Targeted Accelerated TMS for Post-Traumatic Stress Disorder (TAP)

Post-traumatic stress disorder (PTSD) is a highly prevalent and debilitating condition among veterans and active-duty military personnel, with rates as high as 30% in certain combat-exposed populations. Conventional treatments such as prolonged exposure therapy and pharmacotherapy have limited efficacy and high dropout rates, highlighting the need for novel, rapidly effective interventions.

Transcranial magnetic stimulation (TMS) has been well established for treatment-resistant depression (TRD). Traditional TMS, which involves 6 to 7 weeks of daily, weekday scalp-targeted treatment, shows open-label response and remission rates of 58.1% and 30%, respectively. However, such protocols may be impractical for military personnel with limited medical leave. A new form of accelerated TMS (aTMS) that involves 10 imaging-guided treatments per day for 5 consecutive days has demonstrated substantial antidepressant benefits within days and response rates of 69% at 1-month follow-up. This protocol has not been tested for PTSD, in part because there was no causally informed brain circuit target. In this study, the investigators will test aTMS for PTSD using a novel PTSD circuit that the investigators have derived.

Study Overview

• Status: Recruiting
• Conditions: Post Traumatic Stress Disorder (PTSD)
• Intervention / Treatment: Procedure: Transcranial Magnetic Stimulation

Detailed Description

In a recent study in Nature Neuroscience, the investigators analyzed three independent datasets to derive a brain circuit causally linked to PTSD in military veterans. Investigators found that brain lesions that reduce the probability of developing PTSD (n=193) were connected to the same brain circuit based on the functional connectivity profiles of individual patients with PTSD using fMRI (n=180). Finally, investigators demonstrated that scalp-targeted TMS to our circuit rapidly improved PTSD symptoms (n=20).

Separately, the investigators partnered with a private clinic to administer open-label, circuit-targeted aTMS to patients with PTSD (n=8). Investigators found that the treatment was safe and tolerable. Response and remission rates were 75% and 63%, respectively. Of note, these response and remission rates assess outcomes up to 4 weeks after the treatment ends. This approach captures individual variability in response trajectory and aligns with our own data from aTMS treatment of TRD.

The strength of these findings has inspired us to launch a pilot randomized controlled aTMS trial in which the investigators prospectively target our PTSD circuit using each patient's neuroimaging data in combination with the accelerated TMS treatment protocol.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Interventional Psychiatry Research Group; Phone Number: 6175253526; Email: bwhtap@mgb.org

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• Age 18-65
• DSM-5 diagnosis of PTSD per PTSD Checklist for DSM-5 (CAPS-5)
• At least moderate symptoms of PTSD per PCL-5 (≥21)
• English proficiency sufficient to understand risks/benefits
• No new medications or medication increases before, during, or after aTMS
• Primary clinician (e.g. psychiatrist, therapist, psychologist, APRN, PA, etc.) responsible for psychiatric care before, during, and after the trial
• Agreement to lifestyle considerations:
• Abstain from becoming pregnant from screening to one-month after treatment (the MRI visit)
• Continue usual intake patterns of caffeine- or xanthine-containing products (e.g. coffee, tea, soft drinks, chocolate) throughout treatment
• No changes to routine intake of alcohol, tobacco, and recreational drugs if patients are using them at baseline for at least 24 hours before the start of each MRI and TMS session

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active aiTBS; Participants in this group will receive active aiTBS with neuronavigation to a treatment target identified with individualized resting state functional connectivity.	Procedure: Transcranial Magnetic Stimulation; Transcranial magnetic stimulation (TMS) is a focal, non-invasive form of brain stimulation that has FDA clearance for depression. In this study, a form of TMS called accelerated intermittent theta burst stimulation (aiTBS) will be administered under the supervision of a physician with TMS expertise.; Other Names: TMS; aiTBS; Accelerated intermittent theta burst stimulation
Sham Comparator: Sham aiTBS; Participants in this group will receive sham aiTBS with neuronavigation to a treatment target identified with individualized resting state functional connectivity. Participants in the sham group who continue to present with moderate PTSD symptoms (greater than or equal to 33 cutoff on PCL-5) at the post-treatment month 1 visit will be offered the opportunity to opt in and receive another course of active aTMS.	Procedure: Transcranial Magnetic Stimulation; Transcranial magnetic stimulation (TMS) is a focal, non-invasive form of brain stimulation that has FDA clearance for depression. In this study, a form of TMS called accelerated intermittent theta burst stimulation (aiTBS) will be administered under the supervision of a physician with TMS expertise.; Other Names: TMS; aiTBS; Accelerated intermittent theta burst stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PTSD Checklist with Criterion A for DSM-5 (PCL-5)	20 item PTSD scale, scored 0-80. Higher scores indicate worse symptoms. Investigators will use a repeated measures mixed model to examine the effect of treatment on PCL-5 scores over time as well as a group x time interaction not controlling for depression. Hypothesis: There will be a significant difference in PCL-5 score magnitude of change one month after treatment relative to baseline in the participants receiving active treatment vs. sham	Before treatment to 1-month post treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PTSD Checklist with Criterion A for DSM-5 (PCL-5)	20 item PTSD scale, scored 0-80. Higher scores indicate worse symptoms. Investigators will determine between-group effect size based on the change in PCL-5 score one month after treatment. Hypothesis: Relative to sham aTMS, active aTMS will show a moderate-to-large effect size.	Before treatment to 1-month post treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinician-Administered PTSD Scale for DSM-5 (CAP-5)	30-item clinical interview designed to assess PTSD based on DSM-5 criteria. Total scores from 0-80, with higher numbers indicating greater PTSD symptom severity.	Before treatment and 1 month after treatment
Clinically Useful Anxiety Outcome Scale (CUXOS)	20-item, self-report questionnaire that measures the severity of psychic and somatic anxiety symptoms. Scores range from 0-80, which higher scores indicating higher symptoms of anxiety.	Before treatment and daily for 5 treatment days
Beck Depression Inventory (BDI)	Depression severity rating scales (0-63, higher numbers indicate higher severity)	Before treatment, 1 week post treatment, and 1 month post treatment
Beck Anxiety Inventory (BAI)	Anxiety severity rating scale (0-63, higher numbers indicate higher severity)	Before treatment, 1 week post treatment, and 1 month post treatment
Young Mania Rating Scale (YMRS)	11 item scale evaluating mania. Scored 0-60. Higher score indicates worse outcome/higher mania	Before treatment, daily for 5 treatment days, and 1 month post treatment
Patient Global Impressions (PGI)	A single question assessing a patient's perception of their health or condition. Scores range from 1-7, one being the participant believes they are not at all ill, seven being an extremely ill individual.	Before and 1 month after treatment
Clinical Global Impression Scale (CGI)	Clinician-rated tool to assess the global severity of a patient's illness. 7-point scale from 1 (very much improved) to 7 (very much worse).	Before and 1 month after treatment
Adult Temperament Questionnaire	77-item self-report questionnaire assessing individuals temperament and personality. Scores range from 0-539, with scores in subsections of the questionnaire indicating various affects and temperaments.	Before treatment and 1 month after treatment
World Health Organization Disability Assessment Schedule II (WHODAS 2.0)	36-item functional assessment (each question rated 1-5) Minimum: 36 Maximum: 180 Can also be scored by percentiles Higher score indicates more disability	Before treatment and 1 month after treatment
World Health Organization Quality of Life (WHOQOL-BREF)	26-item questionnaire assessing an individual's perception of their quality of life (scores range from 0 to 100, where higher scores represent a better quality of life).	Before treatment and 1 month after treatment
Visual Analog Scale (Mood)	A single question asking participants to rate their current mood on a scale of 1-100 (higher scores indicate positive mood)	Before treatment and daily for 5 treatment days
Adult Attention Deficit/Hyperactivity Disorder Self-Report Scale (AARS)	ADHD rating scale (each question rated 1-5, higher scores indicate symptoms highly consistent with ADHD)	Before treatment and 1 month after treatment
Illness Intrusiveness Rating Scale (IIRS)	3 item scale measuring how illness affects function. Scored 13-91, higher score indicates higher illness intrusiveness severity	Before treatment and 1 month after treatment
McLean Screening Instrument for Borderline Personality Disorder (MS-BPD)	10-item questionnaire used to screen for BPD (scores range from 0 to 10; higher scores are associated with higher levels of/more severe BPD symptoms).	Before treatment and 1 month after treatment
Perceived Stress Scale (PSS)	Stress assessment scored 0-40, higher scores indicate higher stress	Before treatment and 1 month after treatment
Social Readjustment Rating Scale (SRRS)	A tool used to assess the potential stress associated with different life events (scores range from 0 to 430, with higher scores indicating higher levels of stress).	Before and 1 month after treatment
Pittsburgh sleep quality index (PSQI)	Self-report questionnaire to assess sleep quality, scored from 0 to 21. Higher scores indicate poorer sleep quality.	Before and 1 month after treatment

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: Mass General Home Base Program

Publications and helpful links

General Publications

• Cole EJ, Stimpson KH, Bentzley BS, Gulser M, Cherian K, Tischler C, Nejad R, Pankow H, Choi E, Aaron H, Espil FM, Pannu J, Xiao X, Duvio D, Solvason HB, Hawkins J, Guerra A, Jo B, Raj KS, Phillips AL, Barmak F, Bishop JH, Coetzee JP, DeBattista C, Keller J, Schatzberg AF, Sudheimer KD, Williams NR. Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression. Am J Psychiatry. 2020 Aug 1;177(8):716-726. doi: 10.1176/appi.ajp.2019.19070720. Epub 2020 Apr 7.
• Kessler RC, Sonnega A, Bromet E, Hughes M, Nelson CB. Posttraumatic stress disorder in the National Comorbidity Survey. Arch Gen Psychiatry. 1995 Dec;52(12):1048-60. doi: 10.1001/archpsyc.1995.03950240066012.
• Hoge CW, Castro CA, Messer SC, McGurk D, Cotting DI, Koffman RL. Combat duty in Iraq and Afghanistan, mental health problems, and barriers to care. N Engl J Med. 2004 Jul 1;351(1):13-22. doi: 10.1056/NEJMoa040603.
• Carpenter LL, Janicak PG, Aaronson ST, Boyadjis T, Brock DG, Cook IA, Dunner DL, Lanocha K, Solvason HB, Demitrack MA. Transcranial magnetic stimulation (TMS) for major depression: a multisite, naturalistic, observational study of acute treatment outcomes in clinical practice. Depress Anxiety. 2012 Jul;29(7):587-96. doi: 10.1002/da.21969. Epub 2012 Jun 11.
• Cole EJ, Phillips AL, Bentzley BS, Stimpson KH, Nejad R, Barmak F, Veerapal C, Khan N, Cherian K, Felber E, Brown R, Choi E, King S, Pankow H, Bishop JH, Azeez A, Coetzee J, Rapier R, Odenwald N, Carreon D, Hawkins J, Chang M, Keller J, Raj K, DeBattista C, Jo B, Espil FM, Schatzberg AF, Sudheimer KD, Williams NR. Stanford Neuromodulation Therapy (SNT): A Double-Blind Randomized Controlled Trial. Am J Psychiatry. 2022 Feb;179(2):132-141. doi: 10.1176/appi.ajp.2021.20101429. Epub 2021 Oct 29.
• Siddiqi SH, Philip NS, Palm ST, Carreon DM, Arulpragasam AR, Barredo J, Bouchard H, Ferguson MA, Grafman JH, Morey RA, Fox MD. A potential target for noninvasive neuromodulation of PTSD symptoms derived from focal brain lesions in veterans. Nat Neurosci. 2024 Nov;27(11):2231-2239. doi: 10.1038/s41593-024-01772-7. Epub 2024 Sep 24.

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2025
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: November 14, 2025
• First Submitted That Met QC Criteria: November 17, 2025
• First Posted (Actual): November 24, 2025

Study Record Updates

• Last Update Posted (Actual): February 2, 2026
• Last Update Submitted That Met QC Criteria: January 29, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: PTSD; Neuromodulation; TMS; Post traumatic stress disorder; Accelerated Transcranial Magnetic Stimulation
• Additional Relevant MeSH Terms: Trauma and Stressor Related Disorders; Mental Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Therapeutics; Magnetic Field Therapy; Transcranial Magnetic Stimulation
• Other Study ID Numbers: 2025P002359

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No