Chronic migraine headache prevention with noninvasive vagus nerve stimulation

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.ClinicalTrials.gov 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.

Targeting pericranial nerve branches to treat migraine: Current approaches and perspectives

“…This modest beneficial effect was confirmed in the subsequent open-label phase (45), but further studies are clearly needed to determine the role of tVNS in migraine management. Besides neck muscle contractions in some patients, there were no significant adverse effects.…”

“…The studies performed up to now with the noninvasive devices indicate that compliance may be the real challenge to solve in RCTs and in clinical practice (45).…”

Spotlight on cervical vagus nerve stimulation for the treatment of primary headache disorders: a review

“…A randomized double-blind, sham-controlled multicenter trial (EVENT) solely evaluated the preventive value and safety/tolerability in chronic migraine with a slightly different stimulation protocol compared to the previous migraine/nVNS studies 14. In total, 48 CM patients were enrolled and a meaningful frequency reduction was observed in the randomized phase (nVNS −1.4 days vs. 0.2 days), while the open-label phase nVNS (120 sec dose, right sided, at 5–10 min interval) was associated with significantly decreased headache days/month (nVNS −3.6 vs. −2.5 days, p <0.05).…”

Migraine Prevention Using Different Frequencies of Transcutaneous Occipital Nerve Stimulation: A Randomized Controlled Trial

“…The Food and Drug Administration recently approved the first medical TENS device for prevention of episodic migraines in adult patients; the device stimulates the supratrochlear and supraorbital nerves 1,19,[28][29][30] The vagus nerve has also been evaluated in this context. 31 Although several devices delivering transcutaneous occipital nerve stimulation (tONS) 17 are available, no high-quality trial has yet been conducted, and the ability of tONS to prevent migraine has not been well-investigated. Based on previous work, we conducted a pilot trial in which migraine patients underwent 1 month of treatment.…”