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01-02-2015 | Review Article

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

Authors: Nicola C. Savill, Jan K. Buitelaar, Ernie Anand, Kathleen Ann Day, Tamás Treuer, Himanshu P. Upadhyaya, David Coghill

Published in: CNS Drugs | Issue 2/2015

Abstract

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.

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Response was defined as “at least a 25 % decrease from baseline on the ADHD-RS-IV [ADHD–Rating Scale–IV] total score”.

Remission was defined as “each ADHD-RS-IV item score ≤1 at the end of the treatment”.

However, these results should be viewed with caution, particularly as the congress abstract does not state a definition for “treatment failure”, and we are not aware of these results having been published in a full-length peer-reviewed study paper or of being replicated.

The primary outcome measure was comparison of mean time to relapse, defined as an increase in ADHD-RS total score to 90 % of the score at study entry and an increase in CGI–Severity [CGI-S] score of ≥2 points above the CGI-S score at the end of the initial 10 weeks of treatment. A secondary definition of relapse (≥50 % worsening in ADHD-RS severity score above the last pre-randomization visit) resulted in similar relapse rates [atomoxetine, 6/81 (7.4 %); placebo, 16/82 (19.5 %); p = 0.037; relative risk ratio, 3.0 (95 % CI 1.2–7.6)]. A greater number of patients who received atomoxetine completed the 6-month randomized phase [65/79 (82.3 %)] than did those who received placebo [54/81 (66.7 %); p = 0.030].

The definition of non-inferiority was “if the lower limit of the 2-sided 95 % CI for the difference in proportion of responders (ATX [atomoxetine] minus MPH [methylphenidate]) is greater than −15%, ATX will be considered non-inferior to MPH”.

In the meta-analysis paper [143], and the source study in this paper, it is unclear whether ‘deprenyl’ referred to L-deprenyl (also known as selegiline), D-deprenyl, or a racemic mixture.

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Title: 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
Authors: Nicola C. Savill
Jan K. Buitelaar
Ernie Anand
Kathleen Ann Day
Tamás Treuer
Himanshu P. Upadhyaya
David Coghill
Publication date: 01-02-2015
Publisher: Springer International Publishing
Published in: CNS Drugs / Issue 2/2015
Print ISSN: 1172-7047
Electronic ISSN: 1179-1934
DOI: https://doi.org/10.1007/s40263-014-0224-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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