eTNS Treatment Shows Varying Efficacy in Migraine With Aura vs Without Aura

Compared with patients with migraine without aura, those with migraine with aura demonstrate lower rescue medication use and greater sustained pain relief following external trigeminal nerve stimulation (eTNS) treatment, according to study results presented at the 2025 American Headache Society (AHS) Annual Scientific Meeting, held from June 19-22, in Minneapolis, Minnesota, and virtually.

Researchers conducted a post hoc subgroup analysis using data from TEAM (ClinicalTrials.gov Identifier: NCT03465904), a randomized, double-blind, sham-controlled phase 3 trial evaluating the efficacy of eTNS for acute migraine treatment. A total of 538 participants were randomly assigned to receive either verum (n=259) or sham (n=279) eTNS. Participants were stratified by migraine subtype: 224 with migraine with aura and 314 with migraine without aura.

The researchers used logistic regression and chi-square analyses to compare outcomes between subgroups, with additional interaction terms included to assess heterogeneity of treatment effect (HTE).

At baseline, compared with participants with migraine without aura, those with migraine with aura were more likely to report severe headache pain (50.0% vs 32.8%; P <.001) and were more often men (23.2% vs 13.7%; P =.004).

Moderate headache pain was more commonly reported in the migraine without aura group (67.2% vs 49.1%; P <.001).

Compared with sham, among those in the migraine without aura subgroup receiving verum eTNS, they had significantly higher rates of resolution of the most bothersome symptom at 2 hours (55.5% vs 39.3%; P =.004), pain relief at 2 hours (69.9% vs 50.0%; P <.001), and sustained pain relief at 24 hours (42.5% vs 28.0%; P =.007).

Across the total sample and within both treatment arms, compared with participants with migraine without aura, those with migraine with aura used rescue medications less frequently.

Rescue medication use was 19.6% vs 45.5% overall (P <.001), 24.2% vs 39.7% within the verum group (P =.002), and 18.0% vs 50.6% in the sham group (P <.001).

Compared with individuals with migraine without aura, those with migraine with aura also reported higher rates of pain relief at 2 hours (63.1% vs 50.0%; P =.032) and sustained pain relief at 24 hours (44.1% vs 28.0%; P =.005).

Although no statistically significant subgroup-by-treatment interactions were identified, a clinically meaningful HTE was observed in rescue medication use between 2- and 24-hours post-treatment, with an absolute effect of –10.9% in the migraine without aura group and 3.2% in the migraine with aura group.

“Further studies are needed to explore the potential interactions of trigeminal nerve stimulation and neurophysiological mechanisms of MA [migraine with aura] and CSD [cortical spreading depression] which may have substantial impact beyond headache medicine,” the researchers concluded.