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Review
. 2023 Mar 6:13:20451253231154125.
doi: 10.1177/20451253231154125. eCollection 2023.

The potential of ketamine for posttraumatic stress disorder: a review of clinical evidence

Anya Ragnhildstveit  1   2   3 , Jeremy Roscoe  1   4 , Lisa C Bass  1   5 , Christopher L Averill  6   7   8   9 , Chadi G Abdallah  6   7   8   9 , Lynnette A Averill  10   8   11   9
Affiliations
Review

The potential of ketamine for posttraumatic stress disorder: a review of clinical evidence

Anya Ragnhildstveit et al. Ther Adv Psychopharmacol. .

Abstract

Posttraumatic stress disorder (PTSD) is a devastating condition, for which there are few pharmacological agents, often with a delayed onset of action and poor efficacy. Trauma-focused psychotherapies are further limited by few trained providers and low patient engagement. This frequently results in disease chronicity as well as psychiatric and medical comorbidity, with considerable negative impact on quality of life. As such, off-label interventions are commonly used for PTSD, particularly in chronic refractory cases. Ketamine, an N-methyl-D-aspartate (NDMA) receptor antagonist, has recently been indicated for major depression, exhibiting rapid and robust antidepressant effects. It also shows transdiagnostic potential for an array of psychiatric disorders. Here, we synthesize clinical evidence on ketamine in PTSD, spanning case reports, chart reviews, open-label studies, and randomized trials. Overall, there is high heterogeneity in clinical presentation and pharmacological approach, yet encouraging signals of therapeutic safety, efficacy, and durability. Avenues for future research are discussed.

Keywords: clinical evidence; esketamine; ketamine; pharmacotherapy; posttraumatic stress disorder (PTSD); rapid-acting antidepressant (RAAD); treatment.

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Conflict of interest statement

The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AR serves as the founding director of the Integrated Research Literacy Group. CGA has served as a consultant and/or on advisory boards for Aptinyx, Genentech, Janssen, Psilocybin Labs, Lundbeck, Guidepoint, and FSV7, and as editor of Chronic Stress for Sage Publications, Inc. He also filed a patent for using mTORC1 inhibitors to augment the effects of antidepressants (20 August, 2018). LAA has served as a consultant, speaker, and/or advisory board member for Guidepoint, Transcend Therapeutics, Source Research Foundation, Reason for Hope, Beond, The Cohen Foundation, Ampelis, and NPSYT, PLLC. All other authors declare no conflicts.

Figures

Figure 1.
Figure 1.
Distribution of studies investigating ketamine in posttraumatic stress disorder (PTSD) over time by publication year.
Figure 2.
Figure 2.
Number of studies investigating ketamine in posttraumatic stress disorder (PTSD) by study design and trauma type. cPTSD, civilian posttraumatic stress disorder; mPTSD, military posttraumatic stress disorder; xPTSD, mixed civilian and military posttraumatic stress disorder.
Figure 3.
Figure 3.
Percentage of studies investigating ketamine in posttraumatic stress disorder (PTSD) by study design and route of administration. IM, intramusculara; IN, intranasal; IN-IV, intranasal and intravenous; IV, intravenous; SL, sublingual. aExcluding two chart reviews with unspecified administration routes.
Figure 4.
Figure 4.
Number of patients with posttraumatic stress disorder (PTSD) treated with ketamine in retrospective versus prospective studies by dosing, using single or repeated schedules.
Figure 5.
Figure 5.
Cumulative percentage of studies investigating ketamine in posttraumatic stress disorder (PTSD) by study design and pharmacological approach, administering ketamine with or without psychotherapy.
See this image and copyright information in PMC

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