MAOIs Better Than Tricyclic Antidepressants for Early Stage Treatment-Resistant Depression

The use of monoamine oxidase inhibitors (MAOIs) could be more effective than tricyclic antidepressants (TCAs) for patients with treatment-resistant depression, according to study results published in the Journal of Affective Disorders.

Researchers retrospectively reviewed data of 147 patients with unipolar major depressive disorder who were treated with a single-agent MAOI (n=100) or TCA (n=47). Data was collected from the Depression Research Unit at the University of Pennsylvania Medical Center in Philadelphia from 1983 to 2015. The primary outcome measured was the end-of-therapy Clinical Global Impressions/Severity Scale score. Linear modeling was used to examine associations between antidepressant efficacy and clinical outcomes.

After analysis, the team reported that participants who were unresponsive to a minimum of 1 prior antidepressant trial, MAOIs showed better end-of-therapy Clinical Global Impressions/Severity Scale scores relative to TCAs (regression coefficient, 1.04; t-statistic, 4.98; P <.0001). However, the researchers found that the benefit seen with MAOI therapy was reduced as the number of unsuccessful antidepressant trials increased.

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Key study limitations included the retrospective design and small sample size. In addition, the current study did not compare TCA or MAOI outcomes to those of other antidepressant drug classes. “[MAOIs] appear to be efficacious for subjects with early stage [treatment-resistant depression] compared to TCAs; however, this advantage seems to decrease with an increase in number of prior antidepressant trials. Future research should attempt to replicate this phenomenon and examine, with a larger sample, whether TCA therapy exhibits a similar decrease in effectiveness as MAOI therapy,” the researchers concluded.


Kim T, Xu C, Amsterdam JD. Relative effectiveness of tricyclic antidepressant versus monoamine oxidase inhibitor monotherapy for treatment-resistant depression. J Affect Disord. 2019;250:199-203.