Direct comparison of tricyclic and serotonin-reuptake inhibitor antidepressants in randomized head-to-head trials in acute major depression: Systematic review and meta-analysis

Abstract

Background:

A comparison across trials conducted over several decades suggested superior efficacy of tricyclic antidepressants (TCAs) over selective serotonin-reuptake inhibitors (SSRIs). However, this outcome may reflect a selective secular decline of responses after randomization to placebo. Remaining uncertainty encouraged direct comparison of the drug-types in trials involving randomized, head-to-head comparisons.

Methods:

We systematically identified reports of randomized trials of TCAs versus SSRIs for major depression in several digital databases, and applied standard meta-analytic and multiple-factor regression methods to analyze and pool the findings.

Results:

In 89 head-to-head trials, there was no detectable overall difference in responder rates or percent-improvement between TCAs and SSRIs. In addition to non-difference between drug-types, outcomes were unrelated to reporting-year, trial-size or nominal duration, proportion of women participants, initial depression ratings, rating scales, subjects/arm, imipramine-equivalent mg/day drug dose, or dropout rate. Trial size and duration increased significantly over the years 1980–2016.

Conclusions:

Previous evidence suggesting superior benefits of TCAs over SSRIs for the treatment of acute major depression is probably an artifact of a selective secular decline in responses to placebo, as no difference was found in a large series of direct comparisons of these antidepressant-types.