A Randomized, Double-Blind, Active-Control Study of Sertraline Versus Venlafaxine XR in Major Depressive Disorder

Richard C. Shelton, M.D.; Kirsten L. Haman, Ph.D.; Mark H. Rapaport, M.D.; Ari Kiev, M.D.; Ward T. Smith, M.D.; Robert M. A. Hirschfeld, M.D.; R. Bruce Lydiard, M.D., Ph.D.; John M. Zajecka, M.D.; and David L. Dunner, M.D.

Objective: Sertraline may produce dual neurotransmitter effects similar to the serotonin-norepinephrine reuptake inhibitors (SNRIs); however, it has been tested against an SNRI in only 1 previous study, and never at an optimal dose. The objective of the current multisite study was to compare relatively higher doses of sertraline (i.e., 150 mg/day) and venlafaxine extended release (XR) (225 mg/day) in outpatients with major depressive disorder.

Method: Subjects with DSM-IV major depressive disorder were randomly assigned to 8 weeks of double-blind treatment with sertraline (N = 82) or venlafaxine XR (N = 78). The study ran from January 2002 through January 2003. The primary outcome measure was the Quality of Life Enjoyment and Satisfaction Questionnaire; secondary outcome variables included the 17-item Hamilton Rating Scale for Depression.

Results: Both treatments led to significant improvement in depressive symptoms and quality-of-life measures. No significant differences were noted between treatment groups for final scores on the primary or secondary measures. The treatment groups did not differ significantly in the percentage of responders (sertraline = 55%, venlafaxine XR = 65%; intent-to-treat [ITT] sample) or remitters (sertraline = 38%, venlafaxine XR = 49%; ITT sample), although the proportions are similar to those found in earlier selective serotonin reuptake inhibitor (SSRI) vs. venlafaxine meta-analyses. In patients who achieved the maximum dose of drug and maintained it for 3 weeks, response rates were similar to those found at lower doses (sertraline = 59%, venlafaxine XR = 70%); however, remission rates for this sample were comparable for both drug groups (sertraline = 48%, venlafaxine XR = 50%).

Conclusions: The efficacies of sertraline and venlafaxine XR were comparable. Although response and remission rates did not differ statistically, the rates were analogous to those reported in previous meta-analyses. However, at clinically relevant higher doses, the remission rates were very similar.

Clinical Trials Registration: ClinicalTrials.gov identifier NCT00179283.

(J Clin Psychiatry 2006;67:1674-1681)

Received Jan. 17, 2006; accepted April 10, 2006. From the Department of Psychiatry, Vanderbilt University Medical Center, Nashville, Tenn. (Drs. Shelton and Haman); the Department of Psychiatry, Cedars-Sinai Medical Center, and the Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, Calif. (Dr. Rapaport); the Social Psychiatry Research Institute, New York, N.Y. (Dr. Kiev); the Summit Research Network, Portland, Ore. (Dr. Smith); the Department of Psychiatry and Behavioral Sciences, University of Texas Medical Branch, Galveston (Dr. Hirschfeld); Southeast Health Consultants, LLC, Charleston, S.C. (Dr. Lydiard); the Department of Psychiatry, Rush University Medical Center, Chicago, Ill. (Dr. Zajecka); and the Department of Psychiatry, Center for Anxiety and Depression, University of Washington, Seattle (Dr. Dunner).

Support for this study was provided by Pfizer Inc, New York, N.Y.

Study data were presented at the 156th annual meeting of the American Psychiatric Association, San Francisco, Calif., May 17-22, 2003; the 42nd annual meeting of the American College of Neuropsychopharmacology, San Juan, Puerto Rico, December 7-11, 2003; and the 44th annual meeting of the New Clinical Drug Evaluation Unit (NCDEU), Phoenix, Ariz., June 1-4, 2004.

Financial disclosure appears at the end of the article.

Corresponding author and reprints: Richard C. Shelton, M.D., 1500 21st Avenue South, Suite 2200, Nashville, TN 37212 (e-mail: richard.shelton@vanderbilt.edu).