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Chronic migraine headache prevention with noninvasive vagus nerve stimulation: The EVENT study
Stephen D Silberstein1, Anne H Calhoun2, Richard B Lipton2
1From Jefferson Headache Center (S.D.S.), Philadelphia, PA; Carolina Headache Institute (A.H.C.), Chapel Hill, NC; Montefiore Headache Center and Albert Einstein College of Medicine (R.B.L.), Bronx, NY; Hartford HealthCare Headache Center (B.M.G.), West Hartford, CT; Clinvest Headache Care Center (R.K.C.), Springfield, MO; MedLogix Communications, LLC (S.D.), Schaumburg, IL; electroCore, LLC (K.A.S., E.J.L.), Basking Ridge, NJ; NAMSA (C.M.), Minneapolis, MN; University of California San Francisco (P.J.G.); King's College London (P.J.G.), UK; and Michigan Headache and Neurological Institute (J.R.S.), Ann Arbor. B.M.G. was affiliated with Montefiore Headache Center, Bronx, NY, at the time of study completion. stephen.silberstein@jefferson.edu.
Objective:
To evaluate the feasibility, safety, and tolerability of noninvasive vagus nerve stimulation (nVNS) for the prevention of chronic migraine (CM) attacks.
Methods:
In this first prospective, multicenter, double-blind, sham-controlled pilot study of nVNS in CM prophylaxis, adults with CM (≥15 headache d/mo) entered the baseline phase (1 month) and were subsequently randomized to nVNS or sham treatment (2 months) before receiving open-label nVNS treatment (6 months). The primary endpoints were safety and tolerability. Efficacy endpoints in the intent-to-treat population included change in the number of headache days per 28 days and acute medication use.
Results:
Fifty-nine participants (mean age, 39.2 years; mean headache frequency, 21.5 d/mo) were enrolled. During the randomized phase, tolerability was similar for nVNS (n = 30) and sham treatment (n = 29). Most adverse events were mild/moderate and transient. Mean changes in the number of headache days were -1.4 (nVNS) and -0.2 (sham) (Δ = 1.2; p = 0.56). Twenty-seven participants completed the open-label phase. For the 15 completers initially assigned to nVNS, the mean change from baseline in headache days after 8 months of treatment was -7.9 (95% confidence interval -11.9 to -3.8; p < 0.01).
Conclusions:
Therapy with nVNS was well-tolerated with no safety issues. Persistent prophylactic use may reduce the number of headache days in CM; larger sham-controlled studies are needed.
Clinicaltrialsgov Identifier:
NCT01667250.
Classification Of Evidence:
This study provides Class II evidence that for patients with CM, nVNS is safe, is well-tolerated, and did not significantly change the number of headache days. This pilot study lacked the precision to exclude important safety issues or benefits of nVNS.
