The efficacy and tolerability of quetiapine versus divalproex for the treatment of impulsivity and reactive aggression in adolescents with co-occurring bipolar disorder and disruptive behavior disorder(s)

Abstract

Objective: The aim of this study was to compare the efficacy and tolerability of quetiapine and divalproex for the treatment of impulsivity and reactive aggression in adolescents with co-occurring bipolar disorder and disruptive behavior disorders.

Method: Patients were included in this post hoc analysis if they scored > or = 14 on the Positive and Negative Syndrome Scale (PANSS) Excited Component (EC) and > or = 4 on at least one of the PANSS EC items, had a current diagnosis of bipolar I disorder, manic or mixed episode, and had a lifetime and/or current diagnosis of a disruptive behavioral disorder (DBD) [conduct disorder (CD) or oppositional defiant disorder (ODD)]. Thirty-three (92%) of the 36 subjects with bipolar disorder and DBD met the PANSS EC inclusion criteria. These thirty-three adolescents were randomized to quetiapine (400-600 mg/day) or divalproex (serum level 80-120 microg/mL) for 28 days in this double-blinded study. The primary efficacy measure was change in PANSS Excited Component (EC) score over the study period and at each time point.

Results: Repeated measures analysis of variance (ANOVA) demonstrated statistically significant within-treatment-group effects for divalproex (baseline = 20.6, end point = 13.3, p < 0.0001) and quetiapine (baseline = 18.8, end point = 10.8, p < 0.0001) for the PANSS EC. There were no statistically significant treatment group differences in PANSS EC changes from baseline to end point scores (p = 0.7, d = 0.14). Mixed regression analyses (comparison of slopes, DAY*TREATMENT) revealed that there was no significant difference in the rate of improvement in the PANSS EC scores between the two treatment groups [F(1,31) = 0.78, p = 0.39, d = 0.28].

Conclusions: Quetiapine and divalproex showed similar efficacy for the treatment of impulsivity and reactive aggression related to co-occurring bipolar and disruptive behavior disorders in adolescents. Quetiapine and divalproex are both useful as monotherapy for the treatment of impulsivity and reactive aggression in adolescents with bipolar and disruptive behavior disorders. Placebo-controlled studies are necessary.