REVIEW article
Front. Psychiatry
Sec. Neurostimulation
This article is part of the Research TopicUnderlying Neural Mechanisms of Non-invasion Brain Stimulation in the Treatment of Psychiatric Disorders: Evidence from Neuroimaging Studies Volume IIView all 8 articles
Transcutaneous Auricular Vagus Nerve Stimulation for Major Depressive Disorder: Current Evidence and Future Research Directions
Provisionally accepted
Jifei Sun1,2*
Jing Zhang3Hongwei Liu2Yuan Zhou2Chenjie Ma2Xiaojian Zhang2Shuqing Liu2Jingxue Zhao1Chunbo Hao2*Xue Xiao4- 1Guang’anmen Hospital, China Academy of Chinese Medical Science, Beijing, Cocos Islands
- 2Shunyi Hospital of Beijing Traditional Chinese Medicine Hospital, Beijing, China
- 3Beijing Fengtai You'anmen Hospital, Beijing, China
- 4Beijing Tsinghua Changgung Hospital, Beijing, China
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[Abstract]: Major depressive disorder (MDD) causes a significant global disease burden, yet existing pharmacological treatments are often limited by side effects and poor adherence. Transcutaneous auricular vagus nerve stimulation (taVNS), a promising non-invasive neuromodulation technique, offers a safe and accessible therapeutic alternative. This narrative review synthesizes current clinical evidence, explores potential mechanisms of action, and outlines future research directions for taVNS in MDD. Clinical studies consistently indicate that taVNS significantly alleviates depressive symptoms. Its therapeutic effects are mediated through multiple pathways, including anti-inflammatory regulation, autonomic modulation, neurotransmitter restoration, functional brain network reorganization, and the gut-brain axis. Despite these promising findings, clinical translation is hindered by methodological heterogeneity, small sample sizes, and a lack of long-term follow-up data. To advance clinical application, future research should prioritize establishing standardized stimulation protocols to reduce methodological heterogeneity, integrating multi-omics approaches to systematically decipher the "neuro-immune-endocrine-gut-brain" regulatory axis, and leveraging machine learning algorithms to identify multimodal predictive biomarkers for precision medicine. By integrating these advanced approaches, taVNS has the potential to become a robust, first-line therapeutic option for depression.
Keywords: gut-brain axis, Major Depressive Disorder, Narrative review, Neuroimaging, Neuromodulation, Transcutaneous auricular vagus nerve stimulation
Received: 16 Jan 2026; Accepted: 16 Feb 2026.
Copyright: © 2026 Sun, Zhang, Liu, Zhou, Ma, Zhang, Liu, Zhao, Hao and Xiao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jifei Sun
Chunbo Hao
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