The Year in Psychiatry: Studies Not to Miss From 2011

Christoph U. Correll, MD; Maren Carbon, MD


November 23, 2011

In This Article

Are 2 Antidepressants Better Than 1?

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. 2011;168:689-701.

This is a negative trial at first glance, but nonetheless it is an important study. The authors set out to systematically test a strategy that is frequently employed in clinical practice but without a clear empirical evidence base. They tested combinations of antidepressants vs monotherapy for the acute treatment (12 weeks) as well as r the long-term treatment (7 months) of unipolar depression. Compared were escitalopram (up to 20 mg/day) plus placebo, sustained-release bupropion (up to 400 mg/day) plus escitalopram (up to 20 mg/day), or extended-release venlafaxine (up to 300 mg/day) plus mirtazapine (up to 45 mg/day). The study was single-blind; self-reported measures of depression were chosen as the primary outcome, and rather broad inclusion criteria ensured approximating a real-world setting. Patients knew what baseline antidepressant they were taking but remained blind regarding the add-on treatment. Of note, the combination of 2 antidepressants was not superior compared with antidepressant monotherapy. On the contrary, a higher rate of adverse events occurred in the venlafaxine-mirtazapine combination group. Remission and response rates did not differ at 12 weeks or at 7 months. All treatments showed comparable effects on quality of life, work, and social adjustment.

Although the tested combinations may not be representative for all possible combinations of antidepressants, and although patients consenting to a randomized, controlled, single-blind study may not be as severely ill as patients unable or unwilling to consent to such a trial, it is likely that these results can be generalized to more combinations and many patients receiving antidepressant cotreatment in clinical practice. Polypharmacy with 2 antidepressants with similar mechanisms has already been discouraged by various associations, and these data pinpoint the superfluous nature of polypharmacy of 2 antidepressants, encouraging both the attempt to reduce dual prescriptions and to study the outcome in patients in whom cotreatment is discontinued versus those staying on dual treatment.


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