Medication augmentation after the failure of SSRIs for depression

Madhukar H. Trivedi, Maurizio Fava, Stephen R. Wisniewski, Michael E. Thase, Frederick Quitkin, Diane Warden, Louise Ritz, Andrew A. Nierenberg, Barry D. Lebowitz, Melanie M. Biggs, James F. Luther, Kathy Shores-Wilson, A. John Rush

Research output: Contribution to journalArticle

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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).

Original languageEnglish (US)
Pages (from-to)1243-1252
Number of pages10
JournalNew England Journal of Medicine
Volume354
Issue number12
DOIs
StatePublished - Mar 23 2006

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Bupropion
Buspirone
Depression
Citalopram
Major Depressive Disorder
Telephone
Self Report
Antidepressive Agents
Outpatients
Randomized Controlled Trials
Equipment and Supplies
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Trivedi, M. H., Fava, M., Wisniewski, S. R., Thase, M. E., Quitkin, F., Warden, D., ... Rush, A. J. (2006). Medication augmentation after the failure of SSRIs for depression. New England Journal of Medicine, 354(12), 1243-1252. https://doi.org/10.1056/NEJMoa052964

Medication augmentation after the failure of SSRIs for depression. / Trivedi, Madhukar H.; Fava, Maurizio; Wisniewski, Stephen R.; Thase, Michael E.; Quitkin, Frederick; Warden, Diane; Ritz, Louise; Nierenberg, Andrew A.; Lebowitz, Barry D.; Biggs, Melanie M.; Luther, James F.; Shores-Wilson, Kathy; Rush, A. John.

In: New England Journal of Medicine, Vol. 354, No. 12, 23.03.2006, p. 1243-1252.

Research output: Contribution to journalArticle

Trivedi, MH, Fava, M, Wisniewski, SR, Thase, ME, Quitkin, F, Warden, D, Ritz, L, Nierenberg, AA, Lebowitz, BD, Biggs, MM, Luther, JF, Shores-Wilson, K & Rush, AJ 2006, 'Medication augmentation after the failure of SSRIs for depression', New England Journal of Medicine, vol. 354, no. 12, pp. 1243-1252. https://doi.org/10.1056/NEJMoa052964
Trivedi MH, Fava M, Wisniewski SR, Thase ME, Quitkin F, Warden D et al. Medication augmentation after the failure of SSRIs for depression. New England Journal of Medicine. 2006 Mar 23;354(12):1243-1252. https://doi.org/10.1056/NEJMoa052964
Trivedi, Madhukar H. ; Fava, Maurizio ; Wisniewski, Stephen R. ; Thase, Michael E. ; Quitkin, Frederick ; Warden, Diane ; Ritz, Louise ; Nierenberg, Andrew A. ; Lebowitz, Barry D. ; Biggs, Melanie M. ; Luther, James F. ; Shores-Wilson, Kathy ; Rush, A. John. / Medication augmentation after the failure of SSRIs for depression. In: New England Journal of Medicine. 2006 ; Vol. 354, No. 12. pp. 1243-1252.
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AU - Quitkin, Frederick

AU - Warden, Diane

AU - Ritz, Louise

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AU - Lebowitz, Barry D.

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N2 - 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).

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