Heart Rate Metrics as Potential Biomarkers for Predicting Transcranial Magnetic Stimulation Treatment Response in Treatment-Resistant Depression

Repetitive transcranial magnetic stimulation (rTMS) is well-established for treating treatment-resistant depression (TRD). Given that depressive states are associated with alterations in heart rate (HR) dynamics, with emerging evidence suggesting that rTMS can modulate vagal activity, HR-derived indices might predict rTMS treatment response. To investigate whether early-session HR metrics could predict antidepressant efficacy of intermittent theta burst stimulation (iTBS), we conducted a clinical cohort study in Taipei, Taiwan (December 2023–May 2025). Depression severity was assessed at baseline and at completion of the iTBS treatment course using the Montgomery-Åsberg Depression Rating Scale (MADRS) and the 17-item Hamilton Depression Rating Scale (HAM-D17). Continuous HR data were recorded via fingertip photoplethysmography immediately before and during the earliest available iTBS session. Changes in HR metrics across multiple recording windows were calculated in relation to treatment response. Age- and sex-adjusted logistic regression and receiver operating characteristic (ROC) analysis were used to evaluate predictive performance and determine optimal cut-off values. Forty-three participants (31 females, 12 males; mean age 41.93 ± 13.07 years) were enrolled. Among eight HR indices, rTMS-induced low-frequency to high-frequency (LF/HF) power ratio change for the 15-60-second interval before and during stimulation demonstrated the strongest predictive performance for MADRS-defined treatment response (AUC = 0.82; 95% CI: 0.68–0.95; p < 0.001), with significance remaining after Bonferroni correction for addressing multiple comparisons. Early-session HR metrics, particularly changes in the LF/HF ratio, might work as promising biomarkers of iTBS treatment response, supporting the development of personalized rTMS treatment protocols.