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

Abstract

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.

Keywords::

• antidepressant
• combination
• evidence
• guideline
• major depressive disorder
• monotherapy

Financial & competing interests disclosure

This study was supported by a grant of the Korean Healthcare technology R & D Project, Ministry of Health and Welfare, Republic of Korea (A102065). Research funding within the last 5 years has been received from GlaxoSmithKline Korea, GlaxoSmithKline USA, AstraZeneca Korea, Janssen Pharmaceuticals Korea, McNeil Consumer and Specialty Inc., Forest Lab, Johnson and Johnson, Inc., Eli Lilly and Company Korea, Korean Research Foundation, Korea Otsuka Pharmaceuticals, Inc., Wyeth Korea, Korean Institute of Science and Technology Evaluation and Planning, Korea Science and Engineering Foundation, and Sanofi-Aventis Korea.

Honorarium for consultancy or speaking within the last 5 years has been received from GlaxoSmithKline Korea, Lundbeck Korea, Wyeth Korea, AstraZeneca Korea, Janssen Pharmaceuticals Korea, Norvatis Korea, Jeil Pharmaceuticals, Hanlim Pharmaceuticals, WhanIn Pharmaceuticals, Inc., Bugwang Pharmaceuticals, Pfizer Korea, Eli Lilly and Company Korea, Korea Otsuka Pharmaceuticals, Inc., Sandoz Korea, Sanofi-Aventis Korea, RH Korea, Eisai Korea, and Korea Institute of Science and Technology. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.