Noninvasive Neurostimulator Shows Efficacy in Episodic Migraine

Patients with episodic migraine with or without aura were recruited from 10 Italian tertiary headache centers. A total of 285 patients were enrolled, and 248 randomized: 122 to the active arm and 126 to the sham arm. A total of 117 patients completed the double-blind period in the active arm, and 123 patients in the sham arm. “We had a few discontinuations in both arms, one of which was due to the device,” Dr. Tassorelli and colleagues noted. “Demographic and baseline characteristics show typical pictures of patients with episodic migraine,” Dr. Tassorelli said. Study subjects were mostly young, mostly female, and mostly experiencing migraine without aura. Subjects had a mean of five attacks of migraine per month, a mean of six days of headache per month, and a mean monthly intake of five acute migraine medications. One-third of the patients were on stable prophylactic medications. About 40% of the patients were having moderate pain when they treated their first attack. One-third of them were experiencing mild pain, while 23% were experiencing severe pain in the active group and 15% were having severe pain in the sham group.

Stimulation Reduced Pain

The primary end point of the study was pain freedom at 120 minutes for the first attack. The investigators found a significant difference between the two arms at 30 minutes that became more evident at 60 minutes. At 120 minutes, there was a difference, “but we lost the statistical significance,” Dr. Tassorelli reported. “However, a more refined, post hoc repeated-measure analysis showed that the group treated with the active stimulation had significantly more pain relief than the sham stimulation over the 120-minute period.”

One of the secondary outcome measures was headache response for the first attack, meaning a transition from severe or moderate pain to mild or no pain. “There was some difference at 30 minutes, although it was not significant. It was almost significant at 60 minutes, and it was definitely significant between groups in favor of the active nVNS at 120 minutes,” Dr. Tassorelli said.

The rate of participants who had a therapeutic response for 50% of attacks or more at 120 minutes speaks to the consistency of the response. Almost half of the patients responded to nVNS at 120 minutes for 50% or more of all treated attacks—47.6% achieved mild or no pain at 120 minutes in the treatment group versus 32.3% in the sham group; 32.4% achieved pain freedom at 120 minutes in the treatment group versus 18.2% in the sham group.

“We did not have many adverse events in this study,” Dr. Tassorelli said. Adverse effects of nVNS, mainly application site discomfort, were infrequent, mild, and transitory. No serious adverse events were recorded, and none of the patients in the active treatment group discontinued treatment due to adverse events.

In summary, nVNS “proved superior to sham for pain freedom at 30 minutes and at 60 minutes, but not at 120 minutes, which was our primary end point,” said Dr. Tassorelli and colleagues. “However, repeated-measures analysis validated the primary end point, indicating the superiority of active stimulation over sham through 120 minutes. This study provides class one evidence for the efficacy of nVNS in the acute treatment of episodic migraine.”

This study was sponsored by electroCore.

—Glenn S. Williams