Accelerated Intermittent Theta Burst in Treatment-Naive Adolescents

This single-site open-label clinical trial aims to test the safety and efficacy of the Magnus Neuromodulation System (MNS) with Stanford Accelerated Intermittent Neuromodulation Therapy (SAINT®) technology in treatment-naive adolescents with major depressive disorder (MDD) who remain antidepressant-free throughout the treatment. The SAINT® protocol, or a truncated version (5 or 10 applications per day to a customized target within the left dorsolateral prefrontal cortex \[L-DLPFC\] identified with fMRI for five consecutive days), in combination with MNS software will be delivered to each adolescent participant. Changes in depressive symptoms will be measured at baseline and two follow up visits. Additionally, parents and adolescents will answer questions regarding their preference for SAINT® as a first-line treatment option for MDD. The hypothesis is that adolescent participants receiving SAINT® or the truncated version will demonstrate similar response and remission rates that are comparable to SAINT® trials in adults (80-90%) as measured by the Childhood Depression Rating Scale (CDRS) and Hamilton Depression Rating Scale. The primary objective of this study is to determine the efficacy of active SAINT® in reducing symptoms of depression as measured by the CDRS at the one-month follow up time point. The study will enroll approximately 40 participants and employ a two-arm design with 20 participants per arm. The target population is adolescents of all genders and ethnicities who are between 14 and 19 years of age with a diagnosis of MDD experiencing their first major depressive episode who have not received a full course of prior treatment and who are otherwise in good general health. Participants must be without contraindications to Magnetic Resonance Imaging (MRI) or transcranial magnetic stimulation (TMS) and must be able to attend all study visits. This study will deliver SAINT® via a MagPro X100 edition (MagVenture, Skovlunde, Denmark) TMS device equipped with a Cool-B65 A/P coil. The stimulation paradigm consists of 5 or 10 daily sessions (25 or 50 total over 5-days) of SAINT® (3-pulse 50-Hz bursts at 5-Hz for 2-second trains, with trains every 10 seconds) guided by MNS, delivered with 50-minute inter-session intervals (10-minute sessions, 50-minutes in between sessions). Stimulation will be delivered at 90% of the resting motor threshold (with depth correction to account for the distance between the scalp and cortex).