Combining Medications to Enhance Depression Outcomes (CO-MED)

Acute and long-term outcomes of a single-blind randomized study

A. John Rush, Madhukar H. Trivedi, Jonathan W. Stewart, Andrew A. Nierenberg, Maurizio Fava, Benji T. Kurian, Diane Warden, David W. Morris, James F. Luther, Mustafa M. Husain, Ian A. Cook, Richard C. Shelton, Ira M. Lesser, Susan G. Kornstein, Stephen R. Wisniewski

Research output: Contribution to journalArticle

206 Citations (Scopus)

Abstract

Objective: Two antidepressant medication combinations were compared with selective serotonin reuptake inhibitor monotherapy to determine whether either combination produced a higher remission rate in first-step acute-phase (12 weeks) and long-term (7 months) treatment. Method: The single-blind, prospective, randomized trial enrolled 665 outpatients at six primary and nine psychiatric care sites. Participants had at least moderately severe nonpsychotic chronic and/or recurrent major depressive disorder. Escitalopram (up to 20 mg/day) plus placebo, sustained-release bupropion (up to 400 mg/day) plus escitalopram (up to 20 mg/day), or extended-release venlafaxine (up to 300 mg/day) plus mirtazapine (up to 45 mg/day) was delivered (1:1:1 ratio) by using measurement-based care. The primary outcome was remission, defined as ratings of less than 8 and less than 6 on the last two consecutive applications of the 16-item Quick Inventory of Depressive Symptomatology - Self-Report. Secondary outcomes included side effect burden, adverse events, quality of life, functioning, and attrition. Results: Remission and response rates and most secondary outcomes were not different among treatment groups at 12 weeks. The remission rates were 38.8% for escitalopram-placebo, 38.9% for bupropion-escitalopram, and 37.7% for venlafaxine-mirtazapine, and the response rates were 51.6%-52.4%. The mean number of worsening adverse events was higher for venlafaxine-mirtazapine (5.7) than for escitalopram-placebo (4.7). At 7 months, remission rates (41.8%-46.6%), response rates (57.4%-59.4%), and most secondary outcomes were not significantly different. Conclusions: Neither medication combination outperformed monotherapy. The combination of extended-release venlafaxine plus mirtazapine may have a greater risk of adverse events.

Original languageEnglish (US)
Pages (from-to)689-701
Number of pages13
JournalAmerican Journal of Psychiatry
Volume168
Issue number7
DOIs
StatePublished - Jul 2011

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Single-Blind Method
Citalopram
Depression
Bupropion
Placebos
Major Depressive Disorder
Serotonin Uptake Inhibitors
Self Report
Antidepressive Agents
Psychiatry
Outpatients
Quality of Life
Equipment and Supplies
mirtazapine
Venlafaxine Hydrochloride
Therapeutics

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Combining Medications to Enhance Depression Outcomes (CO-MED) : Acute and long-term outcomes of a single-blind randomized study. / Rush, A. John; Trivedi, Madhukar H.; Stewart, Jonathan W.; Nierenberg, Andrew A.; Fava, Maurizio; Kurian, Benji T.; Warden, Diane; Morris, David W.; Luther, James F.; Husain, Mustafa M.; Cook, Ian A.; Shelton, Richard C.; Lesser, Ira M.; Kornstein, Susan G.; Wisniewski, Stephen R.

In: American Journal of Psychiatry, Vol. 168, No. 7, 07.2011, p. 689-701.

Research output: Contribution to journalArticle

Rush, AJ, Trivedi, MH, Stewart, JW, Nierenberg, AA, Fava, M, Kurian, BT, Warden, D, Morris, DW, Luther, JF, Husain, MM, Cook, IA, Shelton, RC, Lesser, IM, Kornstein, SG & Wisniewski, SR 2011, 'Combining Medications to Enhance Depression Outcomes (CO-MED): Acute and long-term outcomes of a single-blind randomized study', American Journal of Psychiatry, vol. 168, no. 7, pp. 689-701. https://doi.org/10.1176/appi.ajp.2011.10111645
Rush, A. John ; Trivedi, Madhukar H. ; Stewart, Jonathan W. ; Nierenberg, Andrew A. ; Fava, Maurizio ; Kurian, Benji T. ; Warden, Diane ; Morris, David W. ; Luther, James F. ; Husain, Mustafa M. ; Cook, Ian A. ; Shelton, Richard C. ; Lesser, Ira M. ; Kornstein, Susan G. ; Wisniewski, Stephen R. / Combining Medications to Enhance Depression Outcomes (CO-MED) : Acute and long-term outcomes of a single-blind randomized study. In: American Journal of Psychiatry. 2011 ; Vol. 168, No. 7. pp. 689-701.
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AU - Trivedi, Madhukar H.

AU - Stewart, Jonathan W.

AU - Nierenberg, Andrew A.

AU - Fava, Maurizio

AU - Kurian, Benji T.

AU - Warden, Diane

AU - Morris, David W.

AU - Luther, James F.

AU - Husain, Mustafa M.

AU - Cook, Ian A.

AU - Shelton, Richard C.

AU - Lesser, Ira M.

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N2 - Objective: Two antidepressant medication combinations were compared with selective serotonin reuptake inhibitor monotherapy to determine whether either combination produced a higher remission rate in first-step acute-phase (12 weeks) and long-term (7 months) treatment. Method: The single-blind, prospective, randomized trial enrolled 665 outpatients at six primary and nine psychiatric care sites. Participants had at least moderately severe nonpsychotic chronic and/or recurrent major depressive disorder. Escitalopram (up to 20 mg/day) plus placebo, sustained-release bupropion (up to 400 mg/day) plus escitalopram (up to 20 mg/day), or extended-release venlafaxine (up to 300 mg/day) plus mirtazapine (up to 45 mg/day) was delivered (1:1:1 ratio) by using measurement-based care. The primary outcome was remission, defined as ratings of less than 8 and less than 6 on the last two consecutive applications of the 16-item Quick Inventory of Depressive Symptomatology - Self-Report. Secondary outcomes included side effect burden, adverse events, quality of life, functioning, and attrition. Results: Remission and response rates and most secondary outcomes were not different among treatment groups at 12 weeks. The remission rates were 38.8% for escitalopram-placebo, 38.9% for bupropion-escitalopram, and 37.7% for venlafaxine-mirtazapine, and the response rates were 51.6%-52.4%. The mean number of worsening adverse events was higher for venlafaxine-mirtazapine (5.7) than for escitalopram-placebo (4.7). At 7 months, remission rates (41.8%-46.6%), response rates (57.4%-59.4%), and most secondary outcomes were not significantly different. Conclusions: Neither medication combination outperformed monotherapy. The combination of extended-release venlafaxine plus mirtazapine may have a greater risk of adverse events.

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