Participant-Centered Tolerability of Transcutaneous Auricular Vagus Nerve Stimulation: Insights from Two Crossover Studies

Background Transcutaneous auricular vagus nerve stimulation (taVNS) is a promising noninvasive technique for modulating parasympathetic activity, yet optimal stimulation parameters and comprehensive tolerability profiles remain undefined. Traditional assessments of taVNS tolerability have focused narrowly on safety and adverse events, overlooking participant comfort and subjective experience, which are critical factors for adherence and clinical translation. Methods We conducted two randomized crossover trials in healthy adults to evaluate the tolerability of taVNS across different stimulation parameters. Study 1 compared two monophasic duty cycles (30s on/30s off vs. 10s on/10s off), while Study 2 compared monophasic and biphasic waveforms. Tolerability was assessed using questionnaires and semi-structured interviews, with secondary outcomes including heart rate variability (HRV), pain sensitivity, and cortical excitability. Results Both studies demonstrated high tolerability across all taVNS conditions, with low median ratings for pain and irritation. The most common sensations were tingling, tickling, or pricking, reported by the majority of participants but rated as mild. Qualitative analysis revealed nuanced preferences related to comfort, perceived effectiveness, and ease of adjustment to stimulation. No significant differences in secondary physiological outcomes were observed between conditions, though trends suggested parameter-specific effects on HRV and pain sensitivity. Conclusions Our findings highlight that taVNS is well tolerated in healthy adults, regardless of duty cycle or waveform, when tolerability is defined to include comfort and participant experience. Incorporating these dimensions into tolerability assessments may enhance protocol optimization and support broader adoption of taVNS in clinical practice. Further research in clinical populations is warranted. Clinical Trial Registration: https://clinicaltrials.gov , identifiers (NCT06381102 and NCT06614933).