Pupillary response to percutaneous auricular vagus nerve stimulation in alcohol withdrawal syndrome: A pilot trial

• Published in: Alcohol (Fayetteville, N.Y.) Vol. 114; pp. 61 - 68
• Main Authors: Treiber, M.C., Grünberger, J., Vyssoki, B., Szeles, J.C., Kaniusas, E., Kampusch, S., Stöhr, H., Walter, H., Lesch, O.M., König, D., Kraus, C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-02-2024; Elsevier Limited
• Subjects: Alcohol use; Alcohol withdrawal; Alcoholism - therapy; Autonomic Nervous System; Biomarkers; Chronic illnesses; Convulsions & seizures; Humans; neuromodulation psychophysiology pupillometry; Parasympathetic nervous system; Pilot Projects; Substance Withdrawal Syndrome - drug therapy; Vagus nerve; Vagus Nerve Stimulation; Austria; neuromodulation psychophysiology pupillometry; vagus nerve stimulation; autonomic nervous system; alcohol withdrawal
• ISSN: 0741-8329; 1873-6823; 1873-6823
• DOI: 10.1016/j.alcohol.2023.08.009

Autonomic symptoms in alcohol withdrawal syndrome (AWS) are associated with a sympathetic-driven imbalance of the autonomic nervous system. To restore autonomic balance in AWS, novel neuromodulatory approaches could be beneficial. We conducted a pilot trial with percutaneous auricular vagus nerve stimulation (pVNS) in AWS and hypothesized that pVNS will enhance the parasympathetic tone represented by a reduction of pupillary dilation in a parasympatholytic pharmacological challenge.
Thirty patients suffering from alcohol use disorder, undergoing AWS, and stable on medication, were recruited in this open-label, single-arm pilot trial with repeated-measure design. Peripheral VNS (monophasic volt impulses of 1 msec, alternating polarity, frequency 1 Hz, amplitude 4 mV) was administered at the left cymba conchae for 72 h, followed by pupillometry under a tropicamide challenge. We assessed craving with a visual analog scale. We used pupillary mean as the dependent variable in a repeated-measures ANOVA (rmANOVA).
A repeated-measures ANOVA resulted in a significant difference for pupillary diameter across time and condition (F(2,116) = 27.97, p < .001, ηp2 > .14). Tukey-adjusted post hoc analysis revealed a significant reduction of pupillary diameter after pVNS. Alcohol craving was significantly reduced after pVNS (p < .05, Cohen's d = 1.27).
Our study suggests that pVNS activates the parasympathetic nervous system in patients with acute AWS, and that this activation is measurable by pupillometry. To this end, pVNS could be beneficial as a supportive therapy for AWS. Potential confounding effects of anti-craving treatment should be kept in mind.
•pVNS inhibits pupil dilation in an anticholinergic challenge in alcohol withdrawal syndrome.•Novel neuromodulatory techniques may have the potential to mitigate symptoms of alcohol withdrawal syndrome.•pVNS decreased alcohol craving, though this effect could be confounded by treatment.