Do we need more than one antidepressant for patients with major depressive disorder?

Evaluation of: Rush AJ, Trivedi MH, Stewart JW et al. Combining medications to enhance depression outcomes (CO-MED): acute and long-term outcomes of a single-blind randomized study. Am. J. Psychiatry 168(7), 689-701 (2011). According to currently existing treatment guidelines, when a single antidepressant medication is not working, the common next step treatment is to switch to another class of antidepressants or to add another one to the first therapeutic agent. With regard to this issue, combination therapy has been suggested to provide unexpected synergy for patients, resulting in more remission compared with switching strategies, although some debates are still ongoing. Recently, Rush and colleagues have investigated whether two antidepressant combination treatments should produce a higher remission rate in first-step acute-phase (12 weeks) and long-term (7 months) treatment compared with monotherpay. They failed to find any superiority of combination treatment over monotherapy in terms of efficacy and safety. The remission and response rates and most secondary outcomes were not different among treatment groups at 12 weeks and 7 months, while the mean number of worsening adverse events was higher for combination treatment (5.7) than for monotherapy (4.7) at 12 weeks. This article will discuss the clinical and further research implications in the context of the potential limitations and significance of this recent study.