Non-invasive Vagus Nerve Stimulation (nVNS) as mini-prophylaxis for menstrual/menstrually related migraine: an open-label study

Abstract

Background: Menstrual migraine and menstrually related migraine attacks are typically longer, more disabling, and less responsive to medications than non-menstrual attacks. The aim of this study was to evaluate the efficacy, safety, and tolerability of non-invasive vagus nerve stimulation for the prophylactic treatment of menstrual migraine/menstrually related migraine.

Methods: Fifty-six enrolled subjects (menstrual migraine, 9 %; menstrually related migraine, 91 %), 33 (59 %) of whom were receiving other prophylactic therapies, entered a 12-week baseline period. Fifty-one subjects subsequently entered a 12-week treatment period to receive open-label prophylactic non-invasive vagus nerve stimulation adjunctively (31/51; 61 %) or as monotherapy (20/51; 39 %) on day -3 before estimated onset of menses through day +3 after the end of menses.

Results: The number of menstrual migraine/menstrually related migraine days per month was significantly reduced from baseline (mean ± standard error, 7.2 ± 0.7 days) to the end of treatment (mean ± standard error, 4.7 ± 0.5 days; P < 0.001) (primary end point). Of all subjects, 39 % (95 % confidence interval: 26 %, 54 %) (20/51) had a ≥ 50 % reduction (secondary end point). For the other secondary end points, clinically meaningful reductions in analgesic use (mean change ± standard error, -3.3 ± 0.6 times per month; P < 0.001), 6-item Headache Impact Test score (mean change ± standard error, -3.1 ± 0.7; P < 0.001), and Migraine Disability Assessment score (mean change ± standard error, -11.9 ± 3.4; P < 0.001) were observed, along with a modest reduction in pain intensity (mean change ± standard error, -0.5 ± 0.2; P = 0.002). There were no safety/tolerability concerns.

Conclusions: These findings suggest that non-invasive vagus nerve stimulation is an effective treatment that reduces the number of menstrual migraine/menstrually related migraine days and analgesic use without safety/tolerability concerns in subjects with menstrual migraine/menstrually related migraine. Randomised controlled studies are warranted.

Keywords: Menstrual migraine; Menstrually related migraine; Prophylactic treatment; Vagus nerve.

Fig. 1

Non-invasive Vagus Nerve Stimulation Device. Image provided courtesy of electroCore, LLC

Fig. 2

Change in Number of MM/MRM Days per Month (ITT Population)^a. Abbreviations: ITT, intention-to-treat; nVNS, non-invasive vagus nerve stimulation; SEM, standard error of the mean. ^aData are mean ± SEM; mean differences between treatment groups may not reflect calculated differences because of rounding; P values are from the t test; missing data were imputed using the last observation carried forward

Fig. 3

Change in Analgesic Use per Month (ITT Population)^a. Abbreviations: ITT, intention-to-treat; nVNS, non-invasive vagus nerve stimulation; SEM, standard error of the mean. ^aData are mean ± SEM; mean differences between treatment groups may not reflect calculated differences because of rounding; P values are from the t test; missing data were imputed using the last observation carried forward

Fig. 4

Change in HIT-6™ Migraine Disability (ITT Population)^a. Abbreviations: HIT-6, 6-item Headache Impact Test; ITT, intention-to-treat; nVNS, non-invasive vagus nerve stimulation; SEM, standard error of the mean. ^aData are mean ± SEM; mean differences between treatment groups may not reflect calculated differences because of rounding; P values are from the t test; missing data were imputed using the last observation carried forward. ^bOne subject had missing HIT-6 data for both the baseline and nVNS periods

Fig. 5

Change in MIDAS Migraine Disability (ITT Population)^a. Abbreviations: ITT, intention-to-treat; MIDAS, Migraine Disability Assessment; nVNS, non-invasive vagus nerve stimulation; SEM, standard error of the mean. MIDAS score (a) and MIDAS grade (b). ^aData are mean ± SEM; mean differences between treatment groups may not reflect calculated differences because of rounding; P values were from the t test; missing data were imputed using the last observation carried forward. ^bOne subject had missing MIDAS grade data for both the baseline and nVNS periods

Fig. 6

Change in Pain Intensity (ITT Population)^a. Abbreviations: ITT, intention-to-treat; nVNS, non-invasive vagus nerve stimulation; SEM, standard error of the mean. ^aData are mean ± SEM; mean differences between treatment groups may not reflect calculated differences because of rounding; P values are from the t test; missing data were imputed using the last observation carried forward