Efficacy and safety of olanzapine for treatment of patients with bipolar depression: Chinese subpopulation analysis of a double-blind, randomized, placebo-controlled study

Background: Depression in bipolar I disorder responds to the atypical antipsychotic olanzapine. This subpopulation analysis assessed whether olanzapine is superior to placebo specifically in the treatment of Chinese patients with bipolar I depression. Methods: This was a subpopulation analysis of a 6-week, multicenter, double-blind, parallel, randomized, placebo-controlled trial among 12 Chinese study centers. Eligible inpatients and outpatients were randomized to olanzapine (5 to 20 mg/day) or placebo. Patients were primarily assessed by the Montgomery-Asberg Depression Rating Scale total score. Secondary assessments used a range of other efficacy and safety measures. This subpopulation analysis was underpowered to show statistically significant differences between treatment groups. Results: In total, 210 patients (mean age 32.9 years at baseline, 54.3% females) were randomized. Similar proportions of patients treated with olanzapine (75.0%) and placebo (72.9%) completed the double-blind phase. Baseline-to-endpoint least-squares mean +/- standard error decrease in the Montgomery-Asberg Depression Rating Scale total score in the olanzapine group (-13.55 +/- 0.80) was similar to that noted in the parent trial (-13.82 +/- 0.65). However, the difference between olanzapine and placebo groups was not statistically significant (P=0.44); this finding was also true for the secondary efficacy measures. A post hoc analysis showed a greater emergence of mania in the placebo group, which likely reduced the treatment difference between olanzapine and placebo in the primary efficacy measure. Safety data were consistent with the known safety profile of olanzapine, including a higher incidence of weight gain (>= 7%) in the olanzapine group (24.1% vs 1.4%, P<0.001). Conclusion: Olanzapine provides similar improvement in depression among Chinese and non-Chinese bipolar I patients. The lack of a statistically significant difference between the olanzapine and placebo groups in this Chinese subpopulation analysis may relate to an a priori lack of study power, and underestimation of the effect of olanzapine because of a greater emergence of mania in placebo-treated patients and missing data associated with a high early discontinuation rate.