Early Treatment Response in Alcohol Dependence With Extended-Release Naltrexone

Domenic A. Ciraulo, M.D.; Qunming Dong, Ph.D.; Bernard L. Silverman, M.D.; David R. Gastfriend, M.D.; and Helen M. Pettinati, Ph.D.

Objective: We sought to determine the time course for onset of effect of intramuscular injectable extended-release naltrexone (XR-NTX), which has demonstrated efficacy for alcohol dependence.

Method: A post hoc analysis of a randomized, double-blind, placebo-controlled, multicenter study was conducted. In the study, actively drinking men and women who met DSM-IV-TR criteria for alcohol dependence were randomly assigned to receive injections of XR-NTX 380 mg (N = 205) or 190 mg (N = 210) or placebo (N = 209) every 4 weeks for 24 weeks. Patients also received 12 sessions of standardized, low-intensity psychosocial intervention. Drinking data were analyzed by month and, during the first month, by day to explore the time course for onset of effect on heavy drinking days in patients receiving XR-NTX versus placebo. The study data were collected between February 2002 and September 2003.

Results: During the first month following injection, patients receiving XR-NTX 380 mg had 37% fewer heavy drinking days versus placebo (p < .01). By day 2, a significant reduction in the median number of drinks consumed per day was observed in patients given XR-NTX 380 mg compared with placebo (p < .05). By day 3, XR-NTX 380 mg resulted in a significant reduction in the percentage of patients reporting heavy drinking compared with placebo (p < .05); this reduction was maintained throughout the study. A dose-response effect was observed, with intermediate results for XR-NTX 190 mg.

Conclusion: XR-NTX 380 mg provided a rapid onset of therapeutic effect in the first 2 days after the first injection that was sustained throughout the 24-week trial. Potential clinical implications of the rapid, early onset of effect of this medication's delivery system for patients who are dependent on alcohol include facilitation of early engagement in treatment, motivation to continue treatment, and focus on the goals established in counseling.

(J Clin Psychiatry 2008;69:190-195; online ahead of print January 9, 2008)

Received Feb. 23, 2007; accepted July 3, 2007. From the Division of Psychiatry, Boston University School of Medicine, Boston, Mass. (Dr. Ciraulo); Alkermes, Inc., Cambridge, Mass. (Drs. Dong, Silverman, and Gastfriend); and Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia (Dr. Pettinati).

This study was sponsored by Alkermes, Inc., Cambridge, Mass., and Cephalon, Inc., Frazer, Pa. Writing support was provided by Embryon, Somerville, N.J.

Acknowledgments appear at the end of the article.

Dr. Ciraulo has received grant and research support from Alkermes, Inc., AstraZeneca, Catalyst Pharmaceutical Partners, Bristol-Myers Squibb, Drug Abuse Sciences, Janssen, Lipha, Ortho-McNeil, and UCB Pharma; has served as a consultant to Bristol-Myers Squibb, Cephalon, Janssen, and Ortho-McNeil; and has served on the advisory boards for Alkermes, Inc., Cephalon, and Ortho-McNeil. Drs. Dong, Silverman, and Gastfriend are employees of Alkermes, Inc. Dr. Pettinati has received grant and research support from Alkermes, Inc., Bristol-Myers Squibb, Cephalon, Forest, and Ortho-McNeil and has served as a consultant to and on the advisory boards and speakers bureaus for Alkermes, Inc., Cephalon, and Forest. Dr. Pettinati discloses that neither she nor her family owns any stock in any of the aforementioned companies.

Corresponding author and reprints: Domenic A. Ciraulo, M.D., Division of Psychiatry, Boston University School of Medicine, 720 Harrison Ave., Doctor's Office Bldg., Room 914, Boston, MA 02118-2393 (e-mail: dciraulo@bu.edu).