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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, 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]
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“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]
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“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
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“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
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“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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Self-citation
Metadata
- 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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