ACP guideline: New antidepressants are similarly effective

Clinical question Of the new (noncyclic) antidepressants, which one should be used first in patients with major depressive disorder?

Bottom line Citing similar effectiveness and effect on quality of life, this guideline from the American College of Physicians (ACP) recommends choosing a second-generation antidepressant on the basis of factors other than effectiveness. They suggest selecting an antidepressant according to its side effect profile, cost, and patient preference; not by mechanism of action or presumed differences in effectiveness. Mirtazapine (Remeron) has been found to have a faster onset in the first 2 weeks, but this difference disappears by the fourth week. The guidelines also point out that a significant number—almost half— of patients will not respond to the first antidepressant selected and that only 1 in 4 who are switched to a second antidepressant will respond. (Level of evidence = 1a)

Synopsis To develop this guideline, the ACP commissioned a systematic review of the literature comparing the newer antidepressants, such as the selective serotonin reuptake inhibitors, norepinephrine reuptake inhibitors, and selective serotonin norepinephrine reuptake inhibitors. Searching five databases, including the Cochrane Registry, the authors identified 80 English language head-to-head randomized controlled trials enrolling more than 17,000 patients. Studies were independently selected by two researchers, conducting meta-analyses when the data could be combined. The group found moderate evidence supporting equivalence among the second-generation antidepressants with regard to comparative efficacy, effectiveness, quality of life, and maintaining response. Mirtazapine has a faster onset of action, producing a significantly better response after 2 weeks of treatment, though the difference disappears by week 4. Anxiety responds well to any antidepressant. The authors did not locate research allowing them to conclude whether any antidepressant is better than any other at controlling melancholia, pain, or insomnia. Venlafaxine (Effexor) is more likely to cause nausea, sertraline (Zoloft) causes more diarrhea, and mirtazapine is associated with weight gain. Bupropion is less likely to cause sexual dysfunction.

Qaseem A, Snow V, Denberg TD, et al; Clinical Efficacy Assessment Subcommittee of American College of Physicians. Using second-generation antidepressants to treat depressive disorders: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2008;149(10):725-733.