title: 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.
authors.affiliation: Headache Center, Carlo Besta Neurological Institute and Foundation, Via Celoria 11, 20133, Milan, Italy.
authors.forename: Licia
authors.initials: L
authors.lastname: Grazzi
authors.affiliation: Headache and Pain Unit, Istituto di Ricovero e Cura a Carattere Scientifico, San Raffaele Pisana, Via della Pisana 235, 00163, Rome, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Egeo
authors.affiliation: Carolina Headache Institute, 6114 Fayetteville Rd., Suite 109, 27713, Durham, NC, USA.
authors.forename: Anne H
authors.initials: AH
authors.lastname: Calhoun
authors.affiliation: North American Science Associates Inc., 4050 Olson Memorial Highway, Suite 450, 55422, Minneapolis, MN, USA.
authors.forename: Candace K
authors.initials: CK
authors.lastname: McClure
authors.affiliation: electroCore, LLC, 150 Allen Road, Suite 201, 07920, Basking Ridge, NJ, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Liebler
authors.affiliation: Headache and Pain Unit, Istituto di Ricovero e Cura a Carattere Scientifico, San Raffaele Pisana, Via della Pisana 235, 00163, Rome, Italy. piero.barbanti@sanraffaele.it.
authors.forename: Piero
authors.initials: P
authors.lastname: Barbanti
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D008598:Menstruation; D008881:Migraine Disorders / Q000188:drug therapy / Q000517:prevention & control*; D010147:Pain Measurement; D016896:Treatment Outcome; D014363:Tryptamines / Q000627:therapeutic use; D055536:Vagus Nerve Stimulation / Q000379:methods*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D014363:Tryptamines
keywords: Menstrual migraine; Menstrually related migraine; Prophylactic treatment; Vagus nerve