Medication augmentation after the failure of SSRIs for depression.


In Level 2 of the STAR-D (Sequenced Treatment Alternatives to Relieve Depression), patients with depression who did not achieve remission with citalopram, may benefit from augmentation with sustained-release buproprion or buspirone. Sustained-release buproprion showed some advantages over buspirone, including better tolerability and greater percent reduction in symptoms.


  • N=565 adult outpatients with major depressive disorder without remission despite citalopram therapy (mean duration: 11.9 weeks, mean final dose: 55 mg/day) randomized to receive:
    • Augmentation therapy with sustained-release buproprion (n=279)
    • Buspirone (n=286)
  • Primary outcome: Remission of symptoms as defined by score of 7 or less on 17-item Hamilton Rating Scale for Depression 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).


  • No significant difference in primary or secondary outcome measures between the two augmentation therapies.
  • Sustained-release buproprion showed a significantly greater reduction in QIDS-SR-16 score (25.3% vs. 17.1%, P<0.04), a lower final QIDS-SD-16 score (8.0 vs. 9.1, P<0.02), and lower dropout rate due to intolerance (12.5% vs. 20.6%, P<0.009).


Trivedi MH, Fava M, Wisniewski SR, et al. Medication augmentation after the failure of SSRIs for depression. N Engl J Med. 2006;354(12):1243–52.

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