The relationship between pre-treatment heart rate variability and response to low-frequency accelerated repetitive transcranial magnetic stimulation in major depression

Major depressive disorder (MDD) is now the first cause of disability worldwide. So far, no validated and scalable biomarker has been identified to help with response prediction to antidepressant treatment. Cardiac biomarkers such as heart rate variability (HRV) have been studied in MDD, but few studies have examined its potential use for outcome prediction to repetitive transcranial magnetic stimulation (rTMS). We recorded pre-treatment HRV in MDD participants prior to an rTMS course. We hypothesized that higher pre-treatment HRV would be correlated with better clinical outcomes. HRV was recorded as part of a single-arm, open-label rTMS feasibility study. Pre-treatment HRV was assessed in N = 30 MDD participants before they underwent a one-week (5 days, 8 daily sessions, 40 sessions total) accelerated rTMS (arTMS) course using a low-frequency 1 Hz course (600 pulses per session, 50-minute intersession interval) over the right dorsolateral prefrontal cortex at 120% of the resting motor threshold. Clinical outcomes were captured using the Beck Depression Inventory-II (BDI-II). We tested for an association between pre-treatment HRV and clinical outcomes on the BDI-II using a linear mixed effects model. Although average BDI-II score significantly changed over time, these changes were not significantly associated with pre-treatment HRV (p = 0.60). This finding remained when adjusting for age, sex, and HR, individually and collectively. The current study did not find a relationship between pre-treatment HRV and response to low frequency rTMS. Other approaches using cardiac biomarkers may have potential for response prediction.