Comparison of Open-Label,8-Week Trials of Olanzapine Monotherapy and Topiramate Augmentation of Olanzapine for the Treatment of Pediatric Bipolar Disorder

Abstract

Background:

The aim of this study was to test the efficacy and safety of olanzapine + topiramate versus olanzapine monotherapy in the treatment of bipolar disorder (BPD) and treatment-attendant weight gain in children and adolescents.

Method:

Subjects (N = 40) were outpatients of both sexes, 6–17 years of age, with a Diagnostic and Statistical Manual of Mental Disorders, 4^th edition (DSM-IV) diagnosis of BPD (manic, hypomanic, or mixed) and Young Mania Rating Scale (YMRS) total score of >15 treated over 8-week periods in two partially concurrent open-label trials with olanzapine (n = 17) or olanzapine + topiramate (n = 23).

Results:

Subjects in both groups experienced a statistically significant reduction in YMRS scores after 8-week, open-label treatment with olanzapine (baseline YMRS = 26.7 ± 9.5; end-point YMRS = 18.2 ± 12.5, p = 0.04) and olanzapine +topiramate (baseline YMRS = 31.3 ± 7.9; end-point YMRS = 20.4 ± 11.4, p = 0.04). There was no difference in response between the two groups based on YMRS or Clinical Global Impressions–Improvement (CGI-I) scores. Adverse events were few and mild and similar between the two groups, with the exception of weight gain. The weight gain in the olanzapine group was 5.3 ± 2.1 kg and the weight gain in the olanzapine + topiramate group was statistically significantly lower, 2.6 ± 3.6 kg.

Conclusions:

Augmentation of olanzapine with topiramate resulted in a reduced weight gain over the course of an 8-week, open-label trial when compared with olanzapine treatment alone, but did not lead to greater reduction in symptoms of mania.