Augmenting the Treatment of PTSD with Ketamine—a Review

Or Duek, Benjamin Kelmendi, Robert H. Pietrzak & Ilan Harpaz-Rotem 

Published 10 May 2019 | DOI 10.1007/s40501-019-00172-0



Posttraumatic stress disorder (PTSD) is a debilitating psychiatric disorder with a lifetime prevalence of 6.1% in the general adult population. Clinical guidelines for the treatment of PTSD suggest the use of trauma-focused psychotherapies such as prolonged exposure (PE) and cognitive-behavioral therapy (CBT). As a second-level intervention, these guidelines suggest the use of psychotropic medications, mainly selective serotonin reuptake inhibitors (SSRIs). To date, however, studies have shown that both psychotherapeutic and psychopharmacologic treatments have limited efficacy, with remission rates around 40–70% and dropout rates of up to 50%. This paper reviews a new and emerging treatment approach of medication-augmented psychotherapy for PTSD, with an emphasis on augmenting prolonged exposure therapy (PE) with sub-anesthetic ketamine infusion. Based on animal and human research on fear extinction and memory reconsolidation, neurobiological changes that emerge following a ketamine infusion can enhance learning and thus benefit exposure-based psychotherapies for PTSD.


Medication-augmented exposure-based psychotherapies represent a promising direction for the treatment of PTSD, with some positive results in small-scale studies. More studies (phase 2 and 3) should be performed to determine if this multimodal treatment approach may help mitigate PTSD symptoms in trauma-exposed individuals who do not respond to standard monotherapeutic approaches.

Keywords: ketamine, PTSD, veterans, prolonged exposure


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