Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Aug 11;35(Suppl 1):S57-S89.
doi: 10.5152/pcp.2025.241027.

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

Reinhard Janssen-Aguilar  1   2 , Shakila Meshkat  1   2 , Huda F Al-Shamali  1   2 , Argyrios Perivolaris  1   2 , Jennifer Swainson  3   4 , Yanbo Zhang  3   4 , Andrew Greenshaw  3   4 , Lisa Burback  3   4 , Olga Winkler  3   4 , Jennifer L Phillips  5 , Murray W Enns  6 , Jitender Sareen  6 , Andrew Nicholson  5   7 , Eric Vermetten  8 , Rakesh Jetly  5 , Ruth Lanius  9   10   11 , Venkat Bhat  1   2   12
Affiliations

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

Reinhard Janssen-Aguilar et al. Psychiatry Clin Psychopharmacol. .

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

Declaration of Interests: Eric Vermetten and Andrew Greenshaw are Associate Editors at Psychiatry and Clinical Psychopharmacology, however, their involvement in the peer-review process was solely as authors. Reinhard Janssen, Shakila Meshkat, Huda F. Al-Shamali, Argyrios Perivolaris, Yanbo Zhang, Andrew Greenshaw, Lisa Burback, Jitendar Sareen, Olga Winkler, Ruth Lanius, Jennifer Phillips, Eric Veremetten, Andrew Nicholson and Murray W. Enns have no disclosures. Jennifer Swainson has received honoraria for speaking or advisory roles from Abbvie, Bausch Health, Biron, Eisai, Idorsia, Janssen, Lundbeck, Novo Nordisk, and Otsuka. Rakesh Jetly is the CMO of Mydecine Innovation Group. Venkat Bhat is supported by an Academic Scholar Award from the University of Toronto Department of Psychiatry and has received research funding from the Canadian Institutes of Health Research, Brain & Behavior Foundation, Ontario Ministry of Health Innovation Funds, Royal College of Physicians and Surgeons of Canada, Department of National Defence (Government of Canada), New Frontiers in Research Fund, Associated Medical Services Inc. Healthcare, American Foundation for Suicide Prevention, Roche Canada, Novartis, and Eisai.

Figures

Figure 1.
Figure 1.
Circuits, brain structures, and symptoms involved in PTSD. Abbreviations: ACC, anterior cingulate cortex; BLA, basolateral amygdala; CNA, central nucleus of the amygdala; DFM networks, default mode networks; HPA, hypothalamic-pituitary-adrenal axis; PFC, prefrontal cortex; PTSD, posttraumatic stress disorder. Adapted from Shalev A, Cho D, Marmar CR. Neurobiology and treatment of posttraumatic stress disorder. Am J Psychiatry. 2024;181(8):705-719. doi:10.1176/appi.ajp.20240536.
Figure 2.
Figure 2.
Prisma flow diagram.
Figure 3.
Figure 3.
General sample characteristics. A: Years of publication of the included studies. B: Countries of publication of the included studies. C: Instruments used to measure PTSD. D: Interventions included in the study. Results in each panel are presented as frequency values. Abbreviations: BPRS, Brief Psychiatric Rating Scale; CAPS, Clinician-Administered PTSD Scale; CGI, clinical global impressions; DTS, Davidson Trauma Scale; ECT, electroconvulsive therapy; IES, Impact of Event Scale; ITQ, International Trauma Questionnaire; KET, ketamine; LDS, Life Distress Scale; MDMA, 3,4-methylenedioxymethamphetamine; MPPSD, Mississippi PTSD Scale; PCL, PTSD checklist; PDS, Posttraumatic Diagnostic Scale; PSS, PTSD Symptom Scale; PTGI, posttraumatic growth inventory; TABS, Trauma Appraisal and Beliefs Scale; tDCS, Transcranial Direct Current stimulation; TMS, transcranial magnetic stimulation.
Figure 4.
Figure 4.
Countries and trial status presented by most frequent intervention. Panel A) Countries. Panel B) Trial status. Results in each panel are presented as frequency values. Abbreviations: ECT, electroconvulsive therapy; IV KET, intravenous ketamine; MDMA, 3,4-methylenedioxymethamphetamine; RGCT, registered clinical trial; tDCS, transcranial direct current stimulation; TMS, transcranial magnetic stimulation.
Figure 5.
Figure 5.
Response rates reported in TMS, IV KET, and MDMA randomized controlled trials that included response rate data. Abbreviations: BE, brief exposure; BL, bilateral; DTMS, deep transcranial magnetic stimulation; HF-TMS (RU), high-frequency repetitive transcranial magnetic stimulation (right unilateral); IV KET, intravenous ketamine; LF-TMS (RU), low-frequency repetitive transcranial magnetic stimulation (right unilateral); MDMA, 3,4-methylenedioxymethamphetamine; MDZ, midazolam; mg/kg, milligrams per kilogram; TE: therapy; TMS, transcranial magnetic stimulation.
See this image and copyright information in PMC

References

    1. Bryant RA. . Post-traumatic stress disorder: a state-of-the-art review of evidence and challenges. World Psychiatry. 2019;18(3):259 269. (doi: 10.1002/wps.20656) - DOI - PMC - PubMed
    1. Wen Zeng Y Chiu SH Yeh CB. . Childhood maltreatment associated with anxiety and depression and complex PTSD symptoms Psychiatry Clin Psychopharmacol. 2024;34(3):201 209. (doi: 10.1007/s40596-014-0050-x) - DOI - PMC - PubMed
    1. Çelik YS, Efe A, Aydos BS, Akbas Aliyev ES, Cura M, Harputlu Yamak Y, Demirkol Tunca R, Kaşak M, Öztürk Y. Psychiatric manifestations following the 2023 kahramanmaraş earthquakes: a focus on children and adolescents. Psychiatry Clin Psychopharmacol. 2024;34(4):302 310. (doi: 10.1007/s40596-014-0050-x) - DOI - PMC - PubMed
    1. Shalev A Cho D Marmar CR. . Neurobiology and treatment of posttraumatic stress disorder. Am J Psychiatry. 2024;181(8):705 719. (doi: 10.1176/appi.ajp.20240536) - DOI - PubMed
    1. Terhakopian A Sinaii N Engel CC Schnurr PP Hoge CW. . Estimating population prevalence of posttraumatic stress disorder: an example using the PTSD checklist. J Trauma Stress. 2008;21(3):290 300. (doi: 10.1002/jts.20341) - DOI - PubMed

LinkOut - more resources