A review of published evidence of superior efficacy of a particular antidepressant in major depressive disorder may assist clinicians in making considered treatment choices. To identify such candidates, an international group of experts met to assess published evidence (identified through searches in Medline and Embase databases and discussions with experts in the field) from randomized, controlled trials and meta-analyses comparing two antidepressants under conditions of fair comparison. Criteria were defined to judge the strength of evidence. Two pivotal studies in moderate-to-severe major depressive disorder that demonstrate superiority on the primary efficacy measure, or alternatively one pivotal study supported by consistent results from meta-analyses, was considered to constitute evidence for definite superiority. Three antidepressants met these criteria: clomipramine, venlafaxine, and escitalopram. Three antidepressants were found to have probable superiority: milnacipran, duloxetine, and mirtazapine. Only escitalopram was found to have definite superiority in the treatment of severe depression; probable superiority was identified for venlafaxine and possible superiority for milnacipran and clomipramine. This review of published data found evidence that only a very few antidepressants are shown to be more effective than others.