Maintenance Individualized Neuromodulation and Depression-detection Via Sensors for Early Treatment

This proposal seeks to carry out a prospective, single-arm open label study aimed at sustaining treatment-resistant depression (TRD) response in patients with TRD who had responded to prior individualized resting-state functional connectivity (rs-FC)-guided intermittent theta burst stimulation (iTBS). It also seeks to detect and predict relapse risk by integrating rs-FC iTBS with a TMS-adapted needs-based symptom-titrated algorithm based longitudinal ECT (STABLE) maintenance scheduling algorithm, and passive digital biomarkers.

Inclusion Criteria: * Male/ female aged ≥ 21 to ≤ 70 years old * Able to give informed consent * Able to understand English * DSM-V diagnosis of current/ past major depressive disorder (MDD) episode * Non-response to an adequate trial (4 weeks) of at least 1 MDD medication as verified by a study clinician * Ability to comply with passive wearable use and weekly mobile assessments * Have previously completed a course of individualized, functional connectivity-guided accelerated iTBS and shown a clinical response (as defined by a ≥50% improvement in MADRS score against baseline, any time within 3 months following an acute iTBS course) * Able to comply with the full 12-month protocol inclusive of continuous digital monitoring Exclusion Criteria: * DSM-5 psychotic disorder * Drug or alcohol abuse or dependence (preceding 3 months) * Significant neurological disorder, which may pose increased risks with TMS, e.g., epilepsy * Metal in the cranium, skull defects, pacemaker, cochlear implant, medication infusion pump or any other electronic implants or devices * Tattoos containing ferromagnetic ink or permanent piercings * Pregnancy * Currently on multiple CNS stimulant medications (2 or more at maximal clinical doses) * Participant does not have the capacity to provide consent