Predictors of treatment response to adjunctive vagus nerve stimulation in difficult-to-treat depression: a retrospective data analysis

BackgroundVagus nerve stimulation (VNS) is an FDA-approved invasive neuromodulatory treatment for Difficult-to-treat-Depression (DTD). However, approximately 50% of patients do not respond sufficiently to VNS. A previous study found that the baseline corrected QT (QTc) interval correlates with later VNS treatment response. We aimed to replicate this finding and further explored physiological and blood-based predictors of VNS response. MethodsData of 53 patients treated with VNS were pooled between three VNS centres. All available QTc data and blood-based parameters were used. We conducted a regression analysis with baseline QTc length and Montgomery-[A]sperg Depression Rating Scale (MADRS) changes after six- and 12- months of VNS. For analysis of blood-based variables, we used exploratory correlation analysis with a stepwise forward regression approach. ResultsAfter correction for sex, age and body mass index (BMI) and medication, baseline QTc intervals did not correlate with MADRS change at either follow-up. Exploratory regression analysis identified four factors associated with MADRS reduction after six-months of VNS: lower absolute neutrophil count (ANC), BMI, younger age, and higher low-density lipoprotein (LDL) levels. Only absolute neutrophil count correlated with MADRS change after 12-months VNS. DiscussionWith a larger sample and relevant covariates, we did not replicate a previous finding that baseline QTc interval correlates with later MADRS change upon antidepressant VNS. However, in exploratory analyses, blood-based markers indicated links between MADRS change and ANC, BMI, age, and serum LDL. These findings need to be verified in prospective, controlled studies to facilitate optimal prescription of antidepressant VNS.