Safety and tolerability of Transcutaneous Vagus Nerve stimulation in humans; a systematic review

Brain Stimul. 2018 Nov-Dec;11(6):1225-1238. doi: 10.1016/j.brs.2018.08.010. Epub 2018 Aug 23.

Abstract

Background: Transcutaneous Vagus Nerve stimulation (tVNS) may be an alternative to surgically implanted VNS for epilepsy and other diseases. However, its safety and tolerability profile is unclear.

Objective: We performed a systematic review of treatment harms from tVNS in humans.

Methods: A systematic published and grey literature search was carried out to identify studies which deployed tVNS in human subjects. Study authors were contacted for safety/tolerability data if these were not available in the publication. Databases were searched from 1966 to May 2017. We noted study type, population, stimulation parameters, type and prevalence of side effects and/or serious adverse events (SAE). We also noted whether side effects/SAE were considered to be related to the tVNS and the proportion of participants dropping out of studies due to side effects.

Results: 51 studies were included comprising a total of 1322 human subjects receiving tVNS. The most common side effects were: local skin irritation from electrode placement (240 participants, 18.2%), headache (47, 3.6%) and nasopharyngitis (23, 1.7%). Whilst heterogeneity in overall side effect event rates between studies was not accounted for by the frequency (Hz) or pulse width (ms) of stimulation, a minority (35 participants (2.6%)) dropped out of studies due to side effects. Overall, 30 SAE occurred but only 3 were assessed by the relevant researchers to be possibly caused by tVNS.

Conclusion: tVNS is safe and well tolerated at the doses tested in research studies to date.

Keywords: Adverse events; Electroceuticals; Neuromodulation; Safety; Vagus nerve stimulation.

Publication types

  • Systematic Review

MeSH terms

  • Epilepsy / diagnosis
  • Epilepsy / therapy
  • Exanthema / diagnosis
  • Exanthema / etiology
  • Headache / diagnosis
  • Headache / etiology
  • Heart Rate / physiology
  • Humans
  • Migraine Disorders / diagnosis
  • Migraine Disorders / therapy
  • Transcutaneous Electric Nerve Stimulation / adverse effects
  • Transcutaneous Electric Nerve Stimulation / methods*
  • Vagus Nerve / physiology*
  • Vagus Nerve Stimulation / adverse effects
  • Vagus Nerve Stimulation / methods*