Prevention of Recurrent Episodes of Depression With Venlafaxine ER in a 1-Year Maintenance Phase From the PREVENT Study

James H. Kocsis, M.D.; Michael E. Thase, M.D.; Madhukar H. Trivedi, M.D.; Richard C. Shelton, M.D.; Susan G. Kornstein, M.D.; Charles B. Nemeroff, M.D., Ph.D.; Edward S. Friedman, M.D.; Alan J. Gelenberg, M.D.; David L. Dunner, M.D.; Robert M. A. Hirschfeld, M.D.; Anthony J. Rothschild, M.D.; James M. Ferguson, M.D.; Alan F. Schatzberg, M.D.; John M. Zajecka, M.D.; Ronald D. Pedersen, M.S.; Bing Yan, M.D.; Saeed Ahmed, M.D.; Jeff Musgnung, M.T.; Philip T. Ninan, M.D.; and Martin B. Keller, M.D.

Objectives: To test the long-term efficacy and safety of venlafaxine extended-release (ER) in preventing recurrence in patients with major depression.

Method: This multiple-phase study, entitled "Prevention of Recurrent Episodes of Depression With Venlafaxine for Two Years" (PREVENT), was conducted from December 2000 through July 2005 in patients with recurrent unipolar depression (DSM-IV) who were initially randomly assigned to double-blind treatment with venlafaxine ER (75 mg/day to 300 mg/day) or fluoxetine (20 mg/day to 60 mg/day) for 10 weeks of acute treatment. Responders then received 6 months of continuation treatment. Those who remained responders were then enrolled into a 12-month maintenance period. Venlafaxine ER responders were randomly assigned to receive double-blind treatment with venlafaxine ER or placebo. Fluoxetine responders were not randomly assigned but continued taking fluoxetine in order to maintain the blind during the maintenance study. Time to recurrence of depression (17-item Hamilton Rating Scale for Depression total score > 12 and < 50% reduction from acute phase baseline) with venlafaxine ER versus that of placebo were compared.

Results: The efficacy evaluable sample consisted of 129 patients in each group. The mean daily dose of venlafaxine ER was 224.7 mg (SD = 66.7). The cumulative probability of recurrence through 12 months, based on the primary definition, was 23.1% (95% CI = 15.3 to 30.9) for venlafaxine ER and 42.0% (95% CI = 31.8 to 52.2) for placebo (p = .005, log-rank test).

Conclusion: Patients who had been successfully treated with venlafaxine ER during acute and continuation therapy were significantly less likely to experience recurrence with venlafaxine ER than with placebo over a 12-month maintenance treatment period.

Clinical Trials Registration: ClinicalTrials.gov identifier NCT00046020.

(J Clin Psychiatry 2007;68:1014-1023)

Received Dec. 13, 2006; accepted March 29, 2007. From the Department of Psychiatry, Weill Cornell Medical College, New York, N.Y. (Dr. Kocsis); Department of Psychiatry, University of Pennsylvania, Philadelphia (Dr. Thase); Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pa. (Dr. Friedman); Department of Psychiatry, University of Texas Southwestern Medical School, Dallas (Dr. Trivedi); Department of Psychiatry, Vanderbilt University, Nashville, Tenn. (Dr. Shelton); Institute for Women's Health, Department of Psychiatry, and Mood Disorders Institute, Virginia Commonwealth University Medical Center, Richmond (Dr. Kornstein); Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Ga. (Dr. Nemeroff); Department of Psychiatry, University of Arizona, Tucson (Dr. Gelenberg); the Center for Anxiety and Depression, University of Washington-Seattle, Mercer Island (Dr. Dunner); Department of Psychiatry, University of Texas Medical Branch, Galveston (Dr. Hirschfeld); Department of Psychiatry, University of Massachusetts Medical School and UMass Memorial Health Care, Worcester (Dr. Rothschild); Department of Psychiatry, University of Utah Medical School, Salt Lake City (Dr. Ferguson); Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif. (Dr. Schatzberg); Department of Psychiatry, Rush University Medical Center, Chicago, Ill. (Dr. Zajecka); Wyeth Pharmaceuticals, Collegeville, Pa. (Drs. Yan, Ahmed, and Ninan and Messrs. Pedersen and Musgnung); and Department of Psychiatry and Human Behavior, Brown University, Providence, R.I. (Dr. Keller).

This clinical trial and analysis were sponsored by Wyeth Research, Collegeville, Pa. Funding provided by Wyeth Research. Drs. Yan, Ahmed, and Ninan and Messrs. Pedersen and Musgnung are employees of Wyeth Research.

A list of previous presentations of data appears at the end of the article.

The authors wish to thank Sherri D. Jones, Pharm.D., Jennifer B. Hutcheson, and Lorraine M. Sweeney of Medesta Publications, a business of ADVOGENT, for their writing and editorial assistance.

Financial disclosure appears at the end of the article.

Corresponding author and reprints: James H. Kocsis, M.D., Weill Cornell Medical College, 525 East 68th St., New York, NY 10012 (e-mail: Jhk2002@med.cornell.edu).