IntroductionClinicians treating patients with Major Depressive Disorder (MDD) might favor one second-generation antidepressant (SGA) because of perceived benefits for the accompanying symptoms of MDD.ObjectivesTo compare the efficacy of bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, sertraline, trazodone, and venlafaxine for the treatment of the accompanying symptoms of MDD.MethodsThis review is part of a larger review on the comparative effectiveness of SGAs for MDD. We searched MEDLINE, Embase, The Cochrane Library, and the International Pharmaceutical Abstracts up to May 2010. Two persons independently reviewed the literature, abstracted data, and rated the risk of bias.ResultsWe located 26 head-to-head and 7 placebo-controlled trials that provided evidence for this review. We did not locate any studies on treating accompanying appetite change, low energy, melancholia, or psychomotor change. There was no evidence for many comparisons and we were unable to conduct quantitative analysis for any comparisons. For the comparisons that were studied, we concluded that the SGAs are similarly efficacious for treating anxiety, insomnia, pain, and somatization. The strength of the evidence for these conclusions is low (meaning further research is very likely to have an important impact on our confidence in the estimate of the effect and is likely to change the estimate).ConclusionsOur findings indicate that the existing evidence does not warrant the choice of one second-generation antidepressant over another based on greater efficacy for the accompanying symptoms of depression.