Chronic migraine headache prevention with noninvasive vagus nerve stimulation: The EVENT study

Abstract

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.

© 2016 American Academy of Neurology.

Figures

Figure 1. Participant disposition

nVNS = noninvasive vagus nerve stimulation.

Figure 2. Effects of noninvasive vagus nerve stimulation (nVNS) on the change in number of headache days per 28 days

(A) Mean change in headache days per 28 days from baseline through the open-label phase (intent-to-treat population). Imputation for missing data was performed using the last observation carried forward. aReceived open-label nVNS after month 2. *p < 0.05 vs baseline. (B) Mean change in headache days per 28 days from baseline through the duration of nVNS treatment (per-protocol completer population). aThe 2-, 4-, and 6-month completers were from the 59 participants initially randomized to either nVNS or sham treatment. bThe 8-month completers were from the 30 participants initially randomized to nVNS treatment. cOne participant who completed 8 months of nVNS initiated gabapentin treatment during the study and was therefore excluded from 8-month completer analyses. *p < 0.05 vs baseline. **p < 0.01 vs baseline.

Figure 3. Participants who achieved a ≥50% treatment response with noninvasive vagus nerve stimulation (nVNS) (per-protocol completer population)

aThe 2-, 4-, and 6-month completers were from the 59 participants initially randomized to either nVNS or sham treatment. bThe 8-month completers were from the 30 participants initially randomized to nVNS treatment. cOne participant who completed 8 months of nVNS initiated gabapentin treatment during the study and was therefore excluded from 8-month completer analyses.