title: Tranylcypromine versus venlafaxine plus mirtazapine following three failed antidepressant medication trials for depression: a STAR*D report.
abstract: OBJECTIVE
  The purpose of this study was to compare the effectiveness and tolerability of tranylcypromine and combination treatment with extended-release venlafaxine and mirtazapine in patients with treatment-resistant major depression whose current depressive episode had not responded adequately to treatment in three prior prospective medication trials.
  
  
  METHODS
  Adult outpatients with nonpsychotic major depressive disorder who had not achieved remission or had withdrawn from treatment because of intolerance in three previous prospective medication trials were randomly assigned to receive open-label treatment with either tranylcypromine (N=58) or extended-release venlafaxine plus mirtazapine (N=51). The primary outcome measure was whether patients achieved remission, which was defined as a score < or =7 at exit on the 17-item Hamilton Depression Rating Scale (HAM-D). The HAM-D was administered by telephone by raters to whom treatment was masked.
  
  
  RESULTS
  Remission rates were not significantly different between the two treatment groups (6.9% for the tranylcypromine group and 13.7% for the venlafaxine plus mirtazapine group). The mean daily dose at exit for tranylcypromine was 36.9 mg (SD=18.5); for venlafaxine, 210.3 mg (SD=95.2); and for mirtazapine, 35.7 mg (SD=17.6). Tranylcypromine was associated with significantly less symptom reduction and greater attrition due to intolerance.
  
  
  CONCLUSIONS
  Remission rates were modest for both the tranylcypromine group and the extended-release venlafaxine plus mirtazapine group, and the rates were not statistically different between groups. The lower side effect burden, lack of dietary restrictions, and ease of use of venlafaxine and mirtazapine suggest that this combination may be preferred over tranylcypromine for patients with highly treatment-resistant depression who have not benefited adequately from several prior treatments.
authors.affiliation: Depression Evaluation Service, New York State Psychiatric Institute, 1051 Riverside Dr., New York, NY 10032, USA. mcgrath@pi.cpmc.columbia.edu
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: McGrath
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Stewart
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fava
authors.forename: Madhukar H
authors.initials: MH
authors.lastname: Trivedi
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Wisniewski
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Nierenberg
authors.forename: Michael E
authors.initials: ME
authors.lastname: Thase
authors.forename: Lori
authors.initials: L
authors.lastname: Davis
authors.forename: Melanie M
authors.initials: MM
authors.lastname: Biggs
authors.forename: Kathy
authors.initials: K
authors.lastname: Shores-Wilson
authors.forename: James F
authors.initials: JF
authors.lastname: Luther
authors.forename: George
authors.initials: G
authors.lastname: Niederehe
authors.forename: Diane
authors.initials: D
authors.lastname: Warden
authors.forename: A John
authors.initials: AJ
authors.lastname: Rush
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use; D003511:Cyclohexanols / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D004334:Drug Administration Schedule; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007407:Interviews as Topic; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008875:Middle Aged; D000078785:Mirtazapine; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D014191:Tranylcypromine / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D000069470:Venlafaxine Hydrochloride
chemical_list: D000928:Antidepressive Agents; D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D003511:Cyclohexanols; D003692:Delayed-Action Preparations; D008803:Mianserin; D014191:Tranylcypromine; D000069470:Venlafaxine Hydrochloride; D000078785:Mirtazapine