Atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder: a 6-week, randomized, placebo-controlled, double-blind trial in Russia

Abstract

The objective of the study was to compare the efficacy and tolerability of once-daily atomoxetine (< or =1.8 mg/(kg day) with those of placebo in children and adolescents (aged 6-16 years) with attention-deficit/hyperactivity disorder [ADHD (DSM-IV)]. This randomized, placebo-controlled, double-blind trial was conducted in Russia. The primary efficacy measure was baseline-to-end point changes in Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored (ADHDRS-IV-Parent:Inv) total score. Tolerability measures included treatment-emergent signs and symptoms (TESS), laboratory values and weight. Compared with patients in the placebo group (n = 33), patients treated with atomoxetine (n = 72) with a mean final dose of 1.4 mg/kg showed significantly greater improvement in ADHDRS-IV-Parent:Inv total score (least-squares mean: atomoxetine, -15.8; placebo, -11.4; p = 0.013). The most common TESS in the atomoxetine group included anorexia [atomoxetine, n = 13 (18.1%); placebo, n = 2 (6.1%)], somnolence, n = 11 versus n = 3 (15.3% vs. 9.1%, respectively), abdominal pain n = 9 versus n = 1 (12.5% vs. 3.0%, respectively) and nausea, n = 8 versus n = 1 (11.1% vs. 3.0%, respectively). Seven patients in the atomoxetine group and two in the placebo group experienced clinically important weight loss during the study (> or =7% from baseline; mean change, kg: atomoxetine, -0.6; placebo, 0.1; p = 0.032). Atomoxetine is efficacious in improving ADHD symptoms in children and adolescents. Atomoxetine treatment may be associated with a numerically higher incidence of anorexia, somnolence, abdominal pain and nausea, as well as statistically greater losses in body weight.

Systematic review of atomoxetine data in childhood and adolescent attention-deficit hyperactivity disorder 2009–2011: Focus on clinical efficacy and safety

“…Similar results were seen using change in ADHD-RS in the 10-week study, giving a final effect size of 1.3, with 63% of patients having a response of >40% (Svanborg et al, 2009), although this study was not powered to measure the effect size using ADHD-RS. In the 6-week study there appeared to be a linear reduction with no suggestion of plateau at 6 weeks (Martényi et al, 2010). In a further placebo RCT 6-week study (not in treatment-naïve patients) comparing morning and evening dosing, measuring change in the ADHD-RS total score, both cohorts showed continuing improvements until week 6 with no evident plateau, with an effect size in the morning dosing group of 0.7; evening dosing was not significantly different to placebo on this measure (Block et al, 2009).…”

“…A critical finding in the treatment-naïve studies (Martényi et al, 2010;Montoya et al, 2009;Svanborg et al, 2009) was that effect size of ATX was greatest at study completion (6, 10, and 12 weeks, respectively), and in the Montoya study showed no sign of plateau even at 12 weeks (Montoya et al, 2009). The effect size at 6 weeks of 0.55 had increased in almost linear manner to 0.82 at 12 weeks (Montoya et al, 2009).…”

“…Onset of response is reported in five placebo studies predominantly measured by the Attention-deficit Hyperactivity Disorder Rating Scale (Table 1). In a 6-week RCT of treatment-naïve patients, the ATX cohort was significantly improved at 4 weeks (p=0.042) (at 2 weeks p=0.054) (Martényi et al, 2010) and treatment-naïve studies of longer durations (10 and 12 weeks) reported onset of response at Week 3 (p<0.001) and Week 4 (p=0.003), respectively (Montoya et al, 2009;Svanborg et al, 2009). In non-treatment-naïve trials a 6-week study comparing morning and evening dosing with placebo reported significant improvement in ADHD-RS at 1 week in both dosing arms (Block et al, 2009), and an 8-week study reported improvement at week 2 but only in the 1.8 mg/kg cohort (Takahashi et al, 2009 In a post hoc analysis of two open-label studies (n=421) over 24 weeks using the Weekly Rating of Evening and Morning Behaviour (WREMB-R) and Global Impression of Perceived Difficulties (GIPD) scales, significant improvement was measured predominantly over the initial 2 weeks with maintenance over 24 weeks .…”

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

“…We found seven studies that reported the proportions of patients who experienced particular percentage reductions in weight [18,21,69,74,78,82,87]. For example, in a short-term (6-week) RCT with a patient population aged 6-16 years, ''clinically important weight loss'' (C7 % from baseline) was observed in 9.7 % of 72 atomoxetine-treated patients versus 6.1 % of 33 placebo-treated patients [82].…”

“…Weight In short-term controlled and open-label studies (B18 weeks), reductions in weight have been reported in children and adolescents during treatment with atomoxetine [18,53,55,62,65,67,74,79,82,89]. However, reductions in body weight are not universally reported: the authors of some short-term studies (B14 weeks) report either no change or a small increase in mean weight [55,69,75,80,81] and/or describe weight changes as not ''clinically significant'', not ''clinically meaningful'', or ''small'' [55,67,79,80,86].…”