The Efficacy of Atomoxetine for the Treatment of Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: A Comprehensive Review of Over a Decade of Clinical Research

Atomoxetine was first licensed to treat attention-deficit/hyperactivity disorder (ADHD) in children and adolescents in the US in 2002. The aim of this paper is to comprehensively review subsequent publications addressing the efficacy of atomoxetine in 6- to 18-year-olds with ADHD. We identified 125 eligible papers using a predefined search strategy. Overall, these papers demonstrate that atomoxetine is an effective treatment for the core ADHD symptoms (effect sizes 0.6–1.3, vs. placebo, at 6–18 weeks), and improves functional outcomes and quality of life, in various pediatric populations with ADHD (i.e., males/females, patients with co-morbidities, children/adolescents, and with/without prior exposure to other ADHD medications). Initial responses to atomoxetine may be apparent within 1 week of treatment, but can take longer (median 23 days in a 6-week study; n = 72). Responses often build gradually over time, and may not be robust until after 3 months. A pooled analysis of six randomized placebo-controlled trials (n = 618) indicated that responses at 4 weeks may predict response at 6–9 weeks, although another pooled analysis of open-label data (n = 338) suggests that the probability of a robust response to atomoxetine [≥40 % decrease in ADHD–Rating Scale (ADHD-RS) scores] may continue to increase beyond 6–9 weeks. Atomoxetine may demonstrate similar efficacy to methylphenidate, particularly immediate-release methylphenidate, although randomized controlled trials are generally limited by short durations (3–12 weeks). In conclusion, notwithstanding these positive findings, before initiating treatment with atomoxetine, it is important that the clinician sets appropriate expectations for the patient and their family with regard to the likelihood of a gradual response, which often builds over time.