Once-Daily Treatment With Atomoxetine in Adults With Attention-Deficit/Hyperactivity Disorder: A 24-Week, Randomized, Double-Blind, Placebo-Controlled Trial

Objectives: Atomoxetine (ATX) once daily was compared with placebo (PBO) in adults with attention-deficit/hyperactivity disorder (ADHD) at 12 and 24 weeks. Methods: Patients were randomized to PBO (n = 234) or ATX (60-100 mg; n = 268) for 24 weeks following a 2-week on-label (40 mg for 3 days then 80 mg) or slow (40 mg for 7 days then 80 mg) titration. After 24 weeks, PBO patients were rerandomized to either ATX titration strategy. Efficacy measures included the Conners' Adult ADHD Rating Scale Total ADHD Symptoms score, Clinical Global Impression-ADHD-Severity, Montgomery-Asberg Depression Rating Scale, and State-Trait Anxiety Inventory. General and titration safety measures and tolerability were evaluated. Results: Conners' Adult ADHD Rating Scale Total ADHD Symptoms score reduction was greater with ATX over PBO at 12 weeks (-14.33 vs -10.05; P < 0.001) and 24 weeks (-16.43 vs -8.65; P < 0.001; effect size, 0.57). Response (25% decrease on Conners' Adult ADHD Rating Scale Total ADHD Symptoms) was greater for ATX (68%) than PBO (42%; P < 0.001) at 24 weeks. Clinical Global Impression-ADHD-Severity improvement was greater for ATX over PBO at 8 and 24 weeks (P < 0.001; effect sizes, 0.45 and 0.46, respectively). There were no significant changes in depressive or anxiety measures for either group. Discontinuation due to an adverse event was greater for on-label versus slow titration, although the rate of patients experiencing adverse events were comparable. Common adverse events included dry mouth, nausea, and decreased appetite. Conclusions: Atomoxetine demonstrated significant improvement in ADHD symptoms at 12 and 24 weeks over PBO. Adverse events overall and for on-label or slow titration to ATX were similar and consistent with previous adult ATX studies.