Transcutaneous cervical vagus nerve stimulation reduces behavioral and physiological manifestations of withdrawal in patients with opioid use disorder: A double-blind, randomized, sham-controlled pilot study

Author: Asim H Gazi1, Anna B Harrison2, Tamara P Lambert3, Malik Obideen4, Parvaneh Alavi4, Nancy Murrah5, Lucy Shallenberger5, Emily G Driggers5, Rebeca Alvarado Ortega4, Brianna P Washington4, Kevin M Walton6, Justine W Welsh4, Viola Vaccarino7, Amit J Shah8, Yi-Lang Tang9, Rahul Gupta9, Sudie E Back10, Omer T Inan11, J Douglas Bremner12
Affiliation:
1 School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA, USA. Electronic address: asim.gazi@gatech.edu.
2 School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
3 Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
4 Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, USA.
5 Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
6 Clinical Research Grants Branch, Division of Therapeutics and Medical Consequences, National Institute on Drug Abuse, Bethesda, MD, USA.
7 Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA; Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA.
8 Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA; Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA; Atlanta Veterans Affairs Health Care System, 1670 Clairmont Road, Decatur, GA, USA.
9 Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, USA; Atlanta Veterans Affairs Health Care System, 1670 Clairmont Road, Decatur, GA, USA.
10 Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA.
11 School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA, USA; Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
12 Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, USA; Atlanta Veterans Affairs Health Care System, 1670 Clairmont Road, Decatur, GA, USA; Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, USA. Electronic address: jdbremn@emory.edu.
Conference/Journal: Brain Stimul
Date published: 2022 Aug 27
Other: Special Notes: doi: 10.1016/j.brs.2022.08.017. , Word Count: 251


Background:
Opioid Use Disorder (OUD) is a serious public health problem, and the behavioral and physiological effects of opioid withdrawal can be a major impediment to recovery. Medication for OUD is currently the mainstay of treatment; however, it has limitations and alternative approaches are needed.

Objective:
The purpose of this study was to assess the effects of transcutaneous cervical vagus nerve stimulation (tcVNS) on behavioral and physiological manifestations of acute opioid withdrawal.

Methods:
Patients with OUD undergoing acute opioid withdrawal were randomly assigned to receive double blind active tcVNS (N = 10) or sham stimulation (N = 11) while watching neutral and opioid cue videos. Subjective opioid withdrawal, opioid craving, and anxiety were measured using a Visual Analogue Scale (VAS). Distress was measured using the Subjective Units of Distress Scale (SUDS), and pain was measured using the Numerical Rating Scale (NRS) for pain. Electrocardiogram signals were measured to compute heart rate. The primary outcomes of this initial phase of the clinical trial (ClinicalTrials.gov NCT04556552) were heart rate and craving.

Results:
tcVNS compared to sham resulted in statistically significant reductions in subjective opioid withdrawal (p = .047), pain (p = .045), and distress (p = .004). In addition, tcVNS was associated with lower heart rate compared to sham (p = .026). Craving did not significantly differ between groups (p = .11).

Conclusions:
tcVNS reduces behavioral and physiological manifestations of opioid withdrawal, and should be evaluated in future studies as a possible non-pharmacologic, easily implemented approach for adjunctive OUD treatment.

Keywords: 6): opioid use disorder; And double-blind; Non-invasive; Sham-controlled; Vagus nerve stimulation; Withdrawal.

PMID: 36041704 DOI: 10.1016/j.brs.2022.08.017

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