Efficacy of quetiapine monotherapy for the treatment of depressive episodes in bipolar I disorder: A post hoc analysis of combined results from 2 double-blind, randomized, placebo-controlled studies

Objective: To investigate the efficacy and tolerability of quetiapine monotherapy for the treatment of major depressive episodes in patients with bipolar I disorder, as a post hoc analysis of data from 2 large studies, the BipOLar DEpRession (BOLDER) I and II studies, which investigated the overall efficacy of quetiapine in both bipolar I and II disorder. Method: A combined cohort of patients with depressive episodes in bipolar I disorder (DSM-IV criteria) (N = 694) from 2 nearly identical double-blind, randomized, placebo-controlled studies that each randomly assigned patients with bipolar I and II disorder to 8 weeks of treatment with quetiapine 300 or 600 mg/day or placebo was analyzed. The primary efficacy measure was change from baseline to end of treatment (week 8) in the Montgomery-Asberg Depression Rating Scale (MADRS) total scores. Results: In the combined cohort of patients with depressive episodes in bipolar I disorder from 2 studies, there were significantly greater clinical improvements in mean MADRS total scores among patients who received quetiapine compared with placebo from baseline to week I and through week 8 (at week 8: quetiapine 300 mg/day = -19.4; 600 mg/day = -19.6; placebo = -12.6; p <.001 for each dose), providing effect sizes of 0.78 and 0.80, respectively. Changes in MADRS were unrelated to reports of sedation and somnolence. The most common adverse events (AEs) with quetiapine were dry mouth, somnolence, sedation, dizziness, and constipation. Rates of withdrawal because of these AEs were relatively low. Conclusions: Quetiapine monotherapy (300 and 600 mg/day) is more effective than placebo and generally well tolerated for the treatment of depressive episodes in patients with bipolar I disorder.