Pretreatment pupillary reactivity is associated with differential early response to 10 Hz and intermittent theta-burst repetitive transcranial magnetic stimulation (rTMS) treatment of major depressive disorder (MDD)

Background: Repetitive Transcranial Magnetic Stimulation (rTMS) is an effective treatment for Major Depressive Disorder (MDD). Two common rTMS protocols, 10 Hz and intermittent theta burst stimulation (iTBS), have comparable rates of efficacy in groups of patients. Recent evidence suggests that some individuals may be more likely to benefit from one form of stimulation than the other. The pretreatment pupillary light reflex (PLR) is significantly associated with response to a full course of rTMS using heterogeneous stimulation protocols. Objective: To test whether the relationship between pretreatment PLR and early symptom improvement differed between subjects treated with iTBS or 10 Hz stimulation. Methods: PLR was measured in 52 subjects who received solely 10 Hz (n = 35) or iTBS (n = 17) to left dorsolateral prefrontal cortex (DLPFC) for the first ten sessions of their treatment course. Primary outcome measure was the percent change of Inventory of Depressive Symptomatology - Self Report (IDS-SR) from session 1 to session 10. Results: There was a positive association between normalized maximum constriction velocity (nMCV) and early improvement in subjects receiving 10 Hz stimulation (R = 0.48, p = 0.004) and a negative association in subjects receiving iTBS (R =-0.52, p = 0.03). ANOVA revealed a significant interaction between nMCV and the type of initial stimulation (p = 0.001). Among subjects with low nMCV, those initially treated with iTBS showed 2.6 times greater improvement after 10 sessions (p = 0.01) than subjects initially receiving 10 Hz stimulation. Conclusion: nMCV may detect physiologic differences between those likely to benefit from 10 Hz or iTBS treatment. Future studies should examine whether PLR could guide prospective treatment selection.