Bupropion-SR, Sertraline, or Venlafaxine-XR after failure of SSRIs for Depression.


In Level 2 of the STAR-D (Sequenced Treatment Alternatives to Relieve Depression), approximately one in four patients with depression who did not achieve remission with citalopram, had remission of symptoms after switching to one of three other antidepressants: buproprion-SR, sertraline, and extended-release venlafaxine. None of these three treatments differed significantly in outcome measures, adverse effects, or tolerability.


  • N=727 adult outpatients with major depressive disorder without remission despite citalopram therapy randomized to receive up to 14 weeks treatment with one of three drugs:
    • Sustained-release buproprion (n=239)
    • Sertraline (n=238)
    • Extended-release venlafaxine (n=250)
  • Primary outcome: Remission of symptoms as defined by score of 7 or less on 17-item Hamilton Rating Scale for Depression (HRSD-17) at end of study.
  • Secondary outcomes: Self-Report (QIDS-SR-16) used to determine remission (score < 6 at end of study) and response (reduction in baseline scores of 50 percent or more).


  • Remission rates for the three treatments ranged from 17.6% to 26.6%, but did not differ significantly.
  • Response rates ranged from 26.1% to 28.2% but did not differ significantly.
  • No significant difference between the three treatments in terms of adverse events or tolerability.


Rush AJ, Trivedi MH, Wisniewski SR, et al. STAR-D Study Team Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression. N Engl J Med. 2006;354(12):1231–1242.

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