title: Combining medications to enhance depression outcomes (CO-MED): acute and long-term outcomes of a single-blind randomized study.
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.
  
  
  METHODS
  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.
authors.affiliation: Duke–National University of Singapore Graduate Medical School, Singapore.
authors.forename: A John
authors.initials: AJ
authors.lastname: Rush
authors.forename: Madhukar H
authors.initials: MH
authors.lastname: Trivedi
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Stewart
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Nierenberg
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fava
authors.forename: Benji T
authors.initials: BT
authors.lastname: Kurian
authors.forename: Diane
authors.initials: D
authors.lastname: Warden
authors.forename: David W
authors.initials: DW
authors.lastname: Morris
authors.forename: James F
authors.initials: JF
authors.lastname: Luther
authors.forename: Mustafa M
authors.initials: MM
authors.lastname: Husain
authors.forename: Ian A
authors.initials: IA
authors.lastname: Cook
authors.forename: Richard C
authors.initials: RC
authors.lastname: Shelton
authors.forename: Ira M
authors.initials: IM
authors.lastname: Lesser
authors.forename: Susan G
authors.initials: SG
authors.lastname: Kornstein
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Wisniewski
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use*; D016642:Bupropion / Q000627:therapeutic use; D015283:Citalopram / Q000627:therapeutic use; D003511:Cyclohexanols / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010555:Personality Inventory; D012008:Recurrence; D057566:Self Report; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D016037:Single-Blind Method; D016896:Treatment Outcome; D000069470:Venlafaxine Hydrochloride
chemical_list: D000928:Antidepressive Agents; D016642:Bupropion; D015283:Citalopram; D003511:Cyclohexanols; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride