A Double-Blind, Randomized, Placebo-Controlled Trial of Quetiapine Addition in Patients With Obsessive-Compulsive Disorder Refractory to Serotonin Reuptake Inhibitors

Damiaan Denys, M.D.; Femke de Geus, M.A.; Harold J. G. M. van Megen, M.D., Ph.D.; and Herman G. M. Westenberg, Ph.D.

Background: Although serotonin reuptake inhibitors (SRIs) are the most effective pharmacologic treatment currently available for patients with obsessive-compulsive disorder (OCD), 40% to 60% of patients do not respond to this treatment. This study was conducted to evaluate the efficacy and tolerability of quetiapine in addition to an SRI for treatment-refractory patients with OCD.

Method: Forty patients (10 men/30 women, mean +/- SD age = 35.2 +/- 12.1 years; range, 18-60 years) with primary OCD according to DSM-IV criteria who were recruited between February 2001 and December 2002 were randomly assigned in an 8-week, double-blind, placebo-controlled trial to receive dosages titrated upward to 300 mg/day of quetiapine (N = 20) or placebo (N = 20) in addition to their SRI treatment. At entry, all patients were unresponsive to courses of treatment with at least 2 different SRIs at a maximum tolerated dose for 8 weeks. During the study, primary efficacy was assessed according to change from baseline on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). A responder was defined as having a final Clinical Global Impressions-Improvement scale rating of "very much improved" or "much improved" and a decrease of >= 35% in Y-BOCS score.

Results: An intent-to-treat, last-observation-carried-forward analysis demonstrated a mean +/- SD decrease in Y-BOCS score of 9.0 +/- 7.0 (31%) in the quetiapine group and 1.8 +/- 3.4 (7%) in the placebo group (F = 16.99, df = 1,38; p < .001). Eight (40%) of 20 patients in the quetiapine group and 2 (10%) of 20 patients in the placebo group were responders (chi² = 4.8, df = 1, p = .028). The most common side effects in the quetiapine group were somnolence, dry mouth, weight gain, and dizziness.

Conclusion: The results of this study show that quetiapine in addition to an SRI is beneficial for patients with OCD who do not respond to SRI treatment alone.

(J Clin Psychiatry 2004;65:1040-1048)

Received Sept. 3, 2003; accepted Feb. 5, 2004. From the Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Center Utrecht, Utrecht, the Netherlands.

This research was supported by an unrestricted research grant from AstraZeneca, Wilmington, Del.

Corresponding author and reprints: Damiaan Denys, M.D., UMC, (B.01.206), P.O. Box 85500, 3508 GA Utrecht, the Netherlands(e-mail: D.A.J.P.denys@azu.nl).