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 Peer reviewed DOI: 10.3928/00485713-20200109-02 via OpenAlex
Summary
Ketamine has been found to have strong antidepressant effects, leading to significant changes in drug development and our understanding of chronic stress pathology. The review discusses ketamine's rapid-acting effects on depression and suicidality, the underlying mechanisms of chronic stress, and potential biomarkers. It highlights ketamine's role in both treating chronic stress pathology and enhancing our understanding of related mental health issues, while also addressing ongoing concerns about its broad use.
Study at a glance
| Design | review |
|---|---|
| Key finding | Ketamine demonstrates rapid-acting antidepressant and antisuicidal effects, influencing both treatment approaches and our understanding of 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.]