Efficacy and safety of atomoxetine for attention-deficit/hyperactivity disorder in children and adolescents-meta-analysis and meta-regression analysis

Objectives The objective of this study was to evaluate the efficacy and safety of atomoxetine in children and adolescents. Materials and methods We searched for studies published between 1985 and 2006 through Medline, PubMed, PsychInfo and Cochrane Central Register of Controlled Trials (CENTRAL 2006 Issue 3) using keywords related to atomoxetine and attention-deficit/hyperactivity disorder (ADHD) and scanned though reference lists. We included nine randomized placebo-controlled trials (atomoxetine:placebo=1,150:678). Results Atomoxetine was superior (p < 0.01) to placebo in reducing ADHD symptoms across different scales (Attention-Deficit/Hyperactivity Disorder Rating Scale-IV, Conners' Parent and Teacher Rating Scales-Revised:Short Form, Clinical Global Impression-Severity) rated by different raters (parent, teacher, clinician). The number-needed-to-treat (NNTs) for treatment response and relapse prevention were 3.43 (95% CI, 2.79-4.45) and 10.30 (95% CI, 5.89-40.62), respectively. High baseline ADHD symptoms (p=0.02) was associated with greater reduction in ADHD symptoms, whereas male gender (p=0.02), comorbid oppositional defiant disorder (ODD) status (p=0.01) and ADHD hyperactive/impulsive subtype (p=0.01) were associated with smaller reductions. The commonest adverse events were gastrointestinal [appetite decrease, number-needed-to-harm (NNH)=8.81; abdominal pain, NNH=22.48; vomiting, NNH=29.96; dyspepsia, NNH=49.38] and sleep related (somnolence, NNH=19.41). Young age (p=0.03) and high baseline hyperactive/impulsive symptoms (p < 0.01) were associated with more adverse events, whereas ADHD inattentive subtype (p=0.04) was associated with less adverse events. Quality of life using Child Health Questionnaire (CHQ) improved (p < 0.01) with atomoxetine treatment. Both ADHD and ODD symptoms (p < 0.01) were reduced in comorbid ADHD+ODD, and ODD status was not associated with more adverse events. Efficacy and side effects were not altered by comorbid general anxiety disorder or major depression. Conclusions Atomoxetine is efficacious in reducing ADHD symptoms. It may have a role in treating comorbid ODD or depression, and probably in comorbid anxiety.