the stimulant medications methylphenidate, dextroamphetamine, and mixed amphetamine salts have been the mainline pharmacotherapy of attention-deficit/hyperactivity disorder (ADHD), a disorder that, due to its high prevalence around the world,^[1] is a serious public health problem. Studies demonstrate robust effects in both children and adults,^[2] and meta-analyses of the most frequently studied stimulant, methylphenidate, show consistent efficacy across studies in children, adolescents, and adults.

Although stimulants had been the mainstay of ADHD pharmacotherapy for many years, physicians are now faced with many choices when they plan the pharmacotherapy of ADHD youth. The range of medicines presented as having efficacy for ADHD now include several nonstimulants. These include tricyclic antidepressants (imipramine, desipramine, amitriptyline, nortriptyline, and clomipramine), bupropion, modafinil, monoamine oxidase inhibitors, and the selective norepinephrine transporter inhibitor atomoxetine. In addition to these nonstimulant medicines, recent formulations of immediate-release stimulant medicines extend their duration of action to allow once-a-day dosing to cover 8 to 12 hours of the day.

How should physicians choose among the many medications presented to them as being efficacious for treating ADHD symptoms? The practice of evidence-based medicine provides an answer. Advocates of this approach to treatment selection urge physicians to base treatment choices on the best evidence from systematic research about the efficacy and adverse effects of treatment alternatives. Ideally, physicians could compare different medications by referring to randomized, double-blind, placebo-controlled studies that compared the medications. Although the medicines that treat ADHD have been well researched, studies comparing medications are rare. In the absence of direct comparative trials, the best evidence comes from comparing randomized, double-blind, placebo-controlled studies of each medication. This column reviews methods for comparing drugs across studies and provides examples of how they can be applied to the medicines that treat ADHD.