Combining medications to enhance depression outcomes (CO-MED): acute and long-term outcomes of a single-blind randomized study

Am J Psychiatry. 2011 Jul;168(7):689-701. doi: 10.1176/appi.ajp.2011.10111645. Epub 2011 May 2.

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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antidepressive Agents / therapeutic use*
  • Bupropion / therapeutic use
  • Citalopram / therapeutic use
  • Cyclohexanols / therapeutic use
  • Depressive Disorder, Major / diagnosis
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / psychology
  • Drug Therapy, Combination
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Personality Inventory
  • Recurrence
  • Self Report
  • Serotonin Uptake Inhibitors / therapeutic use
  • Single-Blind Method
  • Treatment Outcome
  • Venlafaxine Hydrochloride

Substances

  • Antidepressive Agents
  • Cyclohexanols
  • Serotonin Uptake Inhibitors
  • Bupropion
  • Citalopram
  • Venlafaxine Hydrochloride