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Neurobiological Mechanisms of Ketamine: Depression, Suicide, Trauma, and Chronic Stress Pathologies

Lynnette A. Averill, Christopher L. Averill, Chadi G. Abdallah

Psychiatric Annals February 1, 2020 DOI: 10.3928/00485713-20200109-02 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Review Peer reviewed
Topics Ketamine Depression Esketamine
Keywords Antidepressant Depression economics Nmda receptor Optimism Psychotherapist Hippocampus
Citations 6
Key findings Ketamine produces rapid-acting antidepressant and antisuicidal effects and may reverse the synaptic loss and dysconnectivity underlying chronic stress pathology.

Abstract

The serendipitous discovery of ketamine's robust antidepressant effects has served as a major catalyst to usher in new era of drug development and a paradigm shift in our understanding of the neurobiology of chronic stress pathology (CSP). This review provides a selective synthesis of (1) the historical foundations of N-methyl-D-aspartate receptor modulators and the path to discovering ketamine's use in psychiatry; (2) ketamine's clinical efficacy, specifically its rapid-acting antidepressant and rapid-acting antisuicidal effects; (3) a model of synaptic loss and dysconnectivity thought to underlie CSP; (4) clinically relevant biomarkers and mechanisms of action; and (5) how ketamine may be both an effective treatment to reverse and normalize CSP as well as a tool to further our understanding of depression, trauma, suicidality, and CSP. We conclude with a brief discussion of outstanding questions and the continued struggle between optimism and concern regarding ketamine's widespread utility as a pharmacologic agent. [ Psychiatr Ann . 2020;50(2):48–53.]

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