Vagus nerve stimulation and depression

Physiological and molecular mechanisms of transcutaneous auricular vagus nerve stimulation in depression

Invasive vagus nerve stimulation (VNS) is an approved treatment of treatment-resistant depression (TRD) in Europe and in USA. Because of the associated possible surgical complications as well as side effects, invasive VNS is applied limitedly in the treatment of depression. Transcutaneous auricular VNS (tVNS), on the other hand, is a non-invasive alternative to traditional invasive VNS. tVNS is still considered an experimental treatment for depression. This is due to the limited high-quality evidence from randomized clinical studies, the not yet fully understood biological mechanisms of action, along with overall limited knowledge about the optimal stimulation parameters. 

To address these issues, the AddVNS (augmentative tVNS) study was initiated. The AddVNS is a monocentric, exploratory-prospective, randomized, doubleblind, sham-controlled interventional study that recruits adult and legally competent patients with current MDD or bipolar disorder with current depression who are treated in Max Planck Institute of Psychiatry (MPIP) (either inpatient or day clinic treatment). The patients participating in the AddVNS study receive either tVNS or sham tVNS for a period of 6 weeks. The primary objective of the study is to identify biological, psychological, socio-economic, and clinical biomarkers associated with treatment progression and response to treatment in patients with depression undergoing tVNS. To achieve this, an exploratory design with an assessment of many different parameters including psychophysiology, imaging, blood-based multi-omics, microbiome, psychometrics and neuropsychology are used.

The strength of the study lies in its study design, as AddVNS is a randomized controlled trial combining a meticulous documentation of tthe tVNS procedure with a wide assessment of many different parameters. This makes the AddVNS study one of the most extensive studies of tVNS in depression to date.