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

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.

Rapid and sustained reduction of treatment-resistant PTSD symptoms after intravenous ketamine in a real-world, psychedelic paradigm

“…These factors-preparation, integration, and mystical-type experiences-are established correlates of therapeutic outcomes in converging psychedelic and ketamine literature (Haijen et al, 2018;Dakwar et al, 2014;Mathai et al, 2020;Rothberg et al, 2021;Marguilho et al, 2023). While the retrospective nature of this study requires cautious interpretation, the data suggest that intravenous ketamine delivered in a psychedelic paradigm, unlike typical research protocols, may produce significantly larger effects than those documented previously (Ragnhildstveit et al, 2023).…”

“…This retrospective chart review examined the largest set of real-world outcomes to date for treatment-resistant PTSD patients receiving intravenous ketamine (Ragnhildstveit et al, 2023). 117 outpatients received ketamine therapy in a highly supportive, real-world clinic environment, with the hallmarks of psychedelic therapy-including eye shades, headphones, intention setting, preparation and integration, a supportive care team, and moderately high doses.…”

The Impact of Ketamine for Treatment of Post-Traumatic Stress Disorder: A Systematic Review With Meta-Analyses

“…Ketamine is noncompetitive channel blocker of N-methyl-D-aspartate (NMDA) receptors and induces dissociative and psychotomimetic effects including alterations in visual and auditory stimuli. 5 These NMDA effects partly reverse the glutamatergic and gamma aminobutyric acid dysfunction found in patients with anxiety and depression. Ketamine is FDA-approved as an anesthetic and anesthesia induction agent but it is used off label for acute pain and treatment resistant depression.…”

Functional brain changes after alternative pharmacological interventions in posttraumatic stress disorder: A systematic review of clinical trials

“…More recently, ketamine has been proposed as a new option to treat chronic PTSD (Ragnhildstveit et al, 2023). This non-competitive antagonist of the N-methyl-D-aspartate glutamate receptor can reverse the effects of trauma and chronic stress on the amygdala, hippocampus, and prefrontal cortex (Duman et al, 2012), thus improving mood and fear learning by promoting neurogenesis, synaptogenesis, and cell proliferation (Clarke et al, 2017;Duman et al, 2012).…”

“…Low dose of delta‐9‐tetrahydrocannabinol (THC), the psychoactive constituent of cannabis, significantly reduces amygdala reactivity to social cues of threat and fear inhibition tasks (Rabinak et al., 2014 , 2020 ). More recently, ketamine has been proposed as a new option to treat chronic PTSD (Ragnhildstveit et al., 2023 ). This non‐competitive antagonist of the N ‐methyl‐ d ‐aspartate glutamate receptor can reverse the effects of trauma and chronic stress on the amygdala, hippocampus, and prefrontal cortex (Duman et al., 2012 ), thus improving mood and fear learning by promoting neurogenesis, synaptogenesis, and cell proliferation (Clarke et al., 2017 ; Duman et al., 2012 ).…”