Noninvasive Vagal Nerve Stimulation for the Treatment of Postural Orthostatic Tachycardia Syndrome: A Comprehensive Review

Abstract

Postural orthostatic tachycardia syndrome (POTS) is a complex and heterogeneous autonomic disorder with limited effective treatment options. Noninvasive neuromodulation, particularly transcutaneous vagus nerve stimulation (tVNS), has recently emerged as a promising adjunctive therapy; however, substantial knowledge gaps remain. This article reviews the current evidence and highlights key limitations in the application of tVNS for POTS, including the lack of robust randomized controlled trials, small sample sizes, and inconsistent stimulation protocols across studies. The heterogeneity of POTS subtypes and the absence of validated biomarkers further complicate the interpretation of therapeutic outcomes. In addition, real-world applicability, long-term safety, and the mechanistic pathways underlying tVNS effects in POTS are insufficiently understood. Emerging areas such as the use of neuroimaging, physiological biomarkers, and cognitive assessments offer opportunities to deepen mechanistic insight and refine patient selection. Future studies should prioritize patient phenotyping, protocol standardization, and comprehensive outcome measures to improve clinical translation. Integrating tVNS into multimodal treatment strategies could enhance individualized care for POTS, but rigorous, high-quality research is needed to establish its long-term efficacy and safety. Addressing these challenges will be critical for determining the therapeutic role of tVNS in this disabling condition.

Keywords: autonomic dysfunction; postural orthostatic tachycardia syndrome; transcutaneous vagus nerve stimulation.