Vagus nerve stimulation: An update on a novel treatment for treatment-resistant depression

ABSTR A C T In this review, we provide an overview of essential clinical trials examining the effect of vagal nerve stimulation (VNS) in treatment-resistant depression (TRD), the applicable neuroanatomy of the vagus nerve, and the pro-posed mechanism of action (MOA) of VNS in TRD.Vagal nerve stimulation (VNS) is currently the only FDA-approved neurostimulation treatment for severe treatment-resistant depression (TRD). The implanted VNS device sends electrical impulses to the left cervical vagus nerve, resulting in stimulation of afferent vagal brainstem pathways known to be associated with mood regulation. Within the last decade, several clinical trials have attempted to further elucidate this effect specif-ically in TRD. Early clinical trials including the D01, D02, and D03 trials showed promising evidence of the antidepressant efficacy and durability of VNS as a treatment for TRD. Later trials comparing VNS and treatment-as-usual (TAU) resulted in similar findings regarding antidepressant efficacy and durability. VNS was addi-tionally found to be beneficial in improving quality of life and suicidality among unipolar TRD patients and depression among bipolar TRD patients. Ongoing and future studies such as the RECOVER trial continue to investigate the psychiatric benefits of VNS within the TRD population. Although the MOA of VNS in TRD is still not fully understood, recent brain imaging studies and animal studies have proven instrumental in addressing this knowledge gap.

Automated summary

This review provides an overview of clinical trials examining the effect of vagal nerve stimulation (VNS) in treatment-resistant depression (TRD) and the proposed mechanism of action (MOA) of VNS in TRD. VNS has been shown to be an effective treatment for TRD, improving quality of life and reducing suicidality. Ongoing research is investigating the psychiatric benefits of VNS in the TRD population, and brain imaging studies and animal research are playing a crucial role in understanding the MOA of VNS in TRD.