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

BACKGROUND: 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.

METHODS: 30 patients suffering from alcohol use disorder, undergoing AWS, stable on medication, were recruited in this open-label, single-arm pilot trial with repeated measure design. Peripheral VNS (monophasic volt impulses of 1ms, alternating polarity, frequency 1 Hz, amplitude 4mV) was administered at the left cymba conchae for 72 hours, followed by pupillometry under a tropicamide challenge. We assessed craving with a visual analog scale. We used pupillary mean as dependent variable in a repeated measures ANOVA (rmANOVA).

RESULTS: A repeated measures ANOVA resulted in a significant difference for pupillary diameter across time and condition (F2,116 = 27.97, p < .001, ηp 2 > .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).

CONCLUSION: 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.