Effect of comorbid symptoms of oppositional defiant disorder on responses to atomoxetine in children with ADHD: a meta-analysis of controlled clinical trial data

Rationale Up to 60% of children with attention-deficit/hyperactivity disorder (ADHD) suffer from comorbid affective or behavioral impairments, the most common condition being oppositional defiant disorder (ODD), which occurs in 40-60% of children with ADHD. Objectives This post hoc meta-analysis was performed to determine the effect of the presence of comorbid ODD symptoms on clinical outcomes among pediatric and adolescent subjects being treated for ADHD. Methods Acute-phase data were analyzed from three randomized, double-blind, placebo-controlled studies in outpatients aged 6-16 and meeting the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, criteria for ADHD. Subjects received placebo or atomoxetine (max 1.8 mg/kg/day, daily) for 6-8 weeks. Patients were diagnosed with comorbid ODD on structured diagnostic interview (Schedule for Affective Disorders and Schizophrenia for School-aged Children-Present and Lifetime Versions). Results Of the 512 subjects studied, 158 were diagnosed with comorbid ODD. Relative to placebo, atomoxetine treatment significantly reduced ADHD symptoms in both ODD-comorbid and noncomorbid subjects irrespective of the comorbidity with ODD. ADHD subjects also showed significant improvements from baseline on most of the psychosocial measures of the child health questionnaire irrespective of the comorbidity with ODD. Reduction in ODD symptoms was highly related to the magnitude of ADHD response. Conclusions Atomoxetine treatment significantly reduced ADHD symptoms in both ODD-comorbid and noncomorbid subjects to similar extents, indicating that the presence of comorbid symptoms of oppositionality does not affect clinical outcomes of treatment of ADHD with atomoxetine.