Antidepressant combos compared to monotherapy for acute depression

Combinations of antidepressants are associated with superior treatment outcomes compared with monotherapy for adults with acute depression, according to a review published online Feb. 16 in JAMA Psychiatry.

Jonathan Henssler, M.D., from the University of Cologne in Germany, and colleagues conducted a systematic literature review to identify randomized clinical trials (RCTs) comparing combinations of antidepressants with antidepressant monotherapy in adult patients with acute depression.

In a meta-analysis based on data from 39 RCTs (6,751 patients), the researchers found that combination treatment was statistically significantly associated with superior treatment outcomes versus monotherapy (standardized mean difference [SMD], 0.31). The combination of a reuptake inhibitor and an antagonist of presynaptic α2-autoreceptors was superior to other combinations (SMD, 0.37). Combinations with bupropion were not superior to monotherapy (SMD, 0.10). All treatments had similar numbers of dropouts and dropouts due to adverse events. Results remained robust across prespecified secondary outcomes and sensitivity and subgroup analyses, including analyses restricted to studies with a low risk for bias, despite study heterogeneity and an indication of publication bias.

"Combination therapy using an antagonist of presynaptic α2-autoreceptors may be an effective and safe antidepressant treatment option for patients who are nonresponders to monotherapy and as a potential first-line treatment in severe cases of depression," the authors write.

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