title: Pre-treatment insomnia as a predictor of single and combination antidepressant outcomes: a CO-MED report.
abstract: BACKGROUND
  Most patients with major depressive disorder (MDD) report clinically significant sleep problems. Pre-treatment insomnia has been associated with poorer treatment outcomes in some antidepressant trials, leading to suggestions that combined treatment regimens may be more successful in this subgroup. This study investigated this question using data from the CO-MED trial.
  
  
  METHODS
  Adult outpatients with chronic and/or recurrent MDD were randomly assigned in 1:1:1 ratio to 28 weeks of single-blind, placebo-controlled antidepressant treatment with (1) escitalopram+placebo, (2) bupropion-sustained-release+escitalopram, or (3) venlafaxine-extended-release+mirtazapine. We compared baseline characteristics, tolerability, and treatment outcomes at 12 and 28 weeks for patients with and without pre-treatment insomnia.
  
  
  RESULTS
  Of the 665 evaluable patients, the majority (88.3%) reported significant pre-treatment insomnia. Those with pre-treatment insomnia were more likely to be female (69.3% vs. 57.7%) and African-American (29.1% vs. 11.8%). Those with pre-treatment insomnia symptoms reported higher rates of concurrent anxiety disorders, lower rates of alcohol and substance use disorders, and greater impairment in psychosocial functioning. The two groups did not differ in either tolerability or treatment outcomes among the three antidepressant treatments.
  
  
  CONCLUSIONS
  Insomnia symptoms, while common in patients with chronic/recurrent MDD were not predictive of response, remission, or tolerability with either single or combined antidepressant medications.
authors.affiliation: Office of Clinical Sciences, Duke-NUS Graduate Medical School Singapore, Singapore. Electronic address: sharon.sung@duke-nus.edu.sg.
authors.forename: Sharon C
authors.initials: SC
authors.lastname: Sung
authors.affiliation: Epidemiology Data Center, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Wisniewski
authors.affiliation: Epidemiology Data Center, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: James F
authors.initials: JF
authors.lastname: Luther
authors.affiliation: Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Madhukar H
authors.initials: MH
authors.lastname: Trivedi
authors.affiliation: Office of Clinical Sciences, Duke-NUS Graduate Medical School Singapore, Singapore.
authors.forename: A John
authors.initials: AJ
authors.lastname: Rush
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001008:Anxiety Disorders / Q000453:epidemiology; D016642:Bupropion / Q000627:therapeutic use; D015283:Citalopram / Q000627:therapeutic use; D015897:Comorbidity; D003511:Cyclohexanols / Q000627:therapeutic use; D003692:Delayed-Action Preparations; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000523:psychology*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives / Q000627:therapeutic use; D008875:Middle Aged; D000078785:Mirtazapine; D010045:Outpatients; D011237:Predictive Value of Tests; D016037:Single-Blind Method; D007319:Sleep Initiation and Maintenance Disorders / Q000175:diagnosis*; D019966:Substance-Related Disorders / Q000453:epidemiology; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D000069470:Venlafaxine Hydrochloride
chemical_list: D000928:Antidepressive Agents; D003511:Cyclohexanols; D003692:Delayed-Action Preparations; D016642:Bupropion; D015283:Citalopram; D008803:Mianserin; D000069470:Venlafaxine Hydrochloride; D000078785:Mirtazapine
keywords: Antidepressant; Insomnia; Major depressive disorder