Bupropion-SR, Sertraline, or Venlafaxine-XR after Failure of SSRIs for Depression
A. John Rush, M.D., Madhukar H. Trivedi, M.D., Stephen R. Wisniewski, Ph.D., Jonathan W. Stewart, M.D., Andrew A. Nierenberg, M.D., Michael E. Thase, M.D., Louise Ritz, M.B.A., Melanie M. Biggs, Ph.D., Diane Warden, Ph.D., M.B.A., James F. Luther, M.A., Kathy Shores-Wilson, Ph.D., George Niederehe, Ph.D., Maurizio Fava, M.D., for the STAR*D Study Team
Background After unsuccessful treatment for depression witha selective serotonin-reuptake inhibitor (SSRI), it is not knownwhether switching to one antidepressant is more effective thanswitching to another.
Methods We randomly assigned 727 adult outpatients with a nonpsychoticmajor depressive disorder who had no remission of symptoms orcould not tolerate the SSRI citalopram to receive one of thefollowing 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-releasevenlafaxine (250 patients) at a maximal daily dose of 375 mg.The study was conducted in 18 primary and 23 psychiatric caresettings. The primary outcome was symptom remission, definedby a total score of 7 or less on the 17-item Hamilton RatingScale for Depression (HRSD-17) at the end of the study. Scoreson the Quick Inventory of Depressive Symptomatology Self Report (QIDS-SR-16), obtained at treatment visits, determinedsecondary outcomes, including remission (a score of 5 or lessat exit) and response (a reduction of 50 percent or more onbaseline 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-releasebupropion, 17.6 percent and 26.6 percent for sertraline, and24.8 percent and 25.0 percent for extended-release venlafaxine.QIDS-SR-16 response rates were 26.1 percent for sustained-releasebupropion, 26.7 percent for sertraline, and 28.2 percent forextended-release venlafaxine. These treatments did not differsignificantly with respect to outcomes, tolerability, or adverseevents.
Conclusions After unsuccessful treatment with an SSRI, approximatelyone in four patients had a remission of symptoms after switchingto another antidepressant. Any one of the medications in thestudy provided a reasonable second-step choice for patientswith depression. (ClinicalTrials.gov number, NCT00021528
[ClinicalTrials.gov]
.)
Source Information
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{at}utsouthwestern.edu.
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]
Brent, D., Emslie, G., Clarke, G., Wagner, K. D., Asarnow, J. R., Keller, M., Vitiello, B., Ritz, L., Iyengar, S., Abebe, K., Birmaher, B., Ryan, N., Kennard, B., Hughes, C., DeBar, L., McCracken, J., Strober, M., Suddath, R., Spirito, A., Leonard, H., Melhem, N., Porta, G., Onorato, M., Zelazny, J.
(2008). Switching to Another SSRI or to Venlafaxine With or Without Cognitive Behavioral Therapy for Adolescents With SSRI-Resistant Depression: The TORDIA Randomized Controlled Trial. JAMA
299: 901-913
[Abstract][Full Text]
Clayton, P., Auster, T.
(2008). Strategies for the Prevention and Treatment of Suicidal Behavior. Focus
6: 15-21
[Abstract][Full Text]
(2008). Bibliography for Major Depressive Disorder and Suicide. Focus
6: 58-62
[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]
Aikens, J. E., Nease, D. E. Jr, Klinkman, M. S.
(2008). Explaining Patients' Beliefs About the Necessity and Harmfulness of Antidepressants. Ann Fam Med
6: 23-29
[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]
Tinklenberg, J. R., Kraemer, H. C., Yaffe, K., Ross, L., Sheikh, J., Ashford, J. W., Yesavage, J. A., Taylor, J. L.
(2007). Donepezil Treatment and Alzheimer Disease: Can the Results of Randomized Clinical Trials Be Applied to Alzheimer Disease Patients in Clinical Practice?. AJGP
15: 953-960
[Abstract][Full Text]
Haddad, P. M., Anderson, I. M.
(2007). Recognising and managing antidepressant discontinuation symptoms. Adv. Psychiatr. Treat.
13: 447-457
[Abstract][Full Text]
Fink, M., Taylor, M. A.
(2007). Electroconvulsive Therapy: Evidence and Challenges. JAMA
298: 330-332
[Full Text]
Lesperance, F., Frasure-Smith, N.
(2007). Treatment of Depression in Patients With Coronary Artery Disease--Reply. JAMA
297: 1880-1880
[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]
Schramm, E., van Calker, D., Dykierek, P., Lieb, K., Kech, S., Zobel, I., Leonhart, R., Berger, M.
(2007). An Intensive Treatment Program of Interpersonal Psychotherapy Plus Pharmacotherapy for Depressed Inpatients: Acute and Long-Term Results. Am. J. Psychiatry
164: 768-777
[Abstract][Full Text]
Barondes, S. H.
(2007). Melancholia: The Diagnosis, Pathophysiology, and Treatment of Depressive Illness. NEJM
356: 646-647
[Full Text]
Rubino, A., Roskell, N., Tennis, P., Mines, D., Weich, S., Andrews, E.
(2007). Risk of suicide during treatment with venlafaxine, citalopram, fluoxetine, and dothiepin: retrospective cohort study. BMJ
334: 242-242
[Abstract][Full Text]
Ehret, M. J., Chavez, B.
(2006). A Review of the STAR*D Trial. Journal of Pharmacy Practice
19: 353-360
[Abstract]
Nelson, J. C.
(2006). The STAR*D Study: A Four-Course Meal That Leaves Us Wanting More. Am. J. Psychiatry
163: 1864-1866
[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.
(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]
Papakostas, G. I
(2006). Major depressive disorder: similar remission rates with bupropion, sertraline, or venlafaxine following treatment switch from citalopram.. Evid. Based Ment. Health
9: 100-100
[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]
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]
Fava, M., Rush, A. J., Wisniewski, S. R., Nierenberg, A. A., Alpert, J. E., McGrath, P. J., Thase, M. E., Warden, D., Biggs, M., Luther, J. F., Niederehe, G., Ritz, L., Trivedi, M. H., STAR*D StudyTeam,
(2006). A Comparison of Mirtazapine and Nortriptyline Following Two Consecutive Failed Medication Treatments for Depressed Outpatients: A STAR*D Report. Am. J. Psychiatry
163: 1161-1172
[Abstract][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]
Tonks, A.
(2006). What's new in the other general journals.. BMJ
332: 781-782
[Full Text]
Trivedi, M. H., Fava, M., Wisniewski, S. R., Thase, M. E., Quitkin, F., Warden, D., Ritz, L., Nierenberg, A. A., Lebowitz, B. D., Biggs, M. M., Luther, J. F., Shores-Wilson, K., Rush, A. J., the STAR*D Study Team,
(2006). Medication augmentation after the failure of SSRIs for depression.. NEJM
354: 1243-1252
[Abstract][Full Text]
Rubinow, D. R.
(2006). Treatment strategies after SSRI failure--good news and bad news.. NEJM
354: 1305-1307
[Full Text]