Effects of Intravenous Ketamine on Posttraumatic Stress Disorder (PTSD): A Systematic Review

Liyang Yin¹, Andy Lu^{1

2}, Gia Han Le^{1

3

4}, Christine E Dri¹, Sabrina Wong^{1

4

5}, Kayla M Teopiz^{1

3}, Heidi Xu^{1

5}, Roger Ho^{6

7

8}, Taeho Greg Rhee^{9

10}, Heidi Ka Ying Lo¹¹, Maria-Christina Sioufi^{1

12}, Yang Jing Zheng^{1

3}, Hezekiah C T Au^{1

3

13

14}, Hernan F Guillen-Burgos^{15

16

17}, Bing Cao¹⁸, Roger S McIntyre^{5

19}

Affiliations

¹ Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada.
² Department of Psychology, University of Western Ontario, London, Ontario, Canada.
³ Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
⁴ Poul Hansen Family Centre for Depression, University Health Network, Toronto, Ontario, Canada.
⁵ Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
⁶ Department of Psychological Medicine, National University of Singapore, Singapore, Singapore.
⁷ Institute for Health Innovation and Technology (iHealthtech), National University of Singapore, Singapore, Singapore.
⁸ Division of Life Science (LIFS), Faculty of Science, Hong Kong University of Science and Technology, Hong Kong, China.
⁹ Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut, USA.
¹⁰ Department of Public Health Sciences, University of Connecticut School of Medicine, Farmington, Connecticut, USA.
¹¹ Department of Psychiatry, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
¹² Department of Human Biology and Physiology, University of Toronto, Toronto, Ontario, Canada.
¹³ Joint Department of Medical Imaging, University of Toronto, Toronto, Canada.
¹⁴ Division of Neurosurgery, Department of Surgery, University Health Network and University of Toronto, Toronto, Ontario, Canada.
¹⁵ Department of Psychiatry and Mental Health, Pontificia Universidad Javeriana, Bogota, Colombia.
¹⁶ Center for Clinical and Translational Research, Universidad Simon Bolivar, Barranquilla, Colombia.
¹⁷ Center for Clinical and Translational Research, Bogota, Colombia.
¹⁸ School of Psychology and Key Laboratory of Cognition and Personality (Ministry of Education), Southwest University, Chongqing, P. R. China.
¹⁹ Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.

PMID: 41326978
DOI: 10.1111/acps.70053

Review

Effects of Intravenous Ketamine on Posttraumatic Stress Disorder (PTSD): A Systematic Review

Liyang Yin et al. Acta Psychiatr Scand. 2025.

. 2025 Dec 1.

doi: 10.1111/acps.70053. Online ahead of print.

Authors

Affiliations

¹ Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada.
² Department of Psychology, University of Western Ontario, London, Ontario, Canada.
³ Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
⁴ Poul Hansen Family Centre for Depression, University Health Network, Toronto, Ontario, Canada.
⁵ Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
⁶ Department of Psychological Medicine, National University of Singapore, Singapore, Singapore.
⁷ Institute for Health Innovation and Technology (iHealthtech), National University of Singapore, Singapore, Singapore.
⁸ Division of Life Science (LIFS), Faculty of Science, Hong Kong University of Science and Technology, Hong Kong, China.
⁹ Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut, USA.
¹⁰ Department of Public Health Sciences, University of Connecticut School of Medicine, Farmington, Connecticut, USA.
¹¹ Department of Psychiatry, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
¹² Department of Human Biology and Physiology, University of Toronto, Toronto, Ontario, Canada.
¹³ Joint Department of Medical Imaging, University of Toronto, Toronto, Canada.
¹⁴ Division of Neurosurgery, Department of Surgery, University Health Network and University of Toronto, Toronto, Ontario, Canada.
¹⁵ Department of Psychiatry and Mental Health, Pontificia Universidad Javeriana, Bogota, Colombia.
¹⁶ Center for Clinical and Translational Research, Universidad Simon Bolivar, Barranquilla, Colombia.
¹⁷ Center for Clinical and Translational Research, Bogota, Colombia.
¹⁸ School of Psychology and Key Laboratory of Cognition and Personality (Ministry of Education), Southwest University, Chongqing, P. R. China.
¹⁹ Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.

PMID: 41326978
DOI: 10.1111/acps.70053

Abstract

Introduction: Posttraumatic stress disorder (PTSD) is a mental disorder resulting from exposure to traumatic events. Evidence suggests that ketamine may be efficacious in treating PTSD, however, ketamine's mechanisms in treating PTSD remain unclear. Herein, this review aims to evaluate the clinical outcomes of ketamine treatment in persons with PTSD and investigate the possible neurobiological mechanisms underlying ketamine's therapeutic effect in PTSD.

Methods: A systematic search was conducted on PubMed and OVID (MEDLINE, Embase, PsychINFO) from inception until September 2025. Randomized controlled trials reporting on the effects of intravenous ketamine to treat PTSD were included.

Results: Seven studies with a total of 323 participants were included in this review. Ketamine administration meaningfully improved PTSD symptoms in two trials as evidenced by significant improvement on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and the Impact of Event Scale-Revised (IES-R) compared to control/placebo. Multi-infusion administration schedules achieved greater clinical outcomes when compared to single-dose administration schedules. Preliminary evidence suggests that repeated lower doses (0.2mg/kg) of ketamine were more efficacious in sustaining treatment effects than standard doses (0.5mg/kg). For persons receiving ketamine, an association was observed between top-down inhibition of the amygdala originating in the ventromedial prefrontal cortex (vmPFC) and symptom improvement.

Conclusion: Our results suggest that intravenous ketamine may be efficacious in the treatment of PTSD. Subsequent studies should attempt to evaluate the additive effect of combining ketamine with psychotherapeutic interventions as well as determining mechanistic pathways mediating symptom relief in persons with PTSD.

Keywords: Ketalar; N‐methyl‐D‐aspartate (NMDA) receptor; ketamine; posttraumatic stress symptoms; post‐traumatic stress disorder; trauma‐related stress.

PubMed Disclaimer

References

1. E. Compean and M. Hamner, “Posttraumatic Stress Disorder With Secondary Psychotic Features (PTSD‐SP): Diagnostic and Treatment Challenges,” Progress in Neuro‐Psychopharmacology and Biological Psychiatry 88 (2019): 265–275.
1. C. Schrader and A. Ross, “A Review of PTSD and Current Treatment Strategies,” Missouri Medicine 118, no. 6 (2021): 546–551.
1. R. H. Pietrzak, R. B. Goldstein, S. M. Southwick, and B. F. Grant, “Prevalence and Axis I Comorbidity of Full and Partial Posttraumatic Stress Disorder in the United States: Results From Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions,” Journal of Anxiety Disorders 25, no. 3 (2011): 456–465.
1. H. F. Guillén‐Burgos and K. Gutiérrez‐Ruiz, “Avances Genéticos en el Trastorno Por Estrés Postraumático,” Revista Colombiana de Psiquiatría 47, no. 2 (2018): 108–118.
1. J. Schein, C. Houle, A. Urganus, et al., “Prevalence of Post‐Traumatic Stress Disorder in the United States: A Systematic Literature Review,” Current Medical Research and Opinion 37, no. 12 (2021): 2151–2161.

Publication types

Actions

LinkOut - more resources

Full Text Sources
- Wiley
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Effects of Intravenous Ketamine on Posttraumatic Stress Disorder (PTSD): A Systematic Review

Affiliations

Effects of Intravenous Ketamine on Posttraumatic Stress Disorder (PTSD): A Systematic Review

Authors

Affiliations

Abstract

References

Publication types

LinkOut - more resources

Full Text Sources

Miscellaneous