Transcranial magnetic stimulation in us military veterans-a naturalistic study in the veterans health administration

Background: Repetitive transcranial magnetic stimulation (rTMS, hereafter TMS) has emerged as evidence-based treatment for pharmacoresistant major depressive disorder (MDD) and has been cleared by the US Food and Drug Administration for over a decade In that time, data has emerged supporting the use of TMS utilizing different devices, settings, and patient populations One particular patient population of interest in the US are military Veterans;this patient group is thought to have generally higher levels of medical and psychiatric comorbidity, as well as elevated risk for suicide A recent negative study of TMS indicated that active stimulation did not separate from sham, and poor response was particularly prevalent in Veterans who had comorbid posttraumatic stress disorder Yet, other studies have consistently indicated efficacy of TMS for Veterans including with PTSD in other studies To this end, the VA instituted a nationwide rollout of TMS, with the purpose to evaluate clinical outcomes in naturalistic settings and thus inform real-world practice This abstract reports clinical outcomes of the first cohort of patients to receive TMS at the VA as part of this program, where we hypothesized that TMS would be safe, well tolerated, and provide clinically meaningful reductions in depressive symptoms as well as comorbid PTSD symptoms Methods: VA Palo Alto Healthcare System Mental Illness Research Education and Clinical Center served as the central coordinating site for this naturalistic study;the VA Palo Alto/ Stanford Institutional Review Board approved procedures related to this report Individual sites received training through the coordinating site and data gathered through a centralized VA REDCap database Veterans were eligible for TMS if they met standard inclusion/clearance criteria for TMS (e g , failure of at least one antidepressant in the current major depressive episode, etc );in general other treatments were unchanged for approximately six weeks before stimulation, and remained unchanged during stimulation, although this could be modified depending on a Veteran's clinical situation TMS parameters were at local clinical discretion, and generally were high frequency stimulation (10Hz or intermittent theta burst) delivered to the left dorsolateral prefrontal cortex at 120% of motor threshold over 6-8 weeks Depression and PTSD symptoms were measured using the 9-item patient health questionnaire (PHQ9) and PTSD symptom checklist for DSM5 (PCL-5);outcomes of interest included mean changes in both rating scales, as well as dichotomous outcomes describing response (>50% reduction) and remission (score10 points) and those no longer meeting threshold criteria for PTSD (score <33) on the PCL-5 Safety outcomes were measured through database queries and separate inquiries across the sites Outcomes were analyzed using paired-sample t-tests and missing data were addressed using multiple imputations This report includes all Veterans that received TMS up until March 2020 (i e , pre-COVID) Results: The cohort included N=413 Veterans with major depression 380 (92%) reported some degree of PTSD symptoms, and 275 (66 6%) had threshold-level PTSD symptoms Average age was 51 years (SD = 14 14, range 22 - 89), and 74 2 % identified as male The majority of Veterans were treated with high frequency stimulation to the left dorsolateral prefrontal cortex There was a significant decrease in self-reported depression symptoms on the PHQ9 (t(412) = 24 15, p < 0 01;pre-TMS: mean = 18 2, standard deviation = 5 06, post-TMS: mean = 10 66, standard deviation = 7 12) Depression response and remission rates were 46 2% (n=191) and 23 7% (n=98), respectively There was also a significant decrease on self-reported PTSD symptoms on the PCL-5 (t(379) = 18 85, p < 0 01;pre-TMS : mean = 43 80 SD = 18 36, post-TMS: M = 28 15, SD = 20 42) Of the Veterans with threshold-level PTSD symptoms at baseline, n=159 (57 5%) demonstrated clinically meaningful reduction and n=130 (47 2%) no longer met PTSD threshold criteria post-treatment TMS was generally safe as delivered;four Veterans experienced unexpected side effects requiring significant medical intervention One Veteran reportedly had a seizure (H-coil), and five were hospitalized for worsened psychiatric symptoms Conclusions: This data represents the first multisite naturalistic study of TMS for Veterans with pharmacoresistant major depression Consistent with this patient population, the majority reported comorbid MDD & PTSD TMS resulted in statistically significant and clinically meaningful improvements in depressive and PTSD symptoms Stimulation was safe as provided, with side effects consistent with the known profile of TMS Limitations include those inherent to naturalistic cohort studies Furthermore, all Veterans were engaged in concurrent clinical care, and we did not differentiate between different stimulation parameters Future reports, using the associated network of clinical sites, will focus on key related questions including evaluating the impact of different TMS parameters or approaches, as well as the study of biological outcomes such as functional magnetic resonance imaging and electroencephalography to better identify biomarkers of treatment response in this population Caveats notwithstanding, this is the largest report of TMS in Veterans and provides a clear indication of efficacy and safety in real-world environments