Quetiapine in the Treatment of Anxiety in Patients With Bipolar I or II Depression: A Secondary Analysis From a Randomized, Double-Blind, Placebo-Controlled Study

Robert M. A. Hirschfeld, M.D.; Richard H. Weisler, M.D.;Shane R. Raines, M.S.; and Wayne Macfadden, M.D., for the BOLDER Study Group

Objective: Quetiapine monotherapy shows efficacy in bipolar depression. The analyses in this multicenter, double-blind, randomized, fixed-dose, placebo-controlled study evaluated effects of quetiapine monotherapy on anxiety symptoms in bipolar depression.

Method: Of 542 outpatients randomly assigned to treatment, 539 with bipolar I (N = 358) or bipolar II (N = 181) disorder experiencing a major depressive episode (DSM-IV) received 8 weeks of quetiapine monotherapy (600 or 300 mg/day) or placebo between September 2002 and October 2003. Anxiety assessments included the Hamilton Rating Scale for Anxiety (HAM-A) and relevant items from the Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Rating Scale for Depression (HAM-D). Analyses evaluated the pooled dose groups versus placebo.

Results: At week 8, quetiapine 600 and 300 mg/day each demonstrated significant improvements in HAM-A total score versus placebo (-10.8 and -9.9 vs. -6.7, p < .001). Quetiapine (pooled doses) significantly improved HAM-A total score from week 1. In bipolar I depression, quetiapine showed significant improvement in HAM-A total score versus placebo (-10.4 vs. -5.1, p < .001). In bipolar I depression, quetiapine also showed significant improvements versus placebo on the HAM-A anxious mood and tension items, HAM-A psychic and somatic subscales, MADRS inner tension item, and HAM-D psychic anxiety item (all p<.001), but not the HAM-D somatic anxiety item. In bipolar II depression, quetiapine reduced the HAM-A total score more than placebo, but the difference was not statistically significant (-9.8 vs. -9.0, p = .473). In bipolar II depression, quetiapine showed significant improvement versus placebo on the HAM-A anxious mood, MADRS inner tension, and HAM-D psychic anxiety items (all p < .01).

Conclusion: Quetiapine monotherapy shows efficacy in treating anxiety symptoms in bipolar I depression; however, the anxiolytic effects in bipolar II disorder require further investigation.

(J Clin Psychiatry 2006;67:355-362)

Received Oct. 19, 2005; accepted Dec. 28, 2005. From the Department of Psychiatry and Behavioral Sciences, University of Texas Medical Branch, Galveston (Dr. Hirschfeld); Department of Psychiatry and Behavioral Science, Duke University Medical Center and Department of Psychiatry, University of North Carolina Chapel Hill, Raleigh (Dr. Weisler); and AstraZeneca Pharmaceuticals LP, Wilmington, Del. (Mr. Raines and Dr. Macfadden).

This study was supported by AstraZeneca Pharmaceuticals LP, Wilmington, Del. (grant 5077US/0049).

Individual financial disclosure appears at the end of this article.

A complete list of the principal investigators of the BOLDER Study Group appears at the end of this article.

The authors acknowledge the editorial assistance of Michelle O'Donovan, Ph.D., PAREXEL MMS, Uxbridge, U.K. AstraZeneca Pharmaceuticals LP provided financial support for this assistance.

Corresponding author and reprints: Robert M. A. Hirschfeld, M.D., Department of Psychiatry and Behavioral Sciences, University of Texas Medical Branch, 301 University Blvd., Route 0188, Galveston, TX 77555 (e-mail: rohirsch@utmb.edu).