EEG-Guided Transcranial Magnetic Stimulation for Adults With Depression

This is a randomized, double-blind, 3 arm trial with a parallel design. All patients will receive an FDA cleared form of TMS called intermittent theta burst (iTBS) but will be randomized to 1) Closed-loop TMS-EEG with stimulation bursts delivered at the trough of theta waves, 2) Closed- loop TMS-EEG with stimulation bursts delivered at the peak of theta waves or 3) Closed-loop TMS-EEG random phase TMS delivery (control stimulation). Patients in all 3 study arms will wear EEG caps and undergo similar procedures to facilitate blinding. Blinded clinical raters will collect depression symptom severity measures at screening, baseline, and weekly for 6 weeks followed by monthly follow-up visits for 3 months to assess for delayed responses to treatment. The iTBS will be delivered with a MagVenture Cool B70 coil and X100 stimulator. TBS treatment will be delivered once daily (5 days per week for 6 weeks) to the left DLPFC at 120% MT, 600 pulses per session. The Localite system will provide neuronavigation for treatment site localization with the participant's structural MRI or in patients that cannot obtain an MRI, the provided standard MNI atlas. Depressive symptom severity will be assessed weekly with the 17-item Hamilton Depression Rating Scale (HDRS), the Montgomery-Asberg Depression Rating Scale (MADRS), a patient-reported Patient Health Questionnaire (PHQ-9)55, and a Generalized Anxiety Disorder 7-time scale (GAD-7)56. Patients will continue to receive any standard clinical psychotherapy at the same frequency and will continue current psychotropic medications at the current dose consistently for the duration of the study. Clinical assessments visits will take place during the last treatment day (treatment 5) of every week for 6 weeks of treatment. Follow-up assessments will be collected in person or remotely (via zoom or telephone appointment) based on patient preference.