Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis

Abstract

Transcutaneous auricular vagus nerve stimulation (taVNS) has been investigated as a novel neuromodulation tool. Although taVNS is generally considered safe with only mild and transient adverse effects (AEs), those specifically caused by taVNS have not yet been investigated. This systematic review and meta-analysis on taVNS aimed to (1) systematically analyze study characteristics and AE assessment, (2) characterize and analyze possible AEs and their incidence, (3) search for predictable risk factors, (4) analyze the severity of AE, and (5) suggest an evidence-based taVNS adverse events questionnaire for safety monitoring. The articles searched were published through April 7, 2022, in Medline, Embase, Web of Science, Cochrane, and Lilacs databases. In general, we evaluated 177 studies that assessed 6322 subjects. From these, 55.37% of studies did not mention the presence or absence of any AEs; only 24.86% of the studies described that at least one adverse event occurred. In the 35 studies reporting the number of subjects with at least one adverse event, a meta-analytic approach to calculate the risk differences of developing an adverse event between active taVNS and controls was used. The meta-analytic overall adverse events incidence rate was calculated for the total number of adverse events reported on a 100,000 person-minutes-days scale. There were no differences in risk of developing an adverse event between active taVNS and controls. The incidence of AE, in general, was 12.84/100,000 person-minutes-days of stimulation, and the most frequently reported were ear pain, headache, and tingling. Almost half of the studies did not report the presence or absence of any AEs. We attribute this to the absence of AE in those studies. There was no causal relationship between taVNS and severe adverse events. This is the first systematic review and meta-analysis of transcutaneous auricular stimulation safety. Overall, taVNS is a safe and feasible option for clinical intervention.

Understanding the Neuroplastic Effects of Auricular Vagus Nerve Stimulation in Animal Models of Stroke: A Systematic Review and Meta-Analysis

“…Our recent meta-analysis of 167 studies assessing 5,827 subjects showed that this technique is a safe and feasible option for intervention, with a low incidence of adverse events and no severe adverse events reported associated with the stimulation. 12…”

“…[28][29][30][31][32] However, aVNS has been demonstrated to be a more feasible, accessible, and a safer therapy. 12…”

“…Our recent meta-analysis of 167 studies assessing 5,827 subjects showed that this technique is a safe and feasible option for intervention, with a low incidence of adverse events and no severe adverse events reported associated with the stimulation. 12 TaVNS can affect many of the bodily processes that the vagus nerve is engaged in, meaning it could be an intervention to a broad range of diseases, such as depression, diabetes, Alzheimer's disease, arthritis, and stroke. For instance, a recent systematic review performed by our group has demonstrated the taVNS electroencephalographic effects current stage of evidence and the lack of homogenous studies and standardized metrics in the field.…”

“…9 Furthermore, aVNS has been investigated in a variety of conditions, such as epilepsy, tinnitus, depression, Alzheimer's disease, Schizophrenia, pain, migraine, and Parkinson's disease, being considered safer, more accessible, and less invasive alternative than the surgical device. [9][10][11][12] Currently, animal studies seem to be having positive results regarding the reestablishment of motor function in rats with post stroke sequelae after aVNS. [13][14][15][16][17][18][19][20][21][22] However, there is a lack of full understanding and categorization of the current evidence, especially regarding the mechanisms behind aVNS's effects that can be further analyzed.…”

Editorial: Neuromodulation in COVID-19: From basic research to clinical applications

“…The brain chemistry, nociceptive processing, inflammation, and autonomic function are modulated by neurostimulation for different therapeutic purposes ( Li et al, 2015 ; Babygirija et al, 2017 ; Kaniusas et al, 2019a ). Even though neuromodulation therapy is generally considered safe with only mild and transient adverse effects ( Redgrave et al, 2018 ; Kim et al, 2022 ), the mechanistic understanding of neuromodulation is still incomplete ( Yap et al, 2020 ). While methodological standardization of the therapy is in progress ( Farmer et al, 2021 ), personalization of neuromodulation is still insufficient ( Yu et al, 2022 ; Kaniusas et al, 2019b ) for a successful translation of neuromodulation into mainstream clinical practice ( Goggins et al, 2022 ).…”