title: Adherence to antidepressant combinations and monotherapy for major depressive disorder: a CO-MED report of measurement-based care.
abstract: BACKGROUND
  Non-adherence to antidepressant treatment is not routinely measured in practical clinical trials. It has not been related to outcomes in a large sample of adults with chronic and/or recurrent major depressive disorder (MDD) or any sample treated with antidepressant combinations.
  
  
  METHODS
  Adult outpatients with chronic and/or recurrent MDD were randomized to 12 weeks of treatment with bupropion-SR plus escitalopram, venlafaxine-XR plus mirtazapine, or escitalopram plus placebo. We compared non-adherence (the frequency with which daily medications were not taken) and specifically the frequency of temporarily stopping and/or skipping medication, or reducing or increasing the dose across treatments in 567 participants using a self-report questionnaire collected at each visit. We tested the association between non-adherence, and both treatment type and outcomes.
  
  
  RESULTS
  A non-adherence rate under 10% was reported by 77.9%, 70.9%, and 71.6% of participants during weeks 1-4, 5-12, and 1-12, respectively. Antidepressant combinations were associated with a higher non-adherence rate than monotherapy during weeks 1-4 and 1-12. During weeks 1-4, 24.1% stopped/skipped doses and 6.1% reduced the dose. During weeks 5-12, 34.7% stopped/skipped doses and 9.4% reduced the dose. Across 12 weeks, 43.2% stopped/skipped doses, and 12.9% reduced the dose. Stopping/skipping doses during all time frames and dose decreases during weeks 1-12 occurred most frequently with combination treatments. Non-adherence was unrelated to symptom remission, response, or symptom change.
  
  
  CONCLUSIONS
  With closely monitored treatment, non-adherence is low and unrelated to depressive symptom outcome. Nonadherence is highest with antidepressant combinations. Specific non-adherent events are most often sporadic.
authors.affiliation: WARDEN, TRIVEDI, CARMODY, TOUPS, MYERS, RING, KURIAN, and MORRIS: University of Texas Southwestern Medical Center at Dallas; ZISOOK: University of California San Diego and San Diego VA Healthcare System; LESSER: Harbor- UCLA Medical Center, Torrance, CA; RUSH: Duke-National University of Singapore Graduate Medical School, Singapore.
authors.forename: Diane
authors.initials: D
authors.lastname: Warden
authors.forename: Madhukar H
authors.initials: MH
authors.lastname: Trivedi
authors.forename: Thomas
authors.initials: T
authors.lastname: Carmody
authors.forename: Marisa
authors.initials: M
authors.lastname: Toups
authors.forename: Sidney
authors.initials: S
authors.lastname: Zisook
authors.forename: Ira
authors.initials: I
authors.lastname: Lesser
authors.forename: Alyson
authors.initials: A
authors.lastname: Myers
authors.forename: Kolette Ring Benji
authors.initials: KR
authors.lastname: Kurian
authors.forename: David
authors.initials: D
authors.lastname: Morris
authors.forename: A John
authors.initials: AJ
authors.lastname: Rush
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016642:Bupropion / Q000008:administration & dosage / Q000627:therapeutic use*; D002908:Chronic Disease; D015283:Citalopram / Q000627:therapeutic use*; D003511:Cyclohexanols / Q000008:administration & dosage / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004359:Drug Therapy, Combination / Q000706:statistics & numerical data*; D005260:Female; D006801:Humans; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008875:Middle Aged; D000078785:Mirtazapine; D010919:Placebos; D012008:Recurrence; D016896:Treatment Outcome; D000069470:Venlafaxine Hydrochloride; D016903:Drug Monitoring
chemical_list: D000928:Antidepressive Agents; D003511:Cyclohexanols; D010919:Placebos; D016642:Bupropion; D015283:Citalopram; D008803:Mianserin; D000069470:Venlafaxine Hydrochloride; D000078785:Mirtazapine