What’s New in Treating Depression? Another Argument for Keeping Things Simple

I just read the story in the July 1 issue of Psychiatric News that antidepressant combinations are less well tolerated and no more effective than monotherapy [1]. The information is from a study published in the American Journal of Psychiatry [2]. It was a single blind study with 650 outpatients and a selective serotonin reuptake inhibitor (SSRI) as monotherapy was compared with two antidepressant combinations. The combination of Venlafaxine-plus-Mirtazapine was poorly tolerated. This same group of researchers also found in a secondary analysis that combination of antidepressants didn’t work any better for treatment of depression with melancholic features [3].

This makes an argument for trying to keep things simple in treating recurrent major depressive disorder at the outset by thinking twice before beginning pharmacotherapy with combinations of antidepressants. This is a far cry from Stahl’s paper which argued only a few years ago to try combinations initially [4]. In fact, one of the take home points of that short article was that “Evidence is accumulating now that patients starting combination therapy from the very initiation of treatment for major depression may experience enhanced outcomes, attaining higher remission rates and lower relapse rates than with single antidepressants”.

The lesson here is that new research is constantly making and breaking paradigms and that the early adopters of new strategies are not always in the best position to lead the rank and file.

1. Sinclair, L., Antidepressant Combinations Offer No Advantage Over Monotherapy, in Psychiatric News 2011, American Psychiatric Association: Arlington, Va.

2. Rush, A.J., 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(7): p. 689-701.

3. Bobo, W.V., et al., Randomized comparison of selective serotonin reuptake inhibitor (escitalopram) monotherapy and antidepressant combination pharmacotherapy for major depressive disorder with melancholic features: A CO-MED report. Journal of Affective Disorders. In Press, Corrected Proof.

4. Stahl, S.M., Combining antidepressant therapies from the initiation of treatment: a paradigm shift for major depression. J Clin Psychiatry, 2009. 70(11): p. 1493-4.