Effectiveness and Safety of Vagus Nerve Stimulation in the Treatment of Treatment-Resistant Depression: A Systematic Review and Meta-Analysis

Objective: To systematically evaluate the effectiveness and safety of vagus nerve stimulation (VNS) in treating treatment-resistant depression (TRD), and provide evidence-based support for clinical application. Methods: Following PRISMA guidelines, randomized controlled trials (RCTs) and pre-post controlled cohort studies on VNS for TRD published from January 2005 to June 2019 were retrieved from MEDLINE/PubMed, EMBASE, Web of Science, Cochrane Library, CNKI, and Wanfang databases. Literature quality was assessed using the Cochrane Risk of Bias Tool. Meta-analysis was performed with RevMan 5.0 software, with effect sizes represented by standardized mean difference (SMD) or risk ratio (RR). Heterogeneity was tested using the I 2 statistic, and sensitivity analysis was conducted to explore sources of heterogeneity. Results: A total of 7 studies (4 RCTs, 3 pre-post studies) involving 1,236 TRD patients (682 in the VNS group and 554 in the treatment-as-usual [TAU] group) were included. Meta-analysis showed that 12-month VNS treatment significantly reduced Montgomery-Åsberg Depression Rating Scale (MADRS) scores compared to baseline (SMD = -0.42, 95%CI = -0.61 to -0.23, P < 0.001), and the remission rate (MADRS ≤ 10) was significantly higher than in the TAU group (RR = 1.85, 95%CI = 1.32 to 2.59, P < 0.001). In terms of safety, the most common adverse events (AEs) with VNS were voice alteration (52.3%), cough (24.1%), and neck pain (18.7%), with most AEs resolving over time (e.g., dysphagia decreased from 13% to 4%). Conclusion: VNS demonstrates certain effectiveness in TRD, with long-term (≥12 months) treatment significantly improving depressive symptoms. It also exhibits good safety, with most AEs being tolerable. Title Page Title Effectiveness and Safety of Vagus Nerve Stimulation in the Treatment of Treatment-Resistant Depression: A Systematic Review and Meta-Analysis Authors Lu jingchao Affiliation Department of Neurosurgery, Shenzhen-Shantou Sun Yat-sen Memorial Hospital, Sun Yat-sen University Address: Shenshan Central Hospital, Henger Road, Zhanqian City, Shanwei City, Guangdong Province Corresponding Author Han chunyang Department of Neurosurgery, Shenzhen-Shantou Sun Yat-sen Memorial Hospital, Sun Yat-sen University Email: [[email protected]] Tel: +8613428872617

Vagus nerve stimulation (VNS); Treatment-resistant depression (TRD); Meta-analysis; Safety; Montgomery-Åsberg Depression Rating Scale (MADRS) Disclosure This manuscript has not been published or submitted to any other journal for consideration. All authors have approved the final version of the manuscript and agree with its submission. Supplementary Material File (effectiveness and safety of vagus nerve stimulation1.docx) - Download - 353.86 KB Information & Authors Information Version history Copyright This work is licensed under a Non Exclusive No Reuse License.

Authors Metrics & Citations Metrics Article Usage 203views 108downloads Citations Download citation Lu jingchao. Effectiveness and Safety of Vagus Nerve Stimulation in the Treatment of Treatment-Resistant Depression: A Systematic Review and Meta-Analysis. Authorea. 30 June 2025. DOI: https://doi.org/10.22541/au.175127966.62314745/v1 DOI: https://doi.org/10.22541/au.175127966.62314745/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu.