Randomized trial of sertraline versus venlafaxine XR in major depression: efficacy and discontinuation symptoms

J Clin Psychiatry. 2005 Oct;66(10):1312-20. doi: 10.4088/jcp.v66n1015.


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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Ambulatory Care
  • Blood Pressure / drug effects
  • Cyclohexanols / adverse effects
  • Cyclohexanols / therapeutic use*
  • Delayed-Action Preparations
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / psychology
  • Double-Blind Method
  • Female
  • Health Status
  • Humans
  • Male
  • Psychiatric Status Rating Scales
  • Quality of Life
  • Selective Serotonin Reuptake Inhibitors / adverse effects
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Sertraline / adverse effects
  • Sertraline / therapeutic use*
  • Severity of Illness Index
  • Substance Withdrawal Syndrome / diagnosis
  • Substance Withdrawal Syndrome / etiology
  • Treatment Outcome
  • Venlafaxine Hydrochloride


  • Cyclohexanols
  • Delayed-Action Preparations
  • Serotonin Uptake Inhibitors
  • Venlafaxine Hydrochloride
  • Sertraline