Efficacy and Adverse Effects of Tranylcypromine and Tricyclic Antidepressants in the Treatment of Depression: A Systematic Review and Comprehensive Meta-analysis

J Clin Psychopharmacol. Jan/Feb 2020;40(1):63-74. doi: 10.1097/JCP.0000000000001153.


Purpose: We conducted a comprehensive meta-analysis of the comparison of tranylcypromine (TCP) and tricyclic antidepressants (TCAs) in the treatment of depression because such work is lacking in medical scientific literature.

Methods: Literature was searched for studies of TCP controlled by TCAs in multiple databases and in reviews of TCP and monoamine oxidase inhibitors. The natural logarithm of the odds ratio (logOR) and the pooled logOR according to a fixed effect model were calculated for the numbers of responders and nonresponders.

Results: A total of 227 studies of TCP were found including 75 controlled studies of TCP-monotherapy. Twelve of 23 studies of TCP monotherapy and TCAs were excluded for several reasons (duplicates, safety studies, retrospective, cross-over), leaving 11 prospective and parallel controlled studies of TCP monotherapy versus TCAs (6 randomized double-blind). One study was excluded from the meta-analysis because of low quality of study design according to the Food and Drug Administration guidelines of studies of antidepressant drugs and high risk of bias according to the Cochrane's tool. Two studies with equal efficacy of TCP and TCAs in continuous endpoints did not provide dichotomous response data. A pooled logOR of 0.480 (95% confidence interval, 0.105-0.857, P = 0.01) resulted for the remaining eight studies in the primary meta-analysis, which favors TCP significantly over TCAs (test for heterogeneity: Х = 8.1, df = 7, P > 0.3, not heterogenous; I = 13.6%, heterogeneity not important). The result is robust with respect to inclusion of hypothetical response data of the 2 studies with continuous data only: pooled logOR, 0.350 (95% confidence interval, 0.028-0.672, P = 0.03). Visual inspection of forest plots and subgroup analysis suggest that superiority of TCP over TCAs is determined by 2 studies in psychomotor-retarded (anergic) depression.

Conclusions: Tranylcypromine and TCAs have an equal antidepressant effect in a mean sample of depressed patients with mixed psychomotor symptoms. Tranylcypromine might be superior to TCAs in depression with predominant psychomotor retardation.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Adult
  • Affect / drug effects*
  • Aged
  • Antidepressive Agents, Tricyclic / adverse effects
  • Antidepressive Agents, Tricyclic / therapeutic use*
  • Depression / diagnosis
  • Depression / drug therapy*
  • Depression / psychology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Monoamine Oxidase Inhibitors / adverse effects
  • Monoamine Oxidase Inhibitors / therapeutic use*
  • Psychomotor Performance / drug effects
  • Tranylcypromine / adverse effects
  • Tranylcypromine / therapeutic use*
  • Treatment Outcome
  • Young Adult


  • Antidepressive Agents, Tricyclic
  • Monoamine Oxidase Inhibitors
  • Tranylcypromine