Relative effectiveness of tricyclic antidepressant versus monoamine oxidase inhibitor monotherapy for treatment-resistant depression

Abstract Objectives Antidepressants may be less effective in treatment-resistant depression (TRD). In this exploratory study, we examined the widely held hypothesis that monoamine oxidase inhibitor (MAOI) therapy may be superior to tricyclic antidepressant (TCA) therapy for TRD. We also examined the influence of the number of prior treatment trials on TCA versus MAOI effectiveness in TRD. Methods Data were retrospectively extracted from approximately 2,500 treatment charts of patients with TRD who were attending a university mood disorder clinic between 1983 and 2015. Hierarchical linear modeling was used to examine the efficacy of drug class on outcome as well as the interaction between drug class and the number of prior antidepressant trials. Results 147 treatment outcome observations were made from 94 unipolar, depressed patients who either received TCA ( N  = 47) or MAOI ( N  = 100) monotherapy for TRD. For patients unresponsive to at least one prior trial, drug class significantly predicted end-of-treatment CGI/S scores, with TCAs showing worse (i.e., higher) end-of-treatment CGI/S scores relative to MAOI therapy ( b  = 1.04, t  = 4.98, p b  = −0.50, t  = −2.43, p  = 0.02); however, the advantage for MAOI versus TCA therapy decreases with more prior, failed, antidepressant trials. Conclusion Results suggest that MAOIs may be more effective than TCAs for early stage TRD. This difference in effectiveness between MAOIs and TCAs diminished as the number of prior treatment trials increased. However, the TCA sample size was limited and the analysis was retrospective with non-randomized conditions.