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Review
. 2022 Jul 28:13:833259.
doi: 10.3389/fpsyt.2022.833259. eCollection 2022.

Ketamine as a prophylactic resilience-enhancing agent

Audrey G Evers  1 , James W Murrough  1   2 , Dennis S Charney  1   2   3 , Sara Costi  1   4   5
Affiliations
Review

Ketamine as a prophylactic resilience-enhancing agent

Audrey G Evers et al. Front Psychiatry. .

Abstract

Stress exposure is one of the greatest risk factors for psychiatric illnesses, including major depressive disorder (MDD) and posttraumatic stress disorder (PTSD). Enhancing stress resilience could potentially protect against the development of stress-induced psychiatric disorders, yet no resilience-enhancing pharmaceuticals have been developed to date. This review serves to consider the existing evidence for a potential pro-resilience effect of ketamine in rodents as well as the preliminary evidence of ketamine as a prophylactic treatment for postpartum depression (PPD) in humans. Several animal studies have demonstrated that ketamine administered 1 week prior to a stressor (e.g., chronic social defeat and learned helplessness) may protect against depressive-like behavior. A similar protective effect has been demonstrated against PTSD-like behavior following Contextual Fear Conditioning (CFC). Recent work has sought to explore if the administration of ketamine prevented the development of postpartum depression (PPD) in humans. Researchers administered ketamine immediately following caesarian-section and found a significantly reduced prevalence of PPD in the ketamine-treated groups compared to the control groups. Utilizing ketamine as a resilience-enhancing treatment may have unique applications, including leading to a deeper understanding of the neurobiological mechanism underlying resilience. Future trials aiming to translate and replicate these findings with humans are warranted.

Keywords: ketamine; prevention; prophylactic; resilience; stress.

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Conflict of interest statement

DC (Dean of Icahn School of Medicine at Mount Sinai) is a named co-inventor on several issued U.S. patents and several pending U.S. patent applications filed by the Icahn School of Medicine at Mount Sinai (ISMMS) related to ketamine and esketamine for treatment-resistant depression, suicidal ideation, and other disorders. ISMMS has entered into a licensing agreement with Janssen Pharmaceuticals, Inc. and it has and will receive payments from Janssen under the license agreement related to these patents. As a co-inventor, DC is entitled to a portion of the payments received by the ISMMS. Since SPRAVATO (esketamine) has received regulatory approval for treatment-resistant depression, ISMMS and DC as its employee and a co-inventor, will be entitled to additional payments, under the license agreement. SC has provided consultation services for Guidepoint and TCG Crossover. In the past 5 years, JM has provided consultation services and/or served on advisory boards for Allergan, Boehreinger Ingelheim, Clexio Biosciences, Fortress Biotech, FSV7, Global Medical Education (GME), Otsuka, and Sage Therapeutics. JM is named on a patent pending for neuropeptide Y as a treatment for mood and anxiety disorders and on a patent pending for the use of ezogabine and other KCNQ channel openers to treat depression and related conditions.

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