Study Testing if Fast or Slow rTMS is Better for the Treatment of Posttraumatic Stress Disorder (PTSD)

Participants wishing to participate will contact the study team either personally or through their provider at the Veteran's request. Further means of recruitment are as follows. 1) Flyers will be placed at the University of South Florida and other high learning institutions in the local area. 2)The study team will provide flyers and give talks at Veteran associated organizations. 3)The study will also be advertised on the JAH Facebook page as well as the JAH Twitter account. 4) Veterans with a PTSD diagnosis will be identified using the VSSC web reports. Using this method, the study staff will pre-screen the CPRS records of 5,000 veterans to identify potential subjects. The identified veterans will be sent a recruitment letter with detailed information about the study as well as a copy of the informed consent. After a 10-day waiting period, the study team will them contact the veteran by phone to see if they are interested in participating. The study team will review the Veteran's medical record and discuss the study and its entry criteria with the participants and/or provider. Those suitable to enter the trial and interested will be scheduled for a screening/baseline visit. These participants will typically be those who have either failed or are not willing to engage in standard evidence-based psychotherapy.

The screening/baseline visit will begin by acquiring written informed consent. Subsequently, evaluations to determine safety and appropriateness, as well as clinical ratings and laboratory testing (UDS and urine pregnancy testing) will be performed. Those deemed eligible will be randomized to 1 Hz versus 10 Hz stratified by significant depression (MADRS > 19) and treated on a subsequent day within a week. Participants will be treated for 5 days a week for 6 weeks with a 3-week taper (3 per week for 1 week, 2 per week for 1 week, 1 per week for 1 week). Participants will undergo clinical evaluation weekly for clinical effect during the treatment, at the end of the taper (or when participant chooses to leave the trial) and at 1- and 3-months post treatment. In addition, safety will be assessed prior to each treatment. The total time in study for a participant will be approximately 22 weeks.

Randomization will be stratified based on significant depressive symptoms which will be defined as a MADRS score > 19 versus MADRS score ≤ 19. Using a computer randomization schedule, an investigator not involved directly with the trial will generate two random lists of active and sham cards that will be placed in envelopes. The two groups will be MADRS score > 19 versus MADRS score ≤ 19. When the participant is ready to begin the first treatment, the treater will pull the next envelope in line for the appropriate group and open the envelope to determine the randomization assignment. The participant will know the assignment as well as the treater but the investigator doing all the clinician rating scales will be masked to assignment.

Medications and other treatments: Participants will be allowed to continue current medications and therapy as long as does not increase risk of rTMS and is held constant during the six weeks of the trial. Doses may be adjusted as need for side effects.

Materials obtained for research purposes include demographic information, contact information (for purposes of the study only), medical/psychiatric history (from interviews/ questionnaires), cognitive test data, laboratory data, and clinical data. All of the data will be obtained for research purposes.

Treatment with the Neurostar (Repetitive Transcranial Magnetic Stimulation) Stimulation System may involve other risks that are not known at the present time. The long-term effects of rTMS (Repetitive Transcranial Magnetic Stimulation) are not known. Legal and social risks of participation in this research are unknown.

The PI will monitor the safety of the participants to continue in the trial. The PI will be seeing the participants in person typically on at least a weekly basis. The PI will review the study data for side effects on an ongoing basis but more formally every 12 months to ensure no trends in the data of increased risk.

The data will only be used by the research team within the VA to address the research questions.

Inclusion criteria

• Male and female veteran outpatients aged 18-50 years old
• Meet DSM-IV criteria for PTSD as determined by clinical interview and CAPS for DSM-5
• A PTSD checklist - (PCL) ≥ 45 at Screening/Baseline
• On stable medication and/or psychotherapy for 1 month and clinically appropriate to maintain for duration of trial
• Clinically competent to give informed written consent

Exclusion criteria

• Veterans currently enrolled in an acute treatment of PTSD using evidence based psychotherapy including Prolonged Exposure Therapy (PE), Cognitive Processing Therapy (CPT), or Eye Movement Desensitization and Reprocessing (EMDR)
• History of epilepsy or seizure disorder, mass brain lesions, cerebrovascular accident, metal in the skull, a history of major head trauma defined as greater than mild TBI, or any neurologic condition likely to increase risk of rTMS.
• Suicidal risk that precludes safe participation defined as clinical impression that the subject is at significant risk for suicide.
• Lifetime history of schizophrenia, schizoaffective, or other psychotic disorder, bipolar disorder type I or II, dementia, dissociative disorders, or sexual and gender identity disorder
• Personality disorder that makes participation in the trial difficult
• History of problematic Substance Use Disorder in the last 3 months except nicotine and caffeine
• Taking any medication that significantly lowers the seizure threshold (e.g., stimulants, theophylline, first generation antipsychotics, etc.)
• Unstable medical conditions that precludes safe participation in rTMS treatment trial
• Known or suspected pregnancy
• Nursing mothers
• Women of child-bearing potential not using medically accepted form of contraception when engaged in sexual intercourse
• Any metal or device implants that would increase risk of rTMS
• Unable to determine the motor threshold in the subject
• History of Vagus Nerve Stimulation or Electroconvulsive Therapy
• Currently in another investigational study