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Neuropsychiatric disorders

Placebo’s role in the rapid antidepressant effect

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Numerous randomized placebo-controlled studies over the past two decades have shown that ketamine has a rapid antidepressant action. However, its acute transient effects on cognition and perception are likely to unmask study-arm assignment. Now, the use of surgical anesthesia to conceal treatment assignment finds high rates of rapid antidepressant response among participants, regardless of whether they are randomized to ketamine or placebo.

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Correspondence to Gerard Sanacora.

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Competing interests

L.C. reports receiving grants from the National Institutes of Health; personal fees from the Veterans Health Administration, Chiesi, Averitas and Shionogi; and consulting fees from Pfizer outside of this article. G.S. reports receiving grants from Janssen, Merck, and Usona; and personal fees from Ancora, Aptinyx, Atai, Axsome Therapeutics, Biogen, Biohaven Pharmaceuticals, Boehringer Ingelheim International GmbH, Bristol Myers Squibb, Clexio, Cowen, Denovo Biopharma, ECR1, EMA Wellness, Engrail Therapeutics, Freedom Biosciences, Gilgamesh, Intra-Cellular Therapies, Janssen, KOA Health, Levo Therapeutics, Lundbeck, Merck, MiCure, Navitor Pharmaceuticals, Neurocrine Biosciences, Novartis, Noven Pharmaceuticals, Otsuka, Perception Neuroscience, Praxis Therapeutics, Relmada Therapeutics, Sage Pharmaceuticals, Seelos Pharmaceuticals, Valeant, Vistagen Therapeutics, and XW Lab outside of this article. G.S. also has a patent pending for a treatment method using a rapid-acting antidepressant and an mTOR inhibitor or immunosuppressant (held by Yale University).

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Sanacora, G., Colloca, L. Placebo’s role in the rapid antidepressant effect. Nat. Mental Health 1, 820–821 (2023). https://doi.org/10.1038/s44220-023-00141-w

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