Evaluate the effect of repetitive transcranial magnetic stimulation (rTMS) on depressive symptoms and autonomic function, measured by heart rate variability (HRV) and pupillary light reflex (PLR), in treatment-resistant major depressive disorder (MDD).

Treatment-resistant depression presents significant clinical challenges and is associated with dysregulation of brain networks involved in mood and autonomic control. rTMS is thought to influence these neural circuits, potentially restoring balance in both emotional and autonomic regulation. HRV and PLR reflect autonomic function, with higher HRV suggesting better emotional resilience, and may serve as biomarkers of treatment response; however, their clinical relevance remains underexplored.

Repeated measures analysis revealed no significant changes in HRV measures - including Root Mean Square of Successive Differences (RMSSD) and high-frequency normalized units (HF [nu]) - across the full course of treatment despite a statistically significant reduction in depressive symptoms, as measured by the HRDS (p < 0.05). Pupillometry revealed short-term autonomic effects, with maximum constriction velocity (MCV) decreasing significantly in the active rTMS group compared to sham (p = 0.05).

Together these results suggest that while active rTMS stimulation may influence ANS indicators in the treatment room, these measures are relatively stable over time within individuals and show limited fluctuation in response to changes in clinical status.