Efficacy and Safety of Second-Generation Antidepressants in the Treatment of Major Depressive Disorder

This study evaluates and compares existing research on the efficacy, effectiveness and common side effects of the most widely-used second-generation antidepressants in the treatment of major depressive disorder. The authors searched MEDLINE, EMBASE, PsychLit, the Cochrane Library and the International Pharmaceutical Abstracts for relevant studies published between 1980 and 2005. They identified 46 randomized controlled trials that directly compared one second-generation antidepressant with another, as well as 24 observational studies and placebo-controlled trials to ascertain side effects.

Key Findings:

  • Eighty-eight percent of the comparative efficacy studies identified reported no significant difference in any outcome measure.
  • Meta-analyses showed a modest additional treatment effect for sertraline and venlafaxine compared with fluoxetine.
  • Limitations in the accuracy of available evidence regarding comparative efficacy and effectiveness of second-generation antidepressants include: potential for publication bias, frequent sponsorship and/or author affiliation with pharmaceutical companies, and the variation in adverse event assessment scales used across studies.