Medication Augmentation after the Failure of SSRIs for Depression
Madhukar H. Trivedi, M.D., Maurizio Fava, M.D., Stephen R. Wisniewski, Ph.D., Michael E. Thase, M.D., Frederick Quitkin, M.D., Diane Warden, Ph.D., M.B.A., Louise Ritz, M.B.A., Andrew A. Nierenberg, M.D., Barry D. Lebowitz, Ph.D., Melanie M. Biggs, Ph.D., James F. Luther, M.A., Kathy Shores-Wilson, Ph.D., A. John Rush, M.D., for the STAR*D Study Team
Background Although clinicians frequently add a second medicationto an initial, ineffective antidepressant drug, no randomizedcontrolled trial has compared the efficacy of this approach.
Methods We randomly assigned 565 adult outpatients who had nonpsychoticmajor depressive disorder without remission despite a mean of11.9 weeks of citalopram therapy (mean final dose, 55 mg perday) to receive sustained-release bupropion (at a dose of upto 400 mg per day) as augmentation and 286 to receive buspirone(at a dose of up to 60 mg per day) as augmentation. The primaryoutcome of remission of symptoms was defined as a score of 7or less on the 17-item Hamilton Rating Scale for Depression(HRSD-17) at the end of this study; scores were obtained overthe telephone by raters blinded to treatment assignment. The16-item Quick Inventory of Depressive Symptomatology —Self-Report (QIDS-SR-16) was used to determine the secondaryoutcomes of remission (defined as a score of less than 6 atthe end of this study) and response (a reduction in baselinescores of 50 percent or more).
Results The sustained-release bupropion group and the buspironegroup had similar rates of HRSD-17 remission (29.7 percent and30.1 percent, respectively), QIDS-SR-16 remission (39.0 percentand 32.9 percent), and QIDS-SR-16 response (31.8 percent and26.9 percent). Sustained-release bupropion, however, was associatedwith a greater reduction (from baseline to the end of this study)in QIDS-SR-16 scores than was buspirone (25.3 percent vs. 17.1percent, P<0.04), a lower QIDS-SR-16 score at the end ofthis study (8.0 vs. 9.1, P<0.02), and a lower dropout ratedue to intolerance (12.5 percent vs. 20.6 percent, P<0.009).
Conclusions Augmentation of citalopram with either sustained-releasebupropion or buspirone appears to be useful in actual clinicalsettings. Augmentation with sustained-release bupropion doeshave certain advantages, including a greater reduction in thenumber and severity of symptoms and fewer side effects and adverseevents. (ClinicalTrials.gov number, NCT00021528
[ClinicalTrials.gov]
.)
Source Information
From the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas (M.H.T., D.W., M.M.B., K.S.-W., A.J.R.); the Clinical Psychopharmacology Unit, Massachusetts General Hospital, Boston (M.F., A.A.N.); 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 the Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York (F.Q.); and the National Institute of Mental Health, Bethesda, Md. (L.R., B.D.L.).
Address reprint requests to Dr. Trivedi at the Mood Disorder Program and Clinic, Department of Psychiatry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9119, or at madhukar.trivedi{at}utsouthwestern.edu.
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