Autonomic Nervous System Response to Intermittent Theta-Burst Transcranial Magnetic Stimulation in Those With Major Depressive Disorder​​​: A Randomized Sham-Controlled Comparison of Heart Rate Variability and Pupillary Light Reflex.

Abstract

Objectives: To examine the acute and longitudinal effects of repetitive transcranial magnetic stimulation (rTMS) on-autonomic nervous system measures (ANS)-heart rate variability (HRV) and pupillary light reflex (PLR)-in adults with major depressive disorder (MDD). This pilot study explored the feasibility of measurement and associations with clinical outcomes.

Methods: Thirteen adults undergoing rTMS for MDD participated in a single-blind, randomized, sham-controlled initial session, followed by 30 open-label treatments. HRV indices [root mean square of successive differences (RMSSD), high-frequency power in normalized units (HFnu)] were recorded at baseline, during stimulation, and biweekly; PLR indices were assessed pre- and post-treatment at rTMS session #1 and at endpoint. Depression severity was measured with the Hamilton Rating Scale for Depression (HRSD). Mixed-effects linear models evaluated changes over time; correlations examined associations between ANS measures and symptom improvement.

Results: HRSD scores improved significantly across treatment (P<0.01), with 4 remitters, 4 responders, and 5 nonresponders. No significant changes were observed in HRV or PLR for the entire sample over the treatment course. However, PLR maximum constriction velocity (MCV) decreased in the active condition versus sham at rTMS session #1 (P<0.05). There were no significant correlations between changes in HRSD scores and changes in either HRV or PLR variables.

Conclusions: Compared with sham stimulation, rTMS induced hyperacute parasympathetic effects on the ANS, as measured by PLR MCV, but this effect was short-lived. ANS measures showed no overall group change over the course of rTMS and no relationship to improvement in depression symptoms.