Repetitive Transcranial Magnetic Stimulation for Treatment-resistant Depression: Autonomic Correlates via Heart Rate Variability and Pupillometry
Mehek Sharma1, William V. McCall2, Peter B. Rosenquist2
1Medical College of Georgia, 2Psychiatry and Health Behavior, Medical College of Georgia
Objective:

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).

 

Background:

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.

Design/Methods:
Thirteen adults with MDD underwent randomized active and sham rTMS using Magventure-X-100 in the first session, followed by 30 daily active sessions (600 pulses/session at 120% motor threshold). Depression severity was assessed using the Hamilton Depression Rating Scale (HDRS) at baseline, weeks 2, 4, and 6. HRV was assessed via ECG for 5 minutes before, during, and after rTMS. Pupillometry was performed using the PLR-3000 with a 17-ms light flash at 10 µW. HRV and pupillometry collected at first randomization were compared between active and sham conditions.
Results:

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).

Conclusions:

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.

 

10.1212/WNL.0000000000213100
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