People with particular medical illnesses are at an increased risk of depression. Similarly, other psychiatric or behavioral illnesses increase the risk of depressive disorders. there is a growing interest in the comparative benefits and harms of second-generation antidepressants for treating depression with co-occurring illness.

To compare the benefits and harms of bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, sertraline, trazodone, and venlafaxine for the treatment of depressive syndromes in certain demographic populations (e.g., older adults) and in subgroups with comorbidities.

We updated a comparative effectiveness review (CER) published in 2007 by the Agency for Healthcare Research and Quality searching 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. in addition, investigators graded the strength of the body of evidence.

Evidence on subgroups is sparse. Head-to-head RCTs often exclude subgroups. We found no studies designed to compare a particular subgroup with the general population. in older adults, efficacy does not differ substantially among second-generation antidepressants; however, there may be some differences in adverse events. We found no head-to-head trials comparing efficacy and harms in different race or ethnic groups. Comparative evidence on comorbidities was limited to a subgroup analysis of depressed adults with generalized anxiety disorder.

There is a great need for research focusing directly on the efficacy and safety of second-generation antidepressants in these more vulnerable populations.