Current Treatment Options in Psychiatry

, Volume 6, Issue 2, pp 143–153 | Cite as

Augmenting the Treatment of PTSD with Ketamine—a Review

  • Or Duek
  • Benjamin Kelmendi
  • Robert H. Pietrzak
  • Ilan Harpaz-RotemEmail author
PTSD (S Creech and L Sippel, Section Editors)
Part of the following topical collections:
  1. Topical Collection on PTSD



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.


PTSD Ketamine Prolonged exposure Augmenting psychotherapy MDMA DCS 


Compliance with Ethical Standards

Conflict of Interest

Or Duek declares that he has no conflict of interest. Benjamin Kelmendi declares that he has no conflict of interest. Ilan Harpaz-Rotem declares that he has no conflict of interest. Robert H. Pietrzak is a scientific consultant with Cogstate and received payment from them.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


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Authors and Affiliations

  • Or Duek
    • 1
  • Benjamin Kelmendi
    • 1
  • Robert H. Pietrzak
    • 1
    • 2
  • Ilan Harpaz-Rotem
    • 1
    • 2
    Email author
  1. 1.Department of PsychiatryYale University School of MedicineNew HavenUSA
  2. 2.US Department of Veterans Affairs National Center for PTSDVA Connecticut Healthcare SystemWest HavenUSA

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