Atomoxetine for the treatment of attention-deficit/hyperactivity disorder and oppositional defiant disorder.

OBJECTIVE

In this study we examined the effectiveness of atomoxetine for the treatment of oppositional defiant disorder comorbid with attention-deficit/hyperactivity disorder.

METHODS

Patients were aged 6 to 12 years and met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnostic criteria for attention-deficit/hyperactivity disorder with a Swanson, Nolan, and Pelham Rating Scale-Revised attention-deficit/hyperactivity disorder subscale score above age and gender norms; Clinical Global Impressions-Severity Scale score of > or = 4; and Swanson, Nolan, and Pelham Rating Scale-Revised oppositional defiant disorder subscale score of > or = 15. Patients were randomly assigned in a 2:1 ratio to receive 1.2 mg/kg per day of atomoxetine (n = 156) or placebo (n = 70) for 8 weeks. Treatment effect on oppositional defiant disorder and attention-deficit/hyperactivity disorder symptoms was measured by using the investigator-rated Swanson, Nolan, and Pelham Rating Scale-Revised.

RESULTS

Repeated-measures analysis demonstrated a statistically significant difference favoring atomoxetine over placebo in the reduction of Swanson, Nolan, and Pelham Rating Scale-Revised oppositional defiant disorder total scores. There were significant pairwise treatment differences at weeks 2 and 5 but not at week 8 postbaseline. A last-observation-carried-forward analysis showed Swanson, Nolan, and Pelham Rating Scale-Revised scores at endpoint for the atomoxetine and placebo groups were significantly different for attention-deficit/hyperactivity disorder symptoms but not for oppositional defiant disorder symptoms. Atomoxetine was superior to placebo in a last-observation-carried-forward analysis of Clinical Global Impression-Improvement and Clinical Global Impression-Severity scores.

CONCLUSIONS

This study confirms previous findings that patients with attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder show statistically and clinically significant improvement in attention-deficit/hyperactivity disorder symptoms and global clinical functioning when treated with atomoxetine. It remains uncertain, however, whether atomoxetine exerts a specific and enduring effect on oppositional defiant disorder symptoms.