Highlights
- •We compared active transcutaneous vagus nerve stimulation (tVNS) with a sham stimulation paradigm for treatment of drug-resistant epilepsy in a double-blind, randomized clinical trial.
- •Superiority of active tVNS vs. control tVNS could not be proven, but seizure frequency was significantly reduced in patients who completed the full active tVNS treatment period of 20 weeks.
- •Treatment adherence was high.
- •tVNS is a well tolerated treatment procedure.
Abstract
Background
Various brain stimulation techniques are in use to treat epilepsy. These methods usually
require surgical implantation procedures. Transcutaneous vagus nerve stimulation (tVNS)
is a non-invasive technique to stimulate the left auricular branch of the vagus nerve
at the ear conch.
Objective
We performed a randomized, double-blind controlled trial (cMPsE02) to assess efficacy
and safety of tVNS vs. control stimulation in patients with drug-resistant epilepsy.
Methods
Primary objective was to demonstrate superiority of add-on therapy with tVNS (stimulation
frequency 25 Hz, n = 39) versus active control (1 Hz, n = 37) in reducing seizure
frequency over 20 weeks. Secondary objectives comprised reduction in seizure frequency
from baseline to end of treatment, subgroup analyses and safety evaluation.
Results
Treatment adherence was 84% in the 1 Hz group and 88% in the 25 Hz group, respectively.
Stimulation intensity significantly differed between the 1 Hz group (1.02 ± 0.83 mA)
and the 25 Hz group (0.50 ± 0.47 mA; p = 0.006). Mean seizure reduction per 28 days
at end of treatment was –2.9% in the 1 Hz group and 23.4% in the 25 Hz group (p = 0.146).
In contrast to controls, we found a significant reduction in seizure frequency in
patients of the 25 Hz group who completed the full treatment period (20 weeks; n = 26,
34.2%, p = 0.034). Responder rates (25%, 50%) were similar in both groups. Subgroup
analyses for seizure type and baseline seizure frequency revealed no significant differences.
Adverse events were usually mild or moderate and comprised headache, ear pain, application
site erythema, vertigo, fatigue, and nausea. Four serious adverse events were reported
including one sudden unexplained death in epilepsy patients (SUDEP) in the 1 Hz group
which was assessed as not treatment-related.
Conclusions
tVNS had a high treatment adherence and was well tolerated. Superiority of 25 Hz tVNS
over 1 Hz tVNS could not be proven in this relatively small study, which might be
attributed to the higher stimulation intensity in the control group. Efficacy data
revealed results that justify further trials with larger patient numbers and longer
observation periods.
Keywords
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Article info
Publication history
Published online: January 20, 2016
Accepted:
November 14,
2015
Received in revised form:
November 10,
2015
Received:
August 21,
2015
Identification
Copyright
© 2015 Elsevier Inc. All rights reserved.
