Addressing Adverse Events of Transcutaneous Auricular Vagus Nerve Stimulation: A Systematic Review with a Newly Developed Standardized Questionnaire (taVNS-AEQ)

Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulatory therapy gaining interest for its neural mechanisms and therapeutic effects. Although taVNS is considered safe, adverse event (AE) reporting remains inconsistent, lacking standardized procedures for assessment and documentation. This study aims to characterize AEs associated with taVNS in the literature and develop a standardized instrument for consistent reporting and analysis. A descriptive review of taVNS studies was conducted following the PRISMA guidelines to categorize reported AEs. Based on these findings, a semi-structured taVNS Adverse Events Questionnaire (taVNS-AEQ) was developed for a standardized assessment. Its feasibility and usability were evaluated in a randomized crossover study involving real and sham taVNS. The search identified 203 taVNS studies; 71 reported AEs. However, only 26 of these studies included semi-structured data with severity rating. A total of 539 symptoms reported as absolute counts, along with data from Likert-scale symptom assessments, were categorized for standardized analysis across 2339 participants. The taVNS-AEQ includes four participant items, seven personnel items, and recommendations for documenting stimulation parameters. In a real-sham crossover study, the most frequent AEs were tingling, fatigue, and changes in concentration. The questionnaire demonstrated good feasibility and was translated into four languages. Current evidence on taVNS-related AEs is limited by the heterogeneous nature of the reporting. The taVNS-AEQ offers a standardized approach to AE assessment, potentially enhancing the quality and comparability of future studies on taVNS.