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

Abstract Background Difficult-to-treat-Depression (DTD) is a highly prevalent and burdening mental illness. Approximately 25% of patients are considered as treatment-refractory. Vagus nerve stimulation (VNS) has been suggested a promising add-on treatment for these individuals. Still, a large proportion of patients treated with VNS lack sufficient response. Further knowledge of the pathogenesis of depression and predictive biomarkers are needed to improve treatment options, including the choice for VNS. QTc length has been suggested as a predictive marker for VNS treatment response. We aim to validate these findings and to identify physiological and haematological markers that might predict response to VNS treatment. Methods We retrospectively analysed a subsample of the ongoing RESTORE-LIFE study. Prior to VNS treatment, baseline QTc length, and baseline serum blood samples were analysed and associated with the severity (Montgomery-Åsperg Depression Rating Scale (MADRS)) and the prospective course (six-, and 12-months follow-up) of depression after VNS initiation. We performed linear multiple regression analyses and correlation analysis with a stepwise forward approach. Results Data from 53 patients with DTD were included in this retrospective analysis. In a linear multiple regression analysis, taking age, sex and body-mass-index (BMI) into account, QTc length did not predict MADRS scores after six-, and 12-months VNS, respectively. An exploratory stepwise linear multiple regression with a forward approach using hematological and sociodemographic variables as predictors identified four factors as the most relevant for depressive symptom reduction after six months VNS. Lower absolute neutrophil count, lower BMI, younger age, and higher low- density lipoprotein concentrations at baseline predicted a depressive MADRS score reduction after six-months VNS. Only absolute neutrophil count predicted symptom reduction after 12-months VNS. Discussion We could not replicate previous findings suggesting the QTc as a predictive marker of VNS treatment response. However, our findings suggest a significant association between absolute neutrophil count, BMI, and serum low-density lipoprotein and reduction of depression severity in individuals treated with VNS adjunctive to treatment as usual. However, further prospective studies are needed to validate these findings and clarify the underlying mechanisms. Such studies will provide a basis for personalized interventions in individuals with DTD.