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Efficacy of Quetiapine Monotherapy in Bipolar I and II Depression: A Double-blind, Placebo-controlled Study (The BOLDER II Study)

Thase, Michael E. MD*; Macfadden, Wayne MD; Weisler, Richard H. MD; Chang, William PhD; Paulsson, Björn MD§; Khan, Arifulla MD; Calabrese, Joseph R. MDfor the BOLDER II Study Group

Journal of Clinical Psychopharmacology: December 2006 - Volume 26 - Issue 6 - p 600-609
doi: 10.1097/
Original Contributions

This study evaluated the efficacy and tolerability of quetiapine monotherapy for depressive episodes in patients with bipolar I or II disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) who were randomized to 8 weeks of double-blind treatment with quetiapine (300 or 600 mg/d; once daily, evening dosing) or placebo. Patients were assessed weekly using the Montgomery-Åsberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HAM-D). The primary end point was change in MADRS total score from baseline to Week 8 (analysis of covariance/last-observation-carried-forward analysis). Of 509 patients randomized, 59% completed the study. Improvements from baseline in mean MADRS total scores were significantly greater with quetiapine 300 and 600 mg/d than with placebo from first evaluation (Week 1) through Week 8 (both P ≤ 0.001 vs. placebo). Therapeutic effect sizes at Week 8 were 0.61 and 0.54 for quetiapine 300 and 600 mg/d, respectively. Improvements in mean HAM-D scores were also significantly greater with both quetiapine doses than with placebo (P < 0.001) as early as Week 1 and throughout the study. The MADRS response and remission rates were also significantly greater in both quetiapine dose groups compared with placebo. Improvements in primary and secondary outcomes were observed with both 300 and 600 mg/d quetiapine without major differences between the doses. Common adverse events included dry mouth, sedation, somnolence, dizziness, and constipation. The incidence of treatment-emergent mania or hypomania was lower with quetiapine treatment than placebo. This study demonstrates that quetiapine monotherapy is an effective and well-tolerated treatment for depressive episodes in bipolar disorder, confirming the results observed from a previous study (BipOLar DEpRession [BOLDER] I).

*Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, PA; †AstraZeneca Pharmaceuticals LP, Wilmington, DE; ‡Duke University Medical Center, University of North Carolina, Chapel Hill, NC; §AstraZeneca, Södertälje, Sweden; ∥Northwest Clinical Research Center, Bellevue, WA and ¶University Hospitals of Cleveland, Case University School of Medicine, Cleveland, OH.

Received April 12, 2006; accepted after revision September 27, 2006.

Dr. Wayne Macfadden is now a former employee of AstraZeneca Pharmaceuticals LP.

This study (D1447C00135) was supported by AstraZeneca Pharmaceuticals LP.

Address correspondence and reprint requests to: Michael E. Thase, MD, Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, 3811 O'Hara Street, Pittsburgh, PA 15213-2593. E-mail:

© 2006 Lippincott Williams & Wilkins, Inc.