CoChat
Sign Up
Cited by 21Transcranial Magnetic Stimulation StudiesTraumatic Brain Injury ResearchElectroconvulsive Therapy Studies

Repetitive Transcranial Magnetic Stimulation for Depression and Posttraumatic Stress Disorder in Veterans With Mild Traumatic Brain Injury

Open access
Philip, Noah S., Ramanathan, Dhakshin, Gamboa, Bruno, Brennan, McKenna C., Kozel, Frank Andrew, Lazzeroni, Laura, Madore, Michelle R.·2023·Neuromodulation: Technology at the Neural Interface
DOI 10.1016/j.neurom.2022.11.015PMC PMC10765323
Open this paper in CoChat — free accountOpen PDF

Abstract

OBJECTIVES: Mild traumatic brain injury (mTBI) is a signature injury of military conflicts and is prevalent in veterans with major depressive disorder (MDD) and posttraumatic stress disorder (PTSD). Although therapeutic transcranial magnetic stimulation (TMS) can reduce symptoms of depression and PTSD, whether traumatic brain injury (TBI) affects TMS responsiveness is not yet known. We hypothesized mTBI would be associated with higher pretreatment symptom burden and poorer TMS response. MATERIALS AND METHODS: We investigated a registry of veterans (N = 770) who received TMS for depression across the US Veterans Affairs system. Of these, 665 (86.4%) had data on TBI and lifetime number of head injuries while 658 had complete data related to depression outcomes. Depression symptoms were assessed using the nine-item Patient Health Questionnaire and PTSD symptoms using the PTSD Checklist for DSM-5. Linear mixed effects models and t-tests evaluated whether head injuries predicted symptom severity before treatment, and how TBI status affected clinical TMS outcomes. RESULTS: Of the 658 veterans included, 337 (50.7%) reported previous mTBI, with a mean of three head injuries (range 1-20). TBI status did not predict depressive symptom severity or TMS-associated changes in depression (all p's > 0.1). TBI status was associated with a modest attenuation of TMS-associated improvement in PTSD (in patients with PTSD Checklist for DSM-5 scores > 33). There was no correlation between the number of head injuries and TMS response (p > 0.1). CONCLUSIONS: Contrary to our hypothesis, presence of mTBI did not meaningfully change TMS outcomes. Veterans with mTBI had greater PTSD symptoms, yet neither TBI status nor cumulative head injuries reduced TMS effectiveness. Limitations include those inherent to retrospective registry studies and self-reporting. Although these findings are contrary to our hypotheses, they support the safety and effectiveness of TMS for MDD and PTSD in patients who have comorbid mTBI.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.neurom.2022.11.015

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 40 · Cited by 21

Research works printed but not linked: 35

  1. [1]Hyder AA, Wunderlich CA, Puvanachandra P, Gururaj G, Kobusingye OC. The impact of traumatic brain injuries: A global perspective. NeuroRehabilitation. 2007; 22(5): 341– 353. doi: 10.3233/nre-2007-22502 18162698 · DOI · Paper page
  2. [2]Dewan MC, Rattani A, Gupta S, Baticulon RE, Hung Y, Punchak M, Estimating the global incidence of traumatic brain injury. J Neurosurg. 2019; 130(4): 1080– 1097. doi: 10.3171/2017.10.jns17352 29701556 · DOI
  3. [3]Voss JD, Connolly J, Schwab KA, Scher AI. Update on the epidemiology of concussion/mild traumatic brain injury. Curr Pain and Headache Rep. 2015; 19(7): 32. doi: 10.1007/s11916-015-0506-z 26049775 · DOI
  4. [4]Laker SR. Epidemiology of concussion and mild traumatic brain injury. PM&R. 2011; 3(10 Suppl 2): S354– S358. doi: 10.1016/j.pmrj.2011.07.017 22035677 · DOI
  5. [5]Costello K, Greenwald BD. Update on domestic violence and traumatic brain injury: A narrative review. Brain Sciences. 2022; 12(1): 122. doi: 10.3390/brainsci12010122 35053865 PMC8773525 · DOI
  6. [6]Cancelliere C, Coronado VG, Taylor CA, Xu L. Epidemiology of isolated versus nonisolated mild traumatic brain injury treated in emergency departments in the United States, 2006–2012: Sociodemographic characteristics. Journal of Head Trauma Rehabilitation. 2017; 32(4): E37– E46. doi: 10.1097/htr.0000000000000260 28489698 PMC5554936 · DOI
  7. [7]Hoge CW, McGurk D, Thomas JL, Cox AL, Engel CC, Castro CA. Mild traumatic brain injury in U.S. Soldiers returning from Iraq. N Engl J Med. 2008; 358(5): 453– 463. doi: 10.1056/NEJMoa072972 18234750 · DOI · Paper page
  8. [9]Stein MB, Jain S, Giacino JT, Levin H, Sureyya D, Nelson LD, Risk of posttraumatic stress disorder and major depression in civilian patients after mild traumatic brain injury: A TRACK-TBI study. JAMA Psychiatry. 2019; 76(3): 249– 258. doi: 10.1001/jamapsychiatry.2018.4288 30698636 PMC6439818 · DOI · Paper page
  9. [10]Friedrich MJ. Depression Is the leading cause of disability around the world. JAMA. 2017; 317(15): 1517. doi: 10.1001/jama.2017.3826 28418490 · DOI · Paper page
  10. [11]Nichter B, Norman S, Haller M, Pietrzak RH. Physical health burden of PTSD, depression, and their comorbidity in the U.S. veteran population: Morbidity, functioning, and disability. J Psychosom Res. 2019; 124:109744. doi: 10.1016/j.jpsychores.2019.109744 31443821 · DOI
  11. [12]Goldberg J, Magruder KM, Forsberg CW, Kazis LE, Ustun TB, Friedman MJ, The association of PTSD with physical and mental health functioning and disability (VA Cooperative Study #569: the course and consequences of posttraumatic stress disorder in Vietnam-era veteran twins). Qual Life Res. 2014; 23(5): 1579– 1591. doi: 10.1007/s11136-013-0585-4 24318083 PMC5873962 · DOI
  12. [13]George MS, Lisanby SH, Avery D, McDonald WM, Durkalski V, Pavlicova M, Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: A sham-controlled randomized trial. Arch Gen Psychiatry. 2010; 67(5): 507– 516. doi: 10.1001/archgenpsychiatry.2010.46 20439832 · DOI · Paper page
  13. [14]O’Reardon JP, Solvason HB, Janicak PG, Sampson S, Isenberg KE, Nahas Z, Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: A multisite randomized controlled trial. Biol Psychiatry. 2007; 62(11): 1208– 1216. doi: 10.1016/j.biopsych.2007.01.018 17573044 · DOI · Paper page
  14. [15]Cosmo C, Zandvakili A, Petrosino NJ, Berlow YA, Philip NS. Repetitive transcranial magnetic stimulation for treatment-resistant depression: Recent critical advances in patient care. Curr Treat Options Psychiatry. 2021; 8(2): 47– 63. doi: 10.1007/s40501-021-00238-y 33723500 PMC7946620 · DOI
  15. [16]Madore MR, Kozel FA, Williams LM, Green LC, George MS, Holtzheimer PE, Prefrontal transcranial magnetic stimulation for depression in US military veterans - A naturalistic cohort study in the veterans health administration. J Affect Disord. 2022; 297: 671– 678. doi: 10.1016/j.jad.2021.10.025 34687780 PMC8667345 · DOI · Paper page
  16. [18]Petrosino NJ, Cosmo C, Berlow YA, Zandvakili A, van ‘t Wout-Frank M, Philip NS. Transcranial magnetic stimulation for post-traumatic stress disorder. Ther Adv Psychopharmacol. 2021; 11:20451253211049921. doi: 10.1177/20451253211049921 PMC8558793 34733479 · DOI
  17. [19]Leung A, Metzger-Smith V, He Y, Cordero J, Ehlert B, Song D, Left dorsolateral prefrontal cortex rTMS in alleviating mTBI related headaches and depressive symptoms. Neuromodulation. 2018; 21(4): 390– 401. doi: 10.1111/ner.12615 28557049 · DOI
  18. [20]Fitzgerald PB, Hoy KE, Maller JJ, Herring S, Segrave R, McQueen S, Transcranial magnetic stimulation for depression after a traumatic brain injury: A case study. J ECT. 2011; 27(1): 38– 40. doi: 10.1097/YCT.0b013e3181eb30c6 20938348 · DOI
  19. [21]Siddiqi SH, Trapp NT, Hacker CD, Laumann TO, Kandala S, Hong X, Repetitive transcranial magnetic stimulation with resting-state network targeting for treatment-resistant depression in traumatic brain injury: A randomized, controlled, double-blinded pilot study. J Neurotrauma. 2019; 36(8): 1361– 1374. doi: 10.1089/neu.2018.5889 30381997 PMC6909726 · DOI · Paper page
  20. [22]George MS, Raman R, Benedek DM, Pelic CG, Grammer GG, Stokes KT A two-site pilot randomized 3 day trial of high dose left prefrontal repetitive transcranial magnetic stimulation (rTMS) for suicidal inpatients. Brain Stimul. 2014; 7(3): 421– 431. doi: 10.1016/j.brs.2014.03.006 24731434 · DOI · Paper page
  21. [23]Hoy KE, McQueen S, Elliot D, Herring SE, Maller JJ, Fitzgerald PB. A pilot investigation of repetitive transcranial magnetic stimulation for post-traumatic brain injury depression: Safety, tolerability, and efficacy. J Neurotrauma. 2019; 36(13): 2092– 2098. doi: 10.1089/neu.2018.6097 30712461 · DOI
  22. [25]Oberman LM, Exley S, Philip NS, Siddiqi SH, Adamson MM, Brody DL. Use of repetitive transcranial magnetic stimulation in the treatment of neuropsychiatric and neurocognitive symptoms associated with concussion in military populations. J Head Trauma Rehabil. 2020; 35(6): 388– 400. doi: 10.1097/HTR.0000000000000628 33165152 PMC7664843 · DOI · Paper page
  23. [26]Tsai PY, Chen YC, Wang JY, Chung KH, Lai CH. Effect of repetitive transcranial magnetic stimulation on depression and cognition in individuals with traumatic brain injury: A systematic review and meta-analysis. Sci Rep. 2021; 11(1): 16940. doi: 10.1038/s41598-021-95838-2 34417481 PMC8379199 · DOI
  24. [27]Mollica A, Safavifar F, Fralick M, Giacobbe P, Lipsman N, Burke MJ. Transcranial magnetic stimulation for the treatment of concussion: A systematic review. Neuromodulation. 2021; 24(5): 803– 812. doi: 10.1111/ner.13319 33184973 · DOI
  25. [28]Sydnor VJ, Bouix S, Pasternak O, Hartl E, Levin-Gleba L, Reid B, Mild traumatic brain injury impacts associations between limbic system microstructure and post-traumatic stress disorder symptomatology. Neuroimage Clin. 2020; 26:102190. doi: 10.1016/j.nicl.2020.102190 PMC7026283 32070813 · DOI
  26. [29]Liston C, Chen AC, Zebley BD, Zebley B, Drysdale AT, Gordon R, Default mode network mechanisms of transcranial magnetic stimulation in depression. Biol Psychiatry. 2014; 76(7): 517– 526. doi: 10.1016/j.biopsych.2014.01.023 24629537 PMC4209727 · DOI · Paper page
  27. [30]Philip NS, Barredo J, Aiken E, Carpenter LL. Neuroimaging mechanisms of therapeutic transcranial magnetic stimulation for major depressive disorder. Biol Psychiatry Cogn Neurosci Neuroimaging. 2018; 3(3): 211– 222. doi: 10.1016/j.bpsc.2017.10.007 29486862 PMC5856477 · DOI
  28. [31]Kozel FA, Johnson KA, Nahas Z, Nakonezny PA, Morgan PS, Anderson BS, Fractional anisotropy changes after several weeks of daily left high-frequency repetitive transcranial magnetic stimulation of the prefrontal cortex to treat major depression. J ECT. 2011; 27(1): 5– 10. doi: 10.1097/YCT.0b013e3181e6317d 20559144 PMC2975808 · DOI
  29. [32]Barredo J, Bellone JA, Edwards M, Carpenter LL, Correia S, Philip NS. White matter integrity and functional predictors of response to repetitive transcranial magnetic stimulation for posttraumatic stress disorder and major depression. Depress Anxiety. 2019; 36(11): 1047– 1057. doi: 10.1002/da.22952 31475432 PMC8015421 · DOI
  30. [34]Blevins CA, Weathers FW, Davis MT, Witte TK, Domino JL. The posttraumatic stress disorder checklist for DSM-5 (PCL-5): Development and initial psychometric evaluation. J Trauma Stress. 2015; 28(6): 489– 498. doi: 10.1002/jts.22059 26606250 · DOI · Paper page
  31. [36]Yesavage JA, Fairchild JK, Mi Z, Biswas K, Davis-Karim A, Phibbs CS,... & VA Cooperative Studies Program Study Team. (2018). Effect of repetitive transcranial magnetic stimulation on treatment-resistant major depression in US veterans: a randomized clinical trial. JAMA psychiatry, 75(9), 884– 893. doi: 10.1001/jamapsychiatry.2018.1483 29955803 PMC6142912 · DOI
  32. [37]Vasterling JJ, Aslan M, Lee LO, Proctor SP, Ko J, Jacob S, Concato J. Longitudinal associations among posttraumatic stress disorder symptoms, traumatic brain injury, and neurocognitive functioning in army soldiers deployed to the Iraq war. J Int Neuropsychol Soc. 2018; 24(4): 311– 323. doi: 10.1017/S1355617717001059 29199924 PMC6103787 · DOI
  33. [38]Sripada RK, Rauch SA, Tuerk PW, Smith E, Defever AM, Mayer RA, Mild traumatic brain injury and treatment response in prolonged exposure for PTSD. J Trauma Stress. 2013; 26(3): 369– 375. doi: 10.1002/jts.21813 23696427 · DOI
  34. [39]Herrold AA, Siddiqi SH, Livengood SL, Bender Pape TL, Higgins JP, Adamson MM, Customizing TMS Applications in Traumatic Brain Injury Using Neuroimaging. J Head Trauma Rehabil. 2020; 35(6): 401– 411. doi: 10.1097/HTR.0000000000000627 33165153 · DOI
  35. [40]Williams LM, Coman JT, Stetz PC, Walker NC, Kozel FA, George MS, Identifying response and predictive biomarkers for transcranial magnetic stimulation outcomes: Protocol and rationale for a mechanistic study of functional neuroimaging and behavioral biomarkers in veterans with Pharmacoresistant depression. BMC Psychiatry. 2021; 21(1): 35. doi: 10.1186/s12888-020-03030-z37 33435926 PMC7805238 · DOI

Authors
Philip, N. S., Ramanathan, D., Gamboa, B., Brennan, M. C., Kozel, F. A., Lazzeroni, L., & Madore, M. R.
Affiliations
  • Brown University (US)
  • University of California San Diego (US)
  • VA Palo Alto Health Care System (US)
  • Florida State University (US)
Corresponding author
Madore, Michelle R.
ORCID
Venue
Neuromodulation: Technology at the Neural Interface
Publisher
Elsevier BV
Published
2023-06
Volume
26
Issue
4
Pages
878-884
ISSN
1094-7159 (ISSN-L)
DOI
10.1016/j.neurom.2022.11.015
PMC
PMC10765323
OpenAlex
W4318767338
Cited by
21
References
40
Citations by year
2026: 6 · 2025: 6 · 2024: 8 · 2023: 1
FWCI
2.16
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuromodulation Technology at the Neural Interface (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • U.S. Department of Veterans Affairs (I01CX002088, I50RX002864)
  • National Institutes of Health
  • National Institute of Mental Health (R01MH120126, MH120126)
Topics
  • Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
  • Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
  • Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
Keywords
repetitive transcranial magnetic stimulation, mild traumatic brain injury, major depressive disorder, post-traumatic stress disorder, veterans, traumatic brain injury, treatment response, comorbidities, PCL-5, Patient Health Questionnaire
MeSH terms
Brain Injuries, Traumatic, Brain Concussion, Depression, Depressive Disorder, Major, Major Depressive Disorder, Humans, Retrospective Studies, Stress Disorders, Post-Traumatic, Veterans, Transcranial Magnetic Stimulation

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review