Randomised, double-blind, placebo-controlled study of olanzapine in patients with bipolar I depression.

ABSTRACT

BACKGROUND: Atypical antipsychotics are widely used in bipolar mania. However, the efficacy of atypical antipsychotics in bipolar depression has not been comprehensively explored. AIMS: To evaluate olanzapine monotherapy in patients with bipolar depression. METHOD: Patients with bipolar depression received olanzapine (5-20 mg/day, n = 343) or placebo (n = 171) for 6 weeks. The primary outcome was change from baseline to end-point in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Secondary outcomes included Clinical Global Impression - Bipolar Version (CGI-BP) scale, 17-item Hamilton Rating Scale for Depression (HRSD-17) and Young Mania Rating Scale (YMRS) scores, and the rate of response (≥50% reduction in MADRS at end-point), recovery (MADRS ≤12 for ≥4 weeks plus treatment completion) and remission (MADRS ≤8). The trial was registered with ClinicalTrials.gov (NCT00510146). RESULTS: Olanzapine demonstrated significantly greater (P<0.04) improvements on MADRS (least-squares mean change -13.82 v. -11.67), HRSD-17 and YMRS total scores and all CGI-BP subscale scores v. placebo; significantly (P≤0.05) more response and remission, but not recovery; significantly (P<0.01) greater mean increases in weight, fasting cholesterol and triglycerides; and significantly more (P<0.001) patients gained ≥7% body weight. CONCLUSIONS: Olanzapine monotherapy appears to be efficacious in bipolar depression. Additional long-term studies are warranted to confirm these results. Safety findings were consistent with the known safety profile of olanzapine.