Heart rate deceleration tracks antidepressant response to accelerated dorsomedial prefrontal intermittent theta-burst stimulation in major depression

Identifying accessible, low-cost biomarkers of treatment response remains a key challenge in personalizing transcranial magnetic stimulation (TMS) therapy for major depressive disorder (MDD). We tested whether stimulation-evoked heart rate deceleration (HRD) predicts antidepressant response to accelerated intermittent theta-burst stimulation (iTBS) of the dorsomedial prefrontal cortex (dmPFC). Thirty-two patients with MDD received accelerated bilateral dmPFC-iTBS delivered with a double-cone coil. Heart rate was sampled continuously at 1-second intervals using a low-cost chest-strap sensor, and HRD was quantified as the relative change from a 1-minute pre-stimulation baseline to the mean heart rate across the stimulation window. Response was defined as a 50% or greater reduction in 17-item Hamilton Depression Rating Scale score. Response and remission rates were 65.6% and 56.3%, respectively. Responders showed greater HRD than non-responders (Cohen’s d = 1.40). HRD discriminated responders with an area under the curve of 0.905; a 2% cutoff yielded 90.5% sensitivity and 81.8% specificity. Each 1% increase in HRD was associated with approximately 2.5-fold higher odds of response. Stimulation-evoked HRD tracked antidepressant response and is compatible with modulation of a prefrontal-autonomic network; it warrants evaluation in larger sham-controlled studies as a pragmatic, bedside-accessible candidate marker of response. The trial was registered retrospectively at ClinicalTrials.gov (identifier NCT07615387 first posted 29/05/2026).