FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 354:1243-1252 March 23, 2006 Number 12 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

Background Although clinicians frequently add a second medication to an initial, ineffective antidepressant drug, no randomized controlled trial has compared the efficacy of this approach.

Methods We randomly assigned 565 adult outpatients who had nonpsychotic major depressive disorder without remission despite a mean of 11.9 weeks of citalopram therapy (mean final dose, 55 mg per day) to receive sustained-release bupropion (at a dose of up to 400 mg per day) as augmentation and 286 to receive buspirone (at a dose of up to 60 mg per day) as augmentation. The primary outcome of remission of symptoms was defined as a score of 7 or less on the 17-item Hamilton Rating Scale for Depression (HRSD-17) at the end of this study; scores were obtained over the telephone by raters blinded to treatment assignment. The 16-item Quick Inventory of Depressive Symptomatology — Self-Report (QIDS-SR-16) was used to determine the secondary outcomes of remission (defined as a score of less than 6 at the end of this study) and response (a reduction in baseline scores of 50 percent or more).

Results The sustained-release bupropion group and the buspirone group had similar rates of HRSD-17 remission (29.7 percent and 30.1 percent, respectively), QIDS-SR-16 remission (39.0 percent and 32.9 percent), and QIDS-SR-16 response (31.8 percent and 26.9 percent). Sustained-release bupropion, however, was associated with a greater reduction (from baseline to the end of this study) in QIDS-SR-16 scores than was buspirone (25.3 percent vs. 17.1 percent, P<0.04), a lower QIDS-SR-16 score at the end of this study (8.0 vs. 9.1, P<0.02), and a lower dropout rate due to intolerance (12.5 percent vs. 20.6 percent, P<0.009).

Conclusions Augmentation of citalopram with either sustained-release bupropion or buspirone appears to be useful in actual clinical settings. Augmentation with sustained-release bupropion does have certain advantages, including a greater reduction in the number and severity of symptoms and fewer side effects and adverse events. (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.

Full Text of this Article

Related Letters:

Depression — Augmentation or Switch after Initial SSRI Treatment
Sussman N., Williams S. C., Tebartz van Elst L., Ebert D., Hesslinger B., Rush A. J., Trivedi M. H., Wisniewski S. R., the STAR*D trial investigators , Rubinow D. R.
Extract | Full Text | PDF  
N Engl J Med 2006; 354:2611-2613, Jun 15, 2006. Correspondence

This article has been cited by other articles:

• Kroenke, K., Bair, M. J., Damush, T. M., Wu, J., Hoke, S., Sutherland, J., Tu, W. (2009). Optimized Antidepressant Therapy and Pain Self-management in Primary Care Patients With Depression and Musculoskeletal Pain: A Randomized Controlled Trial. JAMA 301: 2099-2110 [Abstract] [Full Text]  
• Wang, P. S., Ulbricht, C. M., Schoenbaum, M. (2009). Improving Mental Health Treatments Through Comparative Effectiveness Research. Health Aff (Millwood) 28: 783-791 [Abstract] [Full Text]  
• Carney, R. M., Freedland, K. E. (2009). Treatment-Resistant Depression and Mortality After Acute Coronary Syndrome. Am. J. Psychiatry 166: 410-417 [Abstract] [Full Text]  
• Lesser, I., Zisook, S., Flores, D., Sciolla, A., Wisniewski, S., Cook, I., Epstein, M., Rosales, A., Gonzalez, C., Trivedi, M., Luther, J., Alpert, J., Rush, A. J. (2008). Depression Outcomes of Spanish- and English-Speaking Hispanic Outpatients in STAR*D. Psychiatr. Serv. 59: 1273-1284 [Abstract] [Full Text]  
• Hatcher, S. (2008). The STAR*D trial: the 300 lb gorilla is in the room, but does it block all the light?. Evid. Based Ment. Health 11: 97-99 [Full Text]  
• Weinberger, M. I., Sirey, J. A., Bruce, M. L., Heo, M., Papademetriou, E., Meyers, B. S. (2008). Predictors of Major Depression Six Months After Admission for Outpatient Treatment. Psychiatr. Serv. 59: 1211-1215 [Abstract] [Full Text]  
• (2008). Practice Parameter for the Assessment and Treatment of Children and Adolescents With Depressive Disorders. Focus 6: 379-400 [Abstract] [Full Text]  
• Anderson, I., Ferrier, I., Baldwin, R., Cowen, P., Howard, L, Lewis, G, Matthews, K, McAllister-Williams, R., Peveler, R., Scott, J, Tylee, A (2008). Evidence-based guidelines for treating depressive disorders with antidepressants: A revision of the 2000 British Association for Psychopharmacology guidelines. J Psychopharmacol 22: 343-396 [Abstract]  
• Rush, A. J. MD (2008). Developing the evidence for evidence-based practice. CMAJ 178: 1313-1315 [Full Text]  
• Fava, M., Rush, A. J., Alpert, J. E., Balasubramani, G. K., Wisniewski, S. R., Carmin, C. N., Biggs, M. M., Zisook, S., Leuchter, A., Howland, R., Warden, D., Trivedi, M. H. (2008). Difference in Treatment Outcome in Outpatients With Anxious Versus Nonanxious Depression: A STAR*D Report. Am. J. Psychiatry 165: 342-351 [Abstract] [Full Text]  
• (2008). Bibliography for Major Depressive Disorder and Suicide. Focus 6: 58-62 [Full Text]  
• (2008). Abstracts For Major Depressive Disorder and Suicide. Focus 6: 63-68 [Full Text]  
• Thase, M. E., Friedman, E. S., Biggs, M. M., Wisniewski, S. R., Trivedi, M. H., Luther, J. F., Fava, M., Nierenberg, A. A., McGrath, P. J., Warden, D., Niederehe, G., Hollon, S. D., Rush, A. J. (2008). Cognitive Therapy Versus Medication in Augmentation and Switch Strategies as Second-Step Treatments: A STAR*D Report. Focus 6: 104-119 [Abstract] [Full Text]  
• Rush, A. J., Trivedi, M. H., Wisniewski, S. R., Nierenberg, A. A., Stewart, J. W., Warden, D., Niederehe, G., Thase, M. E., Lavori, P. W., Lebowitz, B. D., McGrath, P. J., Rosenbaum, J. F., Sackeim, H. A., Kupfer, D. J., Luther, J., Fava, M. (2008). Acute and Longer-Term Outcomes in Depressed Outpatients Requiring One or Several Treatment Steps: A STAR*D Report. Focus 6: 128-142 [Abstract] [Full Text]  
• Unutzer, J. (2007). Late-Life Depression. NEJM 357: 2269-2276 [Full Text]  
• Mahmoud, R. A., Pandina, G. J., Turkoz, I., Kosik-Gonzalez, C., Canuso, C. M., Kujawa, M. J., Gharabawi-Garibaldi, G. M. (2007). Risperidone for Treatment-Refractory Major Depressive Disorder: A Randomized Trial. ANN INTERN MED 147: 593-602 [Abstract] [Full Text]  
• Paddock, S., Laje, G., Charney, D., Rush, A. J., Wilson, A. F., Sorant, A. J.M., Lipsky, R., Wisniewski, S. R., Manji, H., McMahon, F. J. (2007). Association of GRIK4 With Outcome of Antidepressant Treatment in the STAR*D Cohort. Am. J. Psychiatry 164: 1181-1188 [Abstract] [Full Text]  
• Carey, T. S., Williams, J. W. Jr., Melvin, C., Oldham, J., Goodman, F. (2007). Best Practices: Comparing Medication Treatments in Mental Health: Drug Class Reviews and Policy Challenges. Psychiatr. Serv. 58: 746-748 [Abstract] [Full Text]  
• Schultz, S. K. (2007). Depression in the Older Adult: The Challenge of Medical Comorbidity. Am. J. Psychiatry 164: 847-848 [Full Text]  
• Dew, M. A., Whyte, E. M., Lenze, E. J., Houck, P. R., Mulsant, B. H., Pollock, B. G., Stack, J. A., Bensasi, S., Reynolds, C. F. III (2007). Recovery From Major Depression in Older Adults Receiving Augmentation of Antidepressant Pharmacotherapy. Am. J. Psychiatry 164: 892-899 [Abstract] [Full Text]  
• Weissman, M. M. (2007). Cognitive Therapy and Interpersonal Psychotherapy: 30 Years Later. Am. J. Psychiatry 164: 693-696 [Full Text]  
• Thase, M. E., Friedman, E. S., Biggs, M. M., Wisniewski, S. R., Trivedi, M. H., Luther, J. F., Fava, M., Nierenberg, A. A., McGrath, P. J., Warden, D., Niederehe, G., Hollon, S. D., Rush, A. J. (2007). Cognitive Therapy Versus Medication in Augmentation and Switch Strategies as Second-Step Treatments: A STAR*D Report. Am. J. Psychiatry 164: 739-752 [Abstract] [Full Text]  
• Barondes, S. H. (2007). Melancholia: The Diagnosis, Pathophysiology, and Treatment of Depressive Illness. NEJM 356: 646-647 [Full Text]  
• Ehret, M. J., Chavez, B. (2006). A Review of the STAR*D Trial. Journal of Pharmacy Practice 19: 353-360 [Abstract]  
• Rush, A. J., Trivedi, M. H., Wisniewski, S. R., Nierenberg, A. A., Stewart, J. W., Warden, D., Niederehe, G., Thase, M. E., Lavori, P. W., Lebowitz, B. D., McGrath, P. J., Rosenbaum, J. F., Sackeim, H. A., Kupfer, D. J., Luther, J., Fava, M. (2006). Acute and Longer-Term Outcomes in Depressed Outpatients Requiring One or Several Treatment Steps: A STAR*D Report. Am. J. Psychiatry 163: 1905-1917 [Abstract] [Full Text]  
• (2006). Other articles noted. Evid. Based Ment. Health 9: 92-92 [Full Text]  
• Zisook, S. (2006). Ask the Expert PSYCHOPHARMACOLOGY: MAJOR DEPRESSIVE DISORDER. Focus 4: 484- [Full Text]  
• Valenstein, M. (2006). Keeping Our Eyes on STAR{star}D. Focus 4: 522- [Full Text]  
• Menza, M. (2006). STAR{star}D: The Results Begin to Roll in. Focus 4: 525- [Full Text]  
• Valenstein, M. (2006). Keeping Our Eyes on STAR*D. Am. J. Psychiatry 163: 1484-1486 [Full Text]  
• Nierenberg, A. A., Fava, M., Trivedi, M. H., Wisniewski, S. R., Thase, M. E., McGrath, P. J., Alpert, J. E., Warden, D., Luther, J. F., Niederehe, G., Lebowitz, B., Shores-Wilson, K., Rush, A. J., STAR*D Study Team, (2006). A Comparison of Lithium and T3 Augmentation Following Two Failed Medication Treatments for Depression: A STAR*D Report. Am. J. Psychiatry 163: 1519-1530 [Abstract] [Full Text]  
• McGrath, P. J., Stewart, J. W., Fava, M., Trivedi, M. H., Wisniewski, S. R., Nierenberg, A. A., Thase, M. E., Davis, L., Biggs, M. M., Shores-Wilson, K., Luther, J. F., Niederehe, G., Warden, D., Rush, A. J., STAR*D Study Team, (2006). Tranylcypromine Versus Venlafaxine Plus Mirtazapine Following Three Failed Antidepressant Medication Trials for Depression: A STAR*D Report. Am. J. Psychiatry 163: 1531-1541 [Abstract] [Full Text]  
• (2006). Other articles noted. Evid. Based Ment. Health 9: 64-64 [Full Text]  
• Bauer, M. S., McBride, L., Williford, W. O., Glick, H., Kinosian, B., Altshuler, L., Beresford, T., Kilbourne, A. M., Sajatovic, M., and Coauthors for the Cooperative Studies Program, (2006). Collaborative Care for Bipolar Disorder: Part I. Intervention and Implementation in a Randomized Effectiveness Trial. Psychiatr. Serv. 57: 927-936 [Abstract] [Full Text]  
• Bauer, M. S., McBride, L., Williford, W. O., Glick, H., Kinosian, B., Altshuler, L., Beresford, T., Kilbourne, A. M., Sajatovic, M., and Coauthors for the Cooperative Studies Program, (2006). Collaborative Care for Bipolar Disorder: Part II. Impact on Clinical Outcome, Function, and Costs. Psychiatr. Serv. 57: 937-945 [Abstract] [Full Text]  
• Menza, M. (2006). STAR*D: The Results Begin to Roll in. Am. J. Psychiatry 163: 1123-1123 [Full Text]  
• Sussman, N., Williams, S. C., Tebartz van Elst, L., Ebert, D., Hesslinger, B., Rush, A. J., Trivedi, M. H., Wisniewski, S. R., the STAR*D trial investigators, , Rubinow, D. R. (2006). Depression--augmentation or switch after initial SSRI treatment.. NEJM 354: 2611-2613 [Full Text]  
• (2006). Multiple Levels of Drug Treatment for Depression. Journal Watch Dermatology 2006: 9-9 [Full Text]  
• (2006). When an SSRI Fails. JWatch Women's Health 2006: 8-8 [Full Text]  
• (2006). Multiple Levels of Drug Treatment for Depression. JWatch General 2006: 5-5 [Full Text]  
• (2006). What to Do After Depressed Patients Fail an SSRI. JWatch Psychiatry 2006: 1-1 [Full Text]  
• Rush, A. J., Trivedi, M. H., Wisniewski, S. R., Stewart, J. W., Nierenberg, A. A., Thase, M. E., Ritz, L., Biggs, M. M., Warden, D., Luther, J. F., Shores-Wilson, K., Niederehe, G., Fava, M., the STAR*D Study Team, (2006). Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression.. NEJM 354: 1231-1242 [Abstract] [Full Text]  
• Rubinow, D. R. (2006). Treatment strategies after SSRI failure--good news and bad news.. NEJM 354: 1305-1307 [Full Text]