Veterans with posttraumatic stress disorder (PTSD) need more effective treatments. Existing options can have limited adherence and can be very time-consuming. As such, alternative interventions are needed. Transcranial magnetic stimulation (TMS) has been FDA-cleared for depression since 2008 and has recently been cleared to treat smoking cessation and obsessive-compulsive disorder. It has demonstrated promise for reducing PTSD symptom severity but standard TMS has a significant time requirement. This study will compare an accelerated 5-day form of TMS versus sham for PTSD, characterizing efficacy and durability. This project will provide important information that can be implemented in the near term for Veterans with PTSD.

The primary research question of the proposed study is: Can transcranial magnetic stimulation (TMS) effectively treat posttraumatic stress disorder in Veterans using a pragmatic accelerated approach? The investigators address the need to improve symptom severity in this population utilizing the RAPID5 TMS protocol which delivers five treatments per day over the course of five days. The proposed four-year randomized controlled trial will compare the RAPID5 protocol to a Sham TMS Control Condition. The primary aim of the proposed research is to evaluate the efficacy of TMS to ameliorate PTSD symptoms in Veterans. The second aim is to examine the durability of PTSD symptom reduction resultant from the RAPID5 protocol. Given the high rate of mild traumatic brain injury (mTBI) among Veterans with PTSD, the exploratory aims of the proposed research seek to assess the contribution of mTBI in the context of PTSD on TMS outcomes.

Exploratory aims of the proposed research are: 1) examine whether mTBI status moderates PTSD symptom reduction, 2) assess whether differences in executive functioning moderate or mediate PTSD symptom reduction in Veterans with and without mTBI, and 3) will RAPID5 result in improved executive functioning in Veterans with PTSD.

These aims will be testing in a double-blind randomized controlled trial which will compare the efficacy of RAPID5 to sham TMS. This trial will include 90 Veterans meeting criteria for PTSD ages 18-70 with half randomized to RAPID5 and half randomized to sham TMS. For the RAPID5 condition, Veterans will receive five treatments per day for five consecutive business days. This protocol is based on evidence from previous work in depression and pilot data collected within the national Clinical TMS Program. Veterans randomized to the sham control condition will receive five treatments per day for five consecutive business days. After completion of the active treatment phase, Veterans will be assessed at two follow-up timepoints: 1 month and 3 months posttreatment.

Participants will complete several assessments, including but not limited to semi-structured clinical interviews, symptom self-report rating measures, quality of life measures, and neuropsychological measures assessing executive functioning. The goal is to provide evidence of the efficacy of an accelerated TMS treatment protocol in reducing PTSD symptom severity, resulting in an easily implementable VA healthcare systemwide implementation of this protocol across the VA enterprise.

Inclusion Criteria:

• Diagnosis of chronic PTSD, meeting DSM-5 criteria.
• Eligible Veterans (regardless of sex) will be between the ages of 18-70.
• Symptomatic despite ongoing stable treatment (medications, psychotherapy, etc.) for at least 6 weeks before study procedures.
• Ongoing medications and psychotherapy will be allowed to continue unchanged during the study.
• For safety, participants must meet established screening criteria for magnetic resonance imaging (MRI). This is implemented as a conservative measure given the novel application of TBS in this population since MRI involves magnetic fields at a similar intensity to those emitted from the stimulation coil. These measures require a patient not to have the following (unless MRI-safe): A cardiac pacemaker, implanted device (deep brain stimulation) or metal in the brain, cervical spinal cord, or upper thoracic spinal cord.
• Willingness to participate in a clinical trial for approximately 4 to 6 months (consisting of a treatment phase with a 4-month follow-up period).
• Veterans must also be willing and able to comply with all study-related procedures and visits and be capable of independently reading and understanding information materials and providing written informed consent.
• Sufficient visual and auditory acuity to allow neuropsychological testing.

Exclusion Criteria:

Psychiatric Exclusions

• Primary psychotic disorder, bipolar I disorder, and greater than moderate substance use disorder (within the last month, excluding nicotine/caffeine, assessed by a urine drug screen as indicated), determined by the Mini International Neuropsychiatric Interview (MINI).
• Active suicidal intent or plan, as detected on screening instruments or in the investigator team's opinion, is likely to attempt suicide within 6 months.
• The presence of any other condition or circumstance that, in the opinion of the investigator team, has the potential to prevent study completion and/or to have a confounding effect on outcome assessments.

Medical Exclusions

• History of neurological disorder (e.g., multiple sclerosis, seizure disorder, etc.) or systemic illness affecting CNS function (e.g., liver failure, kidney failure, congestive heart failure, metastatic cancer) or that could meaningfully impact cortical excitability.
• Acute illness or unstable chronic illness, e.g., history of severe liver disease (cirrhosis, esophageal varices, ascites, portal hypertension, hepatic encephalopathy).
• Pregnant or breastfeeding and planning to become pregnant within the next 3 months.
• Have a mass lesion, cerebral infarct, or other neuroanatomical abnormality located at the TMS treatment site (DLPFC); a lifetime history of a) seizure disorder b) primary or secondary CNS tumors c) stroke or d) cerebral aneurysm.
• Greater than mild traumatic brain injury (following VA/DoD definitions).
• Inability to read, unable to verbalize understanding, and voluntarily sign the Informed Consent.