Theta-Burst Transcranial Magnetic Stimulation for Posttraumatic Stress Disorder
Open accessAbstract
OBJECTIVE: Posttraumatic stress disorder (PTSD) is a highly prevalent psychiatric disorder associated with disruption in social and occupational function. Transcranial magnetic stimulation (TMS) represents a novel approach to PTSD, and intermittent theta-burst stimulation (iTBS) is a new, more rapid administration protocol with data supporting efficacy in depression. The authors conducted a sham-controlled study of iTBS for PTSD. METHODS: Fifty veterans with PTSD received 10 days of sham-controlled iTBS (1,800 pulses/day), followed by 10 unblinded sessions. Primary outcome measures included acceptability (retention rates), changes in PTSD symptoms (clinician- and self-rated), quality of life, social and occupational function, and depression, obtained at the end of 2 weeks; analysis of variance was used to compare active with sham stimulation. Secondary outcomes were evaluated 1 month after treatment, using mixed-model analyses. Resting-state functional MRI was acquired at pretreatment baseline on an eligible subset of participants (N=26) to identify response predictors. RESULTS: Retention was high, side effects were consistent with standard TMS, and blinding was successful. At 2 weeks, active iTBS was significantly associated with improved social and occupational function (Cohen's d=0.39); depression was improved with iTBS compared with the sham treatment (d=-0.45), but the difference fell short of significance, and moderate nonsignificant effect sizes were observed on self-reported PTSD symptoms (d=-0.34). One-month outcomes, which incorporated data from the unblinded phase of the study, indicated superiority of active iTBS on clinician- and self-rated PTSD symptoms (d=-0.74 and -0.63, respectively), depression (d=-0.47), and social and occupational function (d=0.93) (all significant). Neuroimaging indicated that clinical improvement was significantly predicted by stronger (greater positive) connectivity within the default mode network and by anticorrelated (greater negative) cross-network connectivity. CONCLUSIONS: iTBS appears to be a promising new treatment for PTSD. Most clinical improvements from stimulation occurred early, which suggests a need for further investigation of optimal iTBS time course and duration. Consistent with previous neuroimaging studies of TMS, default mode network connectivity played an important role in response prediction.
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Assuming a significance level of 0.05, a mean SOFAS score of 44.6, and a SD of 15, with 50 veterans, the study will have 82% power to detect a significant interaction between time and treatment assuming no change over time in the sham-iTBS group and a change of 13 points in the active iTBS group.
“Assuming a significance level of 0.05, a mean SOFAS score of 44.6, and a SD of 15, with 50 veterans, we will have 82% power to detect a significant interaction between time and treatment assuming no change over time in the sham-iTBS group and a change of 13 points in the active iTBS group [90].”
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 [90]
Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredOther studies have found meaningful change in both the UPPS-P and SOFAS over a 2-week neuromodulation intervention period among individuals with major depression.
“Other studies have specifically found meaningful change in both the UPPS-P and SOFAS over a 2-week neuromodulation intervention period among individuals with major depression [90,135].”
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 [90]
The Results (Clinical Outcomes; page not provided) report significant SOFAS improvement after two weeks of active stimulation. The paper does not report UPPS-P change. Its Methods identify chronic PTSD as the principal inclusion criterion, although the Results say 90% of participants had comorbid depression; it therefore does not establish the stated finding in a study of individuals recruited for major depression. (LLM, conf=0.90)
Experimental — accuracy not yet measuredRandomised and naturalistic studies suggest that rTMS and theta-burst stimulation may reduce PTSD symptoms.
“Randomised and naturalistic studies suggest that rtMs and theta-burst stimulation may reduce PtsD symptoms”
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 Philip et al. 2019
The Introduction says existing data suggest TMS is effective for PTSD, and the Results report reduced PTSD symptoms after intermittent theta-burst stimulation in a randomized study, particularly at one month after an unblinded treatment phase. Our copy does not identify a naturalistic study or establish that naturalistic studies support the claim. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThis cluster-specific pattern is consistent with neurobiological models implicating prefrontal-limbic regulation of arousal as a proximal mechanism of TMS effects in trauma-related populations, although the limited number of courses contributing to each cluster-level comparison (n ≈ 28 at Follow-up) reduces the precision of these estimates and warrants cautious interpretation.
“this cluster-specific pattern is consistent with neurobiological models implicating prefrontal-limbic regulation of arousal as a proximal mechanism of tMs effects in trauma-related populations, although the limited number of courses contributing to each cluster-level comparison (n ≈ 28 at Follow-up) reduces the precision of these estimates and warrants cautious interpretation (Petrosino et al. 202”
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 Philip et al. 2019
Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredAttrition rates are expected to be low, under 10%, based on similar studies of iTBS protocols for patients with depression and PTSD receiving treatment of similar duration.
“On the basis of similar studies of iTBS protocols for patients with depression and PTSD, receiving treatment of similar duration, attrition rates are expected to be low—under 10% [58,90,91].”
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- Authors
- Philip, N. S., Barredo, J., Aiken, E., Larson, V., Jones, R. N., Shea, M. T., Greenberg, B. D., & van ’t Wout-Frank, M.
- Affiliations
- Brown University (US)
- The Center for Neurorestoration and Neurotechnology, Providence VA Medical Center, and the Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, R.I.
- Corresponding author
- Philip, Noah S.
- ORCID
- Venue
- American Journal of Psychiatry
- Published
- 2019-11-01
- Volume
- 176
- Issue
- 11
- Pages
- 939-948
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC6824981
- OpenAlex
- W2955256995
- Cited by
- 183
- References
- 54
- Citations by year
- 2026: 23 · 2025: 28 · 2024: 33 · 2023: 22 · 2022: 22 · 2021: 25 · 2020: 24 · 2019: 6
- FWCI
- 8.47
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Veterans Affairs (IK2 CX001824, IK2 CX000724, I21 RX002032)
- Topics
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
- Keywords
- post-traumatic stress disorder, intermittent theta burst stimulation, transcranial magnetic stimulation, veterans, depression, quality of life, default mode network, resting-state functional connectivity, treatment response prediction, sham-controlled treatment
- MeSH terms
- Depression, Double-Blind Method, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Patient Acceptance of Health Care, Quality of Life, Social Behavior, Stress Disorders, Post-Traumatic, Theta Rhythm, Treatment Outcome, Transcranial Magnetic Stimulation
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