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Title: Combining Medications to Enhance Depression Outcomes (CO-MED): Acute and long-term outcomes of a single-blind randomized study
Authors: Rush, A.J. 
Trivedi, M.H.
Stewart, J.W.
Nierenberg, A.A.
Fava, M.
Kurian, B.T.
Warden, D.
Morris, D.W.
Luther, J.F.
Husain, M.M.
Cook, I.A.
Shelton, R.C.
Lesser, I.M.
Kornstein, S.G.
Wisniewski, S.R.
Issue Date: Jul-2011
Citation: Rush, A.J., Trivedi, M.H., Stewart, J.W., Nierenberg, A.A., Fava, M., Kurian, B.T., Warden, D., Morris, D.W., Luther, J.F., Husain, M.M., Cook, I.A., Shelton, R.C., Lesser, I.M., Kornstein, S.G., Wisniewski, S.R. (2011-07). Combining Medications to Enhance Depression Outcomes (CO-MED): Acute and long-term outcomes of a single-blind randomized study. American Journal of Psychiatry 168 (7) : 689-701. ScholarBank@NUS Repository.
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.
Source Title: American Journal of Psychiatry
ISSN: 0002953X
DOI: 10.1176/appi.ajp.2011.10111645
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