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

Background After unsuccessful treatment for depression with a selective serotonin-reuptake inhibitor (SSRI), it is not known whether switching to one antidepressant is more effective than switching to another. Methods We randomly assigned 727 adult outpatients with a nonpsychotic major depressive disorder who had no remission of symptoms or could not tolerate the SSRI citalopram to receive one of the following drugs for up to 14 weeks: sustained-release bupropion (239 patients) at a maximal daily dose of 400 mg, sertraline (238 patients) at a maximal daily dose of 200 mg, or extended-release venlafaxine (250 patients) at a maximal daily dose of 375 mg. The study was conducted in 18 primary and 23 psychiatric care settings. The primary outcome was symptom remission, defined by a total score of 7 or less on the 17-item Hamilton Rating Scale for Depression (HRSD-17) at the end of the study. Scores on the Quick Inventory of Depressive Symptomatology — Self Report (QIDS-SR-16), obtained at treatment visits, determined secondary outcomes, including remission (a score of 5 or less at exit) and response (a reduction of 50 percent or more on baseline scores). Results Remission rates as assessed by the HRSD-17 and the QIDS-SR-16, respectively, were 21.3 percent and 25.5 percent for sustained-release bupropion, 17.6 percent and 26.6 percent for sertraline, and 24.8 percent and 25.0 percent for extended-release venlafaxine. QIDS-SR-16 response rates were 26.1 percent for sustained-release bupropion, 26.7 percent for sertraline, and 28.2 percent for extended-release venlafaxine. These treatments did not differ significantly with respect to outcomes, tolerability, or adverse events. From the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas (A.J.R., M.H.T., M.M.B., D.W., K.S.-W.); the Epidemiology Data Center, Graduate School of Public Health, University of Pittsburgh (S.R.W., J.F.L.), and the Department of Psychiatry, University of Pittsburgh School of Medicine (M.E.T.) — both in Pittsburgh; the New York State Psychiatric Institute and Columbia College of Physicians and Surgeons, New York ( J.W.S.); the Clinical Psychopharmacology Unit, Massachusetts General Hospital, Boston (A.A.N., M.F.); and the National Institute of Mental Health, Bethesda, Md. (L.R., G.N.). Address reprint requests to Dr. Rush at the Department of Psychiatry, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, TX 75390-9086, or at john.rush@utsouthwestern.edu. *The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial investigators are listed in the Appendix. N Engl J Med 2006;354:1231-42. Copyright © 2006 Massachusetts Medical Society. Conclusions After unsuccessful treatment with an SSRI, approximately one in four patients had a remission of symptoms after switching to another antidepressant. Any one of the medications in the study provided a reasonable second-step choice for patients with depression. (ClinicalTrials.gov number, NCT00021528.)