Tranylcypromine versus venlafaxine plus mirtazapine following three failed antidepressant medication trials for depression: a STAR*D report

Am J Psychiatry. 2006 Sep;163(9):1531-41; quiz 1666. doi: 10.1176/ajp.2006.163.9.1531.

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.

Method: Adult outpatients with nonpsychotic major depressive disorder who had not achieved remission or had withdrawn from treatment because of intolerance in three previous prospective medication trials were randomly assigned to receive open-label treatment with either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.

Publication types

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

MeSH terms

  • Adult
  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / therapeutic use*
  • Antidepressive Agents, Second-Generation / therapeutic use
  • Antidepressive Agents, Tricyclic / therapeutic use
  • Cyclohexanols / therapeutic use*
  • Delayed-Action Preparations
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / psychology
  • Drug Administration Schedule
  • Drug Resistance
  • Drug Therapy, Combination
  • Female
  • Humans
  • Interviews as Topic
  • Male
  • Mianserin / analogs & derivatives*
  • Mianserin / therapeutic use
  • Middle Aged
  • Mirtazapine
  • Psychiatric Status Rating Scales / statistics & numerical data
  • Tranylcypromine / adverse effects
  • Tranylcypromine / therapeutic use*
  • Treatment Outcome
  • Venlafaxine Hydrochloride

Substances

  • Antidepressive Agents
  • Antidepressive Agents, Second-Generation
  • Antidepressive Agents, Tricyclic
  • Cyclohexanols
  • Delayed-Action Preparations
  • Mianserin
  • Tranylcypromine
  • Venlafaxine Hydrochloride
  • Mirtazapine