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Comment & Response
June 8, 2022

Combination Antidepressant Therapy vs Monotherapy—Further Considerations—Reply

Author Affiliations
  • 1Department of Psychiatry and Psychotherapy, University of Cologne Medical School, Cologne, Germany
  • 2Charité University Medicine, St Hedwig-Krankenhaus, Clinic for Psychiatry and Psychotherapy, Berlin, Germany
  • 3Department of Psychiatry and Psychotherapy, University Hospital of Dresden, Dresden, Germany
JAMA Psychiatry. 2022;79(8):832-833. doi:10.1001/jamapsychiatry.2022.1385

In Reply We appreciate the pharmacological and design-related input voiced in the 3 letters. It is an opportunity to clarify and emphasize key aspects of our systematic review and meta-analysis.1

As Cowen suggested, we calculated the meta-analysis without the 2 trazodone randomized clinical trials (RCTs) and arrived at practically the same summary estimate for presynaptic α2-autoreceptors (RI+α2) combinations vs monotherapy: a standardized mean difference (SMD) of 0.36 (95% CI, 0.18-0.55) in 16 studies compared with an SMD of 0.37 (95% CI, 0.19-0.55) in 18. We agree that additional 5-HT2A receptor blockade as a mechanism in antidepressant combination therapy with mirtazapine, mianserin, or trazodone may be a promising subject for further research.

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