Methylphenidate and Desipramine in Hospitalized Children with Comorbid Behavior and Mood Disorders: Separate and Combined Effects on Behavior and Mood

Desipramine (DMI), methylphenidate (MPH), and combined DMI+MPH were examined to assess their differential efficacy in treating problems of inattention, hyperactivity, oppositional/aggressive symptoms, self-control, and mood in children with comorbid mood and behavior disorders. A double-blind placebo-controlled crossover experimental study was conducted on 16 psychiatrically hospitalized children (ages 7–12) with diagnoses of attention-deficit hyperactivity disorder, a nonbipolar mood disorder (major depressive disorder or dysthymic disorder), or both. In addition, all children had either conduct disorder or oppositional defiant disorder. Behavior and mood were rated in school weekly, and on the inpatient unit (days and evenings separately). Each of the 16 subjects was observed and interviewed on methylphenidate 20 mg daily, desipramine (adjusted to therapeutic levels), and a combination of these two treatments, and the findings were compared to baseline and placebo. Statistically significant improvements were observed for the combination of DMI and MPH, in comparison to placebo, beyond those seen with either drug alone. However, the clinical improvements with DMI+MPH were modest. There was no evidence that stimulant medication and DMI potentiated each other's effects in treating symptoms of major depressive disorder or dysthymic disorder. Compared to placebo, the combined DMI+MPH treatment was most effective at improving self-control and reducing inattention, hyperactivity, and aggressive behavior. Further, there was no differential efficacy of DMI and MPH for treating symptoms of depressive disorders. Overall, this study, the first controlled trial of combined DMI+MPH in children, demonstrated statistically significant but clinically modest effects in these complex children presenting with comorbid nonbipolar mood disorder, ADHD, and an additional behavior disorder. Cognitive changes and adverse effects have been previously reported.