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Ketamine’s Mechanism of Rapid Antidepressant Activity: Evidence Gleaned from Clinical Studies

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Ketamine for Treatment-Resistant Depression

Abstract

The discovery of antidepressant medications more than 50 years ago was one of the major breakthroughs in medical science. Today, the field of antidepressant drug development is experiencing a paradigm shift. Changing perceptions regarding the neurobiology of depression and the serendipitous discovery of ketamine’s rapid antidepressant effects have ushered in a new era of innovative research and novel drug development. This chapter provides a selective review of the suspected mechanisms of ketamine’s rapid antidepressant action in human subjects gleaned from multiple controlled and open-label trials. We also briefly review the underlying neurobiology of depression, potential biomarkers of ketamine response, the efficacy and safety profile of ketamine, current limitations to its widespread use, and considerations for novel drug development that hold promise for improved psychotherapeutic treatments for depressive and trauma-related disorders.

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Authors and Affiliations

  1. Clinical Neurosciences Division, VA National Center for PTSD, West Haven, CT, USA

    Lynnette A. Averill & Chadi G. Abdallah MD

  2. Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA

    Lynnette A. Averill & Chadi G. Abdallah MD

  3. Mood and Anxiety Disorders Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    James W. Murrough

  4. Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    James W. Murrough

  5. Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    James W. Murrough

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  1. Lynnette A. Averill
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  3. Chadi G. Abdallah MD
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Correspondence to Chadi G. Abdallah MD .

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  1. Baylor College of Medicine and Michael E. Debakey VA Medical Center, Houston, Texas, USA

    Sanjay J. Mathew

  2. National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA

    Carlos A. Zarate, Jr.

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Averill, L.A., Murrough, J.W., Abdallah, C.G. (2016). Ketamine’s Mechanism of Rapid Antidepressant Activity: Evidence Gleaned from Clinical Studies. In: Mathew, S., Zarate, Jr., C. (eds) Ketamine for Treatment-Resistant Depression. Adis, Cham. https://doi.org/10.1007/978-3-319-42925-0_7

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