Reward circuitry predicts the effects of fMRI-guided accelerated prolonged iTBS in treatment-resistant depression

Transcranial magnetic stimulation (TMS) offers a noninvasive alternative to pharmacotherapy for treatment-resistant depression (TRD). A new fMRI-guided accelerated TMS protocol demonstrates rapid clinical efficacy, although predictive biomarkers of response have not yet been established. This study examines the efficacy of the new TMS protocol in a unique clinical setting and explores a biomarker for predicting antidepressant response to accelerated intermittent theta burst stimulation (iTBS).

We conducted a retrospective chart review of 29 patients (ages 18-74) who received accelerated iTBS targeting the left dorsolateral prefrontal cortex (DLPFC). Patients received 10 iTBS sessions per day for 5 consecutive days, totaling 50 sessions. Depressive symptoms were assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) throughout the treatment. Resting-state fMRI data was used to conduct correlational analysis between the mesolimbic pathway and clinical improvement.

Patients exhibited a rapid and significant reduction in MADRS scores, with response and remission rates of 72.41% and 65.52%, respectively, by Day 5. Suicidality significantly improved from baseline to Day 5, with 86% of patients having a resolution of suicidality by Day 5. Resting state functional connectivity (RSFC) between the right NAcc and left VTA was significantly associated with greater percent reduction in depressive symptoms.

Our findings suggest that accelerated iTBS yields rapid antidepressant effects and robust reductions in suicidality in treating TRD. Moreover, RSFC within the mesolimbic pathway may serve as a potential biomarker for predicting treatment response. Future work should conduct double-blind, sham-controlled trials with larger samples.