JAMA psychiatry

Esketamine alone for adults with hard-to-treat depression: a randomized clinical trial

Updated

Abstract

In a trial with 378 participants, esketamine nasal spray showed a significant reduction in depressive symptoms compared to placebo.

  • At day 28, the 56 mg dose of esketamine resulted in a mean difference of -5.1 in depression scores compared to placebo.
  • The 84 mg dose of esketamine showed a mean difference of -6.8 in depression scores at day 28, both with P values less than .001.
  • Effect sizes for the 56 mg and 84 mg doses were observed at 0.48 and 0.63, respectively.
  • At day 2, significant differences in depression scores were noted for both doses of esketamine compared to placebo.
  • Common adverse effects of esketamine included nausea (24.8%), dissociation (24.3%), dizziness (21.7%), and headache (19.0%).

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Funding

Competing interests

Conflict of Interest Disclosures: Drs Janik, Qiu, Popova, Drevets, Canuso, and Fu and Ms Lane are employees of Johnson & Johnson, and all are stockholders of Johnson & Johnson. Drs Janik, Popova, Drevets, Canuso, and Fu report holding a patent for esketamine for treatment of depression, the rights of which were assigned to Johnson & Johnson. Dr Macaluso reported receiving grant support for research from Alto, Autobahn, Boehringer Ingelheim, Janssen, LivaNova, Merck, Neurocrine, the US National Institutes of Health (NIH)/National Institute of Mental Health (NIMH), Otsuka, the Patient-Centered Outcomes Research Institute (PCORI), and Supernus/Navitor (all clinical trial payments made to the University of Alabama at Birmingham); providing consultancy to edYOU, EmbodyXR, Intra-Cellular Therapies Inc, LivaNova, NuSachi Labs, PharmaTher, Residents Medical, Tactical Mind Solutions, and the University of Missouri; receiving personal fees from Alfa Sigma, edYOU, and LivaNova; receiving nonfinancial support from electroCore for an investigator-initiated trial; holding a patent for intravenous ketamine for amyotrophic lateral sclerosis (held under his and other faculty members’ names by University of Kansas School of Medicine); serving on Janssen’s speakers bureau for esketamine from April 2019 to June 2020; and receiving royalties from Springer Nature and the American Psychiatric Association Publishing (for textbooks published). Dr Mattingly reported receiving grant support for research from AbbVie, Acadia, Akilli, Alkermes, Alto Therapeutics, Autobahn, Avanir, Axsome, Boehringer Ingelheim, Cingulate, Click Therapeutics, Compass, Corium, Emalex, Idorsia, Intra-Cellular Therapies Inc, Johnson & Johnson Innovative Medicine, Karuna, Lumos Labs, Medgenics, Neumora, Neurocrine, NLS Pharma, Otsuka, Redax, Relmada, Roche, Sage, Sirtsei, Sumitomo, Sunovion, Supernus, Takeda, and Teva; providing consultancy to AbbVie, Acadia, Akilli, Alkermes, Angelini, Axsome, Aytu, Biogen, Boehringer Ingelheim, Cerevel, Corium, Eisai, Ironshore, Intra-Cellular Therapies Inc, Janssen, LivaNova, Lumos Labs, Lundbeck, Manus, Neurocrine, Noven, Otsuka, Redax, Relmada, Revibe, Roche, Sage, Sirona, Sky Therapeutics, Sunovion, Supernus, Takeda, Teva, and Tris Pharma; and serving on the speakers bureau for AbbVie, Alkermes, Angelini, Axsome, Corium, Intra-Cellular Therapies Inc, Ironshore, Janssen, Lundbeck, Luye, Neurocrine, Noven, Otsuka, Sunovion, Supernus, Takeda, Teva, and Tris Pharma. Dr Shelton reported receiving grant support for research from AbbVie, Alto Pharmaceuticals, Boehringer Ingelheim, Denovo Biopharma, Gate Neuroscience, INmune Bio, Intra-Cellular Therapies Inc, Johnson & Johnson Innovative Medicine, LivaNova PLC, NIMH, Navitor Pharmaceuticals, Neumora, Neurocrine Biosciences, NeuroRx, the NIH, Novartis AG, NRx Pharmaceuticals, Otsuka Pharmaceuticals, PCORI, Sumitomo Pharma America, and Supernus Pharmaceuticals; providing consultancy to Boehringer Ingelheim, Denovo Biopharma, EQUULUS Therapeutics, Evecxia Therapeutics, Johnson & Johnson Innovative Medicine, NeuroRx, Novartis AG, Otsuka Pharmaceuticals, Seelos Therapeutics, Sumitomo Pharma America, and Supernus Pharmaceuticals; and receiving royalties from Springer Nature Group and Wolters-Kluwer NV. Dr Zajecka reported receiving grant support for research from Abbott, Axsome, Boehringer Ingelheim, the Cheryl T. Herman Foundation, COMPASS Pathfinder Limited, Cybin IRL Limited, ElMindA, Hoffman-LaRoche, Johnson & Johnson/Janssen, LivaNova, Neurocrine, Novartis, Otsuka, Praxis, SAGE Therapeutics, and Takeda and providing consultancy to/advisory board participation for Alpha Sigma, ElMindA, Johnson & Johnson/Janssen, and Paragon. No other disclosures were reported.
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