Tranylcypromine versus tricyclic antidepressants for depression: A comprehensive meta-analysis

Introduction:

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

Methods:

Literature was searched for trials of TCP controlled by TCA in multiple databases and in reviews of tranylcypromine 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 non-responders.

Results:

227 trials of TCP have been found including 75 controlled trials of TCP-monotherapy. 12 of 23 trials of TCP-monotherapy and TCA have been excluded for several reasons (duplicates, safety studies, retrospective, cross-over) leaving 11 controlled prospective and parallel trials of TCP-monotherapy versus TCA (six randomized double-blind). One study was excluded from the meta-analysis because of high risk of bias according to the Cochrane's tool. Two studies with equal efficacy of TCP and TCA in continuous endpoints did not provide dichotomous data. A pooled logOR = 0.480 (95%CI 0.105 – 0.857, p = 0.012) resulted for the remaining eight studies, which favors TCP significantly over TCA (test for heterogeneity: Χ2 = 8.1, df = 7, p > 0.3, not heterogenous; I2 = 13.6%, heterogeneity not important). The result is robust with respect to inclusion of hypothetical data of the two studies with continuous data only: pooled logOR = 0.350 (95%CI 0.028 – 0.672, p = 0.033). Visual inspection of Forest-plots and subgroup analysis suggest that superiority of TCP over TCA is determined by two trials in psychomotor retarded depression. Patients with predominantly severe agitated depression were not investigated in the studies of TCP-monotherapy. TCP was superior to TCA in terms of significantly lower frequencies of anticholinergic adverse effects (dry mouth, constipation, blurred vision, confusion) and tremor. In contrast, TCA had a lower frequency of insomnia.

Conclusion:

It is concluded that TCP and TCA have an equal antidepressant effect in a mean sample of patients with depression and that TCP might be superior to TCA in depression with psychomotor retardation.