Efficacy of Risperidone Augmentation to Antidepressants in the Management of Suicidality in Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Pilot Study

Hollis Reeves, B.S.; Sachin Batra, M.D.; Roberta S. May, M.A.; Rusheng Zhang, M.D.; Daniel C. Dahl, M.D.; and Xiaohua Li, M.D., Ph.D.

Objective: Major depressive disorder (MDD) is a severe mental illness with high risk of suicidality. Antidepressant treatment alone is not sufficient for the acute management of risk-taking symptoms of depression. This pilot study was designed to investigate the efficacy of risperidone augmentation to antidepressants in the acute management of suicidality and other core symptoms in MDD with suicidality.

Method: Twenty-four adult men and women diagnosed with MDD (DSM-IV), having a depressive episode with suicidality despite taking an antidepressant, were enrolled in an 8-week double-blind, placebo-controlled study. Subjects were randomly assigned to receive risperidone (0.25-2 mg/day) or placebo while continuing on their antidepressant therapy. Clinical efficacy in suicidality, depressive symptoms, and impulsivity were assessed after treatment with study drugs for 4 days, weekly for 4 weeks, then every other week for 4 weeks. Adverse events were also recorded at each visit. The study was conducted from June 2004 to April 2007.

Results: Risperidone significantly reduced suicidal ideations in MDD patients, and the overall effect of risperidone appeared to be superior to placebo. The effect of risperidone was rapid, with onset at 2 weeks' treatment, and was sustained along the course of 8 weeks' treatment. Furthermore, risperidone demonstrated superiority to placebo in improving other symptoms related to suicidality and having better trial completion rate, and the low dose risperidone was well tolerated by subjects in this study.

Conclusion: Data from this pilot study suggest that risperidone is beneficial as an augmenting treatment in MDD patients who have developed high-risk suicidal ideation during a depressive episode. The antisuicidality effect of risperidone is especially valuable in the acute management of severe depressive symptoms. Although the pilot study is limited by small sample size, the promising results warrant further larger scale investigation in the efficacy of atypical antipsychotics in the treatment of severe depression with suicidality.

Trial Registration: clinicaltrials.gov Identifier: NCT00167154

(J Clin Psychiatry 2008;69:1228-1236. Online Ahead of Print July 29, 2008.)

Received Jan. 28, 2008; accepted May 19, 2008. From the Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham.

This study was supported by an investigator-initiated research fund from Ortho-McNeil Janssen Scientific Affairs, LLC to Dr. Li.

The authors thank all participants for their dedication to psychiatric research; Sherer Boswell, M.A., and Monique Johnson, B.S., for their assistance in research evaluation; and Data Solutions, LLC (Riverdale, N.Y.) for statistical data analysis. Mss. Boswell and Johnson have no pertinent financial or commercial relationships to disclose.

Dr. Li has received grant/research support from the National Institutes of Health (MH064555, MH073723), the National Alliance for Research in Schizophrenia and Depression, Abbott, Shire, Bristol-Myers Squibb, Pfizer, and AstraZeneca. Dr. Dahl has received grant/research support from Pfizer/Organon. Drs. Batra and Zhang and Mss. Reeves and May report no possible conflict of interest, financial or otherwise, related directly or indirectly to the submitted research work.

Corresponding author and reprints: Xiaohua Li, M.D., Ph.D., University of Alabama at Birmingham, 1720 7th Ave. South, Sparks Center 1075C, Birmingham, AL 35294 (e-mail: xili@uab.edu).