The Mechanism of Action of Vagus Nerve Stimulation in Treatment-Resistant Depression

Stimulation of the left cervical vagus nerve, or vagus nerve stimulation (VNS), brings about an antidepressant response in a subset of patients with treatment-resistant depression (TRD). How this occurs is poorly understood; however, knowledge of the neuroanatomic vagal pathways, in conjunction with functional brain imaging studies, suggests several brain regions associated with mood regulation are critical: brainstem nuclei (locus coeruleus, dorsal raphe, and ventral tegmental area), thalamus, and insular and prefrontal cortex. Furthermore, animal studies suggest that VNS enhances neuroplasticity and changes in neuronal firing patterns. Continued study to better understand the mechanism of action of VNS in TRD is warranted.