Risperidone and Haloperidol Augmentation of Serotonin Reuptake Inhibitors in Refractory Obsessive-Compulsive Disorder: A Crossover Study

Xiaohua Li, M.D., Ph.D.; Roberta S. May, M.A.; Lelland C. Tolbert, Ph.D.; Warren T. Jackson, Ph.D.; James M. Flournoy, Jr., Ph.D.; and Lewis R. Baxter, Jr., M.D.

Background: Although serotonin reuptake inhibitors (SRIs) are the first-line treatment for obsessive-compulsive disorder (OCD), approximately half of patients with OCD do not respond adequately to SRI monotherapy. Patients with predominant obsessions are common in OCD and are often difficult to treat, necessitating adjunctive treatment.

Method: This was a 9-week, double-blind, placebo-controlled, crossover study comparing the benefits of 2-week adjunctive treatments with risperidone, haloperidol, and placebo in patients with OCD (DSM-IV criteria) who continued to have severe symptoms despite taking a stable dose of an SRI. Eligible patients must have been receiving a therapeutic dose of an SRI for at least 12 weeks and at the screening visit had a score >=10 on items 1-5 (obsession) and a total score >=16 on the Yale-Brown Obsessive Compulsive Scale (YBOCS). Data were collected from January 1999 through April 2002.

Results: Sixteen patients were enrolled and 12 completed the study. On the YBOCS, both risperidone and haloperidol significantly reduced obsession (p < .05) when compared with placebo. There was a tendency that haloperidol, and to a lesser degree risperidone, also reduced the compulsion and the total YBOCS scores. These results were accompanied by a reduction in the Hopkins Symptom Checklist 90-revised (SCL-90R) anxiety scale score. According to the 17-item Hamilton Rating Scale for Depression, the SCL-90R depression scale, and the Profile of Mood States, risperidone, but not haloperidol, also improved depressed mood. Neither risperidone nor haloperidol changed neurocognitive function during the 2-week treatment. All 12 patients completed the 2-week risperidone treatment, but 5 of the 12 terminated haloperidol treatment early owing to intolerable side effects.

Conclusion: Adjunctive risperidone improved obsessions and depressed mood and was well tolerated in patients with SRI-refractory OCD.

(J Clin Psychiatry 2005;66:736-743)

Received July 28, 2004; accepted Nov. 15, 2004. From the Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham (Drs. Li, Tolbert, Jackson, and Flournoy and Ms. May); and the Department of Psychiatry, University of Florida, Gainesville (Dr. Baxter).

This study was supported by Janssen Pharmaceutica Products, L.P.

Dr. Baxter has been a consultant for, received grant/research support and honoraria from, and participated in speakers/advisory boards for Janssen.

The authors thank S. Taylor Williams, B.S., and Ari B. Friedman for data processing and Alfred A. Bartolucci, Ph.D., for data analysis.

Corresponding author and reprints: Xiaohua Li, M.D., Ph.D., UAB-Psychiatry, 213 Smolian, 1700 7th Avenue South, Birmingham, AL 35294 (e-mail: xili@uab.edu).