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.

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.

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

Participants will be randomized to receive either 1) active aTMS at their individualized target or 2) sham aTMS at their individualized target in a 2:1 randomization. One research assistant (RA) is the only individual unblinded in this study. The unblinded RA will have no other interactions with participants. RAs delivering treatment with stimulate participants with sham or active aTMS, with randomization assigned by the unblinded RA. Blind will be broken at 1-month follow-up visit for all participants, physicians, and treating technicians.