For patients with episodic migraines, preventive noninvasive vagus nerve stimulation treatment was similar to sham stimulation treatment in reducing days with migraines, according to a study published in Cephalalgia.

The aim of this randomized, double-blind, sham-controlled, phase 3 study, PREMIUM trial (NCT02378844), was to assess the efficacy and safety of noninvasive vagus nerve stimulation as a preventive treatment for patients with episodic migraines. The timeline of this study included a 4-week period without the study treatment, a 12-week double-blind, randomly assigned study period with patients receiving either the noninvasive vagus nerve stimulation or the sham stimulation, and then a 24-week open-label period. Patients were included in the study if they met the criteria for a diagnosis of migraine with or without aura, according to the International Classification of Headache Disorders, 3rd edition.

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The noninvasive vagus nerve stimulation treatment included a low-voltage electrical signal that generated a 24-V peak voltage and 60-mA peak output current. The sham treatment included a low-frequency biphasic direct current signal meant to be felt but not high enough to cause any stimulation. Both cohorts were administered 2 treatments 3 times a day as a preventive measure. Data were collected on an electronic migraine diary and included information on headaches, medications, adverse events, and stimulation treatments. Primary outcomes were the number of migraines, the need for acute medication to treat migraines, treatment satisfaction, and rate of adverse events.

Of the 332 patients included in the double-blind, randomly assigned study period, 165 were in the noninvasive vagus nerve stimulation treatment cohort and 167 were in the sham stimulation treatment cohort. Additionally, 269 patients entered the open-label study period, with 138 in the noninvasive vagus nerve stimulation treatment cohort and 131 in the sham stimulation treatment cohort. Baseline demographics were comparable between the cohorts.

Migraine days per month were reduced by 2.26 days in the noninvasive vagus nerve stimulation treatment cohort and by 1.80 days in the sham stimulation treatment cohort (P =.15). Headache days per month were reduced by 2.73 days in the noninvasive vagus nerve stimulation treatment cohort and by 2.11 days in the sham stimulation treatment cohort (P =.10). In the noninvasive vagus nerve stimulation treatment cohort, 31.9% experienced a ≥50% reduction in the number of migraine days and 25% in the sham stimulation treatment cohort experienced a ≥50% reduction in the number of migraine days (P =.19).

The noninvasive vagus nerve stimulation treatment had a larger therapeutic effect on patients with auras (P =.061) than on patients without auras (P =.15). Acute medication days per month were reduced by 1.9 days in the noninvasive vagus nerve stimulation treatment cohort and by 1.35 in the sham stimulation treatment cohort (P =.11).

Post hoc analysis indicated that patients who were ≥67% adherent to the noninvasive vagus nerve stimulation treatment protocol experienced significant therapeutic gains in the reduction of migraines and headaches and the need for acute medications compared with the sham stimulation treatment cohort.

Both cohorts, 95% in the noninvasive vagus nerve stimulation treatment cohort and 93% in the sham stimulation treatment cohort, reported that their treatment was somewhat or very easy to use. No serious adverse events were reported, and the most common events were rash, pain, erythema, discomfort at the application site, and dizziness.

Limitations of this study include the sham treatment inadvertently stimulating the vagus nerve, using bilateral stimulation, and the low treatment adherence to complete treatment 3 times a day as directed by the treatment protocol.

The researchers concluded that although noninvasive vagus nerve stimulation was not shown to be significantly superior to sham stimulation in this study, “[non-invasive vagus nerve stimulation] was further established as a well-tolerated and safe therapy for primary headache.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Diener HC, Goadsby PJ, Ashina M, et al. Non-invasive vagus nerve stimulation (nVNS) for the preventive treatment of episodic migraine: the multicentre, double-blind, randomised, sham-controlled PREMIUM trial [published online Sept. 15, 2019]. Cephalalgia. doi: 10.1177/0333102419876920