Revisiting monoamine oxidase inhibitors for the treatment of depressive disorders: A systematic review and network meta-analysis

Background: Monoamine oxidase inhibitors (MAOIs) were the first class of modern antidepressants; however, they are under-utilized as compared to the newer antidepressants. Methods: In this systematic review, network meta-analysis was used to investigate the comparative efficacy and acceptability of MAOIs for depressive disorders. Overall, the network meta-analysis included 52 double-blind, randomized controlled trials (RCTs) that compared 14 antidepressants or placebo. Across studies, the mean arm size was n = 58 participants from a total N = 6462 (5309 active drug; 1153 placebo). Results: Except fluvoxamine, all antidepressants demonstrated superior efficacy to placebo, and none demonstrated substantially better or worse all-cause dropout rates. Phenelzine demonstrated superior evidence for efficacy compared to all other treatments, and clomipramine demonstrated superior evidence for acceptability compared to all other treatments. Limitations: The study is primarily limited by low estimate precision due to a relative paucity of studies for some of the included treatment conditions. Further evidence is required to study the relative efficacy of MAOIs against newer antidepressants. Conclusions: The results of this analysis largely support the re-evaluation of the use of MAOIs as antidepressant agents in the treatment algorithm of depression.