Psychiatry and Clinical Psychopharmacology
Systematic Review

Interventional Psychiatry and Emerging Treatments for Posttraumatic Stress Disorder (PTSD): A Systematic Review

1.

Interventional Psychiatry Program, St. Michael’s Hospital, Toronto, Canada

2.

Mental Health and Addictions Services, St. Michael’s Hospital, Toronto, Canada

3.

University of Alberta, Department of Psychiatry, Edmonton, Alberta, Canada

4.

Neuroscience and Mental Health Institute (NMHI), University of Alberta, Edmonton, Canada

5.

University of Alberta, Department of Psychiatry, Edmonton, Alberta-Canada

6.

University of Ottawa Institute of Mental Health Research at the Royal, Ottawa, Canada

7.

Department of Psychiatry, University of Manitoba, Winnipeg, Canada

8.

Atlas Institute for Veterans and Families, Ottawa, Canada

9.

Department of Psychiatry, Leiden University Medical Center (LUMC), Leiden, the Netherlands

10.

Department of Psychiatry, Western University, London, Canada

11.

Department of Neuroscience, University of Western Ontario, London, Canada

12.

Homewood Health Research Institute, Ontario, Canada

13.

Department of Psychiatry, University of Toronto, Toronto, Canada

Psychiatry and Clinical Psychopharmacology 2025; 35: Supplement S57-S89
DOI: 10.5152/pcp.2025.241027
Read: 16 Downloads: 6 Published: 11 August 2025

Background: Posttraumatic stress disorder (PTSD) is a severe, often difficult-to-treat condition, highlighting the need for innovative therapies. Interventional treatments, including neuromodulation, rapid-acting pharmacotherapies such as intravenous ketamine (IV-KET) and esketamine (ESK), and emerging psychedelic-assisted psychotherapies, offer promising solutions. This systematic review evaluates the efficacy, safety, and future research priorities of these treatments for PTSD.

Methods: A search strategy was implemented across 3 electronic databases. Peer-reviewed articles written in English that focused on interventional psychiatry treatments for adult patients with PTSD were included.

Results: The systematic review encompassed 94 studies, including 39 on transcranial magnetic stimulation (TMS), 8 on IV-KET, 3 on intranasal esketamine (IN-ESK), 4 on intravenous ketamine (IV-KET) assisted therapy (KET-AT), 1 on esketamine (ESK) assisted therapy (ESK-AT), and 14 on 3,4-methylenedioxymethamphetamine assisted therapy (MDMA-AT). Randomized controlled trials demonstrated response rates of 12.5%-80% for TMS, 17%-67% for IV-KET, and 50%-87% for MDMA. Additional treatments reviewed included Electroconvulsive Therapy, transcranial direct current stimulation, and other pharmacological and neurostimulation treatments. Most treatments were well tolerated, with only mild, transient adverse effects.

Conclusions: This review highlights the heterogeneity in efficacy, safety, and tolerability across neuromodulation and pharmacologic treatments for PTSD. Variability in response rates reflects differences in patient populations, protocols, and comorbidities. While repetitive TMS, IV-KET, ESK, KET-AT, and MDMA-AT show symptom improvement, sustained efficacy varies, underscoring the need for maintenance strategies. Although direct evidence on stage-specific approaches is limited, these methods, guided by neuroscience-based nomenclature, may improve therapeutic precision, especially in complex cases.

Cite this article as: Janssen-Aguilar R, Meshkat S, Al-Shamali HF, et al. Interventional psychiatry and emerging treatments for post-traumatic stress disorder (PTSD): A systematic review. Psychiatry Clin Psychopharmacol. 2025;35(Suppl. 1):S57-S89.

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