Randomized Trial of Sertraline Versus Venlafaxine XR in Major Depression: Efficacy and Discontinuation Symptoms

Aytekin Sir, M.D.; Russell F. D'Souza, M.D., M.P.M.; Sukru Uguz, M.D.; Tom George, D.P.M., M.R.C.Psych., F.R.A.N.Z.C.P.; Simavi Vahip, M.D.; Malcolm Hopwood, M.D., M.P.M., F.R.A.N.Z.C.P.; Andrew J. Martin, Ph.D.; William Lam, M.D., Ph.D.; and Tal Burt, M.D.

Background: The comparative efficacy of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) was recently debated. Meta-analyses, based mainly on fluoxetine comparator data, suggest that the SNRI venlafaxine has superior efficacy to SSRIs in treatment of major depression.

Objective: To compare quality of life (QOL), efficacy, safety, and tolerability associated with sertraline and venlafaxine extended release (XR) for treatment of DSM-IV major depression.

Method: This was an 8-week, double-blind, randomized study of sertraline (50-150 mg/day) versus venlafaxine XR (75-225 mg/day), followed by a 2-week taper period. Subjects were recruited from 7 sites in Turkey and 6 sites in Australia between October 2002 and July 2003. The primary outcome measure was the Quality of Life Enjoyment and Satisfaction Questionnaire. Secondary outcome measures included measures of depression (including response and remission), anxiety, pain, safety (e.g., blood pressure), and tolerability (e.g., discontinuation symptoms).

Results: A total of 163 subjects received study treatment (women, 69%; mean age, 37.0 [SD = 12.9] years). No significant differences in QOL or efficacy were noted between treatments on the primary or secondary endpoints for the total study population or the anxious depression and severe depression subgroups. A priori analyses of symptoms associated with treatment discontinuation demonstrated no difference between treatment groups. However, in post hoc analyses, sertraline was associated with less burden of moderate to severe discontinuation symptoms. Venlafaxine XR was associated with a relative increase in mean blood pressure (supine diastolic blood pressure, -4.4 mm Hg difference at week 8/last observation carried forward).

Conclusion: Sertraline and venlafaxine XR demonstrated comparable effects on QOL and efficacy in treatment of major depression, although sertraline may be associated with a lower symptom burden during treatment discontinuation and a reduced risk of blood pressure increase.

(J Clin Psychiatry 2005;66:1312-1320)

Received Sept. 17, 2004; accepted March 28, 2005. From the Department of Psychiatry, Dicle University Medical Faculty, Diyarbakir, Turkey (Dr. Sir); the Mental Health Research Institute of Victoria, Box Hill, Victoria, Australia (Dr. D'Souza); the Department of Psychiatry, Cukurova University Medical Faculty, Adana, Turkey (Dr. Uguz); the Northwest Specialist Centre, Everton Park, Queensland, Australia (Dr. George); the Department of Psychiatry, Ege University Medical Faculty, Izmir, Turkey (Dr. Vahip); the Veterans' Psychiatry Unit, Austin & Repatriation Medical Centre, West Heidelberg, Victoria, Australia (Dr. Hopwood); the Asia Biometrics Centre, Pfizer Worldwide Development Operations, Sydney, Australia (Dr. Martin); Pfizer Australia Pty, Ltd., Sydney, Australia (Dr. Lam); Pfizer Inc, New York, N.Y.; and the Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, N.Y. (Dr. Burt).

This study was funded by Pfizer Inc.

Financial disclosure appears at the end of this article.

Acknowledgment appears at the end of the article.

Corresponding author and reprints: Aytekin Sir, M.D., Dicle University Medical Faculty, Department of Psychiatry, Diyarbakir, Turkey (e-mail: asir@dicle.edu.tr).