The emergence of ketamine as a novel treatment for posttraumatic stress disorder.

A serious lack of effective pharmacotherapeutic interventions for posttraumatic stress disorder (PTSD) raises the urgent need for the development of novel treatments. Ketamine-a noncompetitive glutamate N-methyl-d-aspartate (NMDA) receptor antagonist in use for decades as an anesthetic and analgesic agent-has more recently been demonstrated to have rapid-onset antidepressant effects in patients with treatment-resistant depression (TRD). In the present review of ketamine as an emerging novel pharmacotherapeutic intervention for chronic PTSD, we discuss findings from the first proof-of-concept, randomized clinical trial (RCT) of single-dose intravenous ketamine in patients with chronic PTSD, as well as open-label studies and current practice. We introduce ongoing RCTs investigating the efficacy of repeated ketamine infusions in rapidly reducing symptoms and maintaining improvement in samples of individuals with PTSD stemming from civilian and military traumas. Additionally, we discuss mixed findings from published reports on ketamine administration in the acute aftermath of trauma. Studies in animal models of chronic stress have investigated molecular mechanisms underlying ketamine's effects, generating a shift in the conceptualization of PTSD as a disorder of impaired neural connectivity. We review animal studies examining the potential of ketamine to modify the expression of fear by altering memory reconsolidation or enhancing fear extinction, as well as others investigating ketamine administration prophylactically prior to stress exposure. We introduce the need for additional study in humans to evaluate whether ketamine might enhance the efficacy of psychotherapeutic interventions in individuals with chronic PTSD, harnessing a window of ketamine-induced neuroplasticity. While research on ketamine for PTSD is still in its early stages, it brings about the promise of novel and more effective treatments for this disabling condition.

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Déclaration de conflit d'intérêts

Conflict of interest Drs. Charney and Feder are named co-inventors on an issued patent in the United States, and several issued patents outside the United States, filed by the Icahn School of Medicine at Mount Sinai (ISMMS) for the use of ketamine as a therapy for PTSD. This intellectual property has not been licensed. In addition, Dr. Charney is named co-inventor on several issued US patents, and several pending US patent applications, filed by ISMMS for the use of ketamine as a therapy for TRD and suicidal ideation. 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, Dr. Charney is entitled to a portion of the payments received by the ISMMS. Since SPRAVATO (esketamine) has received regulatory approval for TRD, ISMMS and Dr. Charney as its employee and a co-inventor, will be entitled to additional payments, under the license agreement. Dr. Charney is named co-inventor on a patent application filed by the ISMMS for the use of intranasally administered neuropeptide Y for the treatment of mood and anxiety disorders. This intellectual property has not been licensed. Dr. Charney is a named co-inventor on several patents filed by ISMMS for a cognitive training intervention to treat depression and related psychiatric disorders. ISMMS has entered into a licensing agreement with Click Therapeutics, Inc., and has and will receive payments related to the use of this cognitive training intervention for the treatment of psychiatric disorders. In accordance with the ISMMS Faculty Handbook, Dr. Charney has received a portion of these payments and is entitled to a portion of any additional payments that the medical school might receive from this license with Click Therapeutics. Ms. Rutter and Dr. Schiller have no conflicts of interest to declare.