Noninvasive Vagus Nerve Stimulation Reduces Withdrawal-Related Affective Distress and Improves Functional Outcomes in Alcohol Use Disorder: A Feasibility and Acceptability Pilot Study.

Alcohol use disorder (AUD) is characterized by autonomic dysregulation and overactive brain stress systems, which manifests as pronounced negative emotional states in the absence of alcohol and can lead to functional impairment. The vagus nerve presents a promising novel treatment target for these symptoms. The aim of this pilot study was to evaluate the feasibility and acceptability of cervical noninvasive vagal nerve stimulation (nVNS) as a new treatment for AUD, and to assess whether nVNS can alleviate withdrawal-related affective distress and improve functional outcomes. In this double-blind, randomized controlled trial, male Veterans with AUD were randomly assigned to receive active (n = 9) or sham (n = 10) nVNS at baseline, self-administered stimulation for seven days, and returned for a follow-up visit. Treatment adherence and acceptability ratings were assessed. Behavioral self-report measures of affective distress (Patient Health Questionnaire [PHQ-8], State-Trait Anxiety Inventory-State, Beck Anxiety Inventory) and functional limitations (Drinker Inventory of Consequences [DrInC-2R], Brief Inventory of Psychosocial Functioning [BIPF]) were collected at baseline and follow-up. Linear mixed effects (LME) models were used to assess the impact of treatment group on outcome measures. Treatment adherence was high in both groups and did not statistically differ (94% nVNS group, 80% sham group; p = 0.14). Both groups assigned treatment acceptability ratings in the acceptable to highly acceptable range. LME results show significant group-by-time interactions for the PHQ-8 [p = 0.04], DrInC-2R [p = 0.02], and BIPF [p = 0.01]), indicating greater reductions in depressive symptoms, adverse alcohol-related consequences, and functional limitations after nVNS than with sham treatment. No statistically significant group-by-time interactions were observed for anxiety symptoms. To our knowledge, this is the first study to explore cervical nVNS as a potential new treatment for AUD-related symptoms. Findings provide support for feasibility of treatment delivery and patient acceptance, and initial evidence that nVNS can achieve significant reductions in depressive symptoms in addition to adverse alcohol-related consequences and psychosocial functional limitations in AUD.