Prefrontal transcranial magnetic stimulation for depression in US military veterans – A naturalistic cohort study in the veterans health administration
Open accessAbstract
BACKGROUND: Repetitive transcranial magnetic stimulation (TMS) is an evidence-based treatment for pharmacoresistant major depressive disorder (MDD), however, the evidence in veterans has been mixed. To this end, VA implemented a nationwide TMS program that included evaluating clinical outcomes within a naturalistic design. TMS was hypothesized to be safe and provide clinically meaningful reductions in MDD and posttraumatic stress disorder (PTSD) symptoms. METHODS: Inclusion criteria were MDD diagnosis and standard clinical TMS eligibility. Of the 770 patients enrolled between October 2017 and March 2020, 68.4% (n = 521) met threshold-level PTSD symptom criteria. Treatments generally used standard parameters (e.g., left dorsolateral prefrontal cortex, 120% motor threshold, 10 Hz, 3000 pulses/treatment). Adequate dose was operationally defined as 30 sessions. MDD and PTSD symptoms were measured using the 9-item patient health questionnaire (PHQ-9) and PTSD checklist for DSM-5 (PCL-5), respectively. RESULTS: Of the 770 who received at least one session, TMS was associated with clinically meaningful (Cohen's d>1.0) and statistically significant (all p<.001) reductions in MDD and PTSD. Of the 340 veterans who received an adequate dose, MDD response and remission rates were 41.4% and 20%, respectively. In veterans with comorbid PTSD, 65.3% demonstrated clinically meaningful reduction and 46.1% no longer met PTSD threshold criteria after TMS. Side effects were consistent with the known safety profile of TMS. LIMITATIONS: Include those inherent to retrospective observational cohort study in Veterans. CONCLUSIONS: These multisite, large-scale data supports the effectiveness and safety of TMS for veterans with MDD and PTSD using standard clinical approaches.
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In a national US VA TMS study of 770 veterans receiving TMS, nearly half had mTBI, and TMS was demonstrated to be equally safe in veterans with and without mTBI.
“Specifically, in a national US VA TMS study of 770 veterans receiving TMS, nearly half had mTBI, and TMS was demonstrated to be equally safe in veterans with and without mTBI [64].”
From Frontal Pole Neuromodulation for Impulsivity and Suicidality in Veterans With Mild Traumatic Brain Injury and Common Co-Occurring Mental Health Conditions: Protocol for a Pilot Randomized Controlled Trial (2024) · cites this paper as [64]
The Abstract (Results) reports 770 veterans receiving at least one TMS session, and Results (Safety) reports significant adverse outcomes in fewer than 1% of patients overall. Our copy does not report that nearly half had mTBI or compare safety between veterans with and without mTBI; searches for mTBI and traumatic brain injury did not find such an analysis. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn military and veteran populations, benefit has been reported in individuals with co-occurring PTSD, depression, and mild TBI.
“in military and veteran populations, benefit has been reported in individuals with co-occurring PtsD, depression, and mild tBi”
From Feasibility, tolerability, and preliminary effectiveness of an accelerated bilateral intermittent theta-burst stimulation protocol in adults with posttraumatic stress disorder and comorbid depressive disorder following mild traumatic brain injury (2026) · cites this paper as Madore et al. 2022
The Discussion reports clinically meaningful benefit from TMS in veterans with co-occurring PTSD and depression, and the Results report improvements in both symptom domains. The paper does not report outcomes for patients who also had mild TBI, so it does not support that part of the claim (searched: TBI, traumatic brain injury, concussion). (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe present cohort required the co-occurrence of PTSD, depressive disorder, and TBI, whereas much of the published evidence derives from cohorts selected for a single psychiatric diagnosis or for military service.
“this cohort required the co-occurrence of PtsD, depressive disorder, and tBi, whereas much of the published evidence derives from cohorts selected for a single psychiatric diagnosis or for military service”
From Feasibility, tolerability, and preliminary effectiveness of an accelerated bilateral intermittent theta-burst stimulation protocol in adults with posttraumatic stress disorder and comorbid depressive disorder following mild traumatic brain injury (2026) · cites this paper as Madore et al. 2022
The Methods (Referral and Treatment Information; page unavailable) describe a cohort of VA patients recommended to have an MDD diagnosis, with PTSD permitted but not required. This supports the cited paper as an example of evidence from a military-veteran cohort that did not require all three conditions. It does not establish that *much* of the published evidence uses such cohorts; the requirement for PTSD, depression, and TBI describes the citing authors’ own cohort, not this source’s. (LLM, conf=0.82)
Experimental — accuracy not yet measuredTBI status has not been shown to eliminate symptomatic response to TMS.
“and tBi status has not been shown to eliminate symptomatic response”
From Feasibility, tolerability, and preliminary effectiveness of an accelerated bilateral intermittent theta-burst stimulation protocol in adults with posttraumatic stress disorder and comorbid depressive disorder following mild traumatic brain injury (2026) · cites this paper as Madore et al. 2022
The Results > Clinical Outcomes section reports symptomatic improvement after TMS and compares veterans with and without PTSD, not TBI. Searches for “TBI” and “traumatic brain injury” found no passage assessing whether TBI status affects response, so our copy does not establish the attributed claim. (LLM, conf=0.75)
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References 41 · Cited by 50
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- Authors
- Madore, M. R., Kozel, F. A., Williams, L. M., Green, L. C., George, M. S., Holtzheimer, P. E., Yesavage, J. A., & Philip, N. S.
- Affiliations
- VA Palo Alto Health Care System (US)
- Florida State University (US)
- Medical University of South Carolina (US)
- Dartmouth College (US)
- Brown University (US)
- Corresponding author
- Madore, Michelle R.
- Kozel, F. Andrew
- Philip, Noah S.
- ORCID
- Venue
- Journal of Affective Disorders
- Publisher
- Elsevier BV
- Published
- 2022-01
- Volume
- 297
- Pages
- 671-678
- ISSN
- 0165-0327 (ISSN-L)
- PMC
- PMC8667345
- OpenAlex
- W3210367424
- Cited by
- 50
- References
- 41
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 15 · 2023: 12 · 2022: 5
- FWCI
- 3.20
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Affective Disorders (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01 MH120126, VA I01 CX002088)
- US Department of Veterans Affairs
- Topics
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
- Keywords
- repetitive transcranial magnetic stimulation, major depressive disorder, post-traumatic stress disorder, military veterans, prefrontal cortex stimulation, treatment response and remission, TMS safety, Veterans Health Administration
- MeSH terms
- Dorsolateral Prefrontal Cortex, Depression, Depressive Disorder, Major, Major Depressive Disorder, Humans, Retrospective Studies, Stress Disorders, Post-Traumatic, Veterans, Cohort Studies, Treatment Outcome, Prefrontal Cortex, Transcranial Magnetic Stimulation, Veterans Health
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