Efficacy and safety of transcutaneous supraorbital nerve stimulation versus topiramate for migraine prevention: a non-inferiority randomized trial

Migraine remains a predominant neurological disorder that requires effective preventive therapies. Although topiramate is a well - recognized first - line pharmacotherapeutic approach, its use is often restricted by adverse reactions. Transcutaneous supraorbital nerve stimulation (tSNS) has emerged as a non - pharmacological alternative; however, its comparative efficacy remains unclear. This research aimed to directly compare the efficacy and safety of tSNS and topiramate in migraine prevention. In this randomized, open - label, active - controlled trial, 232 adult migraineurs were randomly allocated to either tSNS or oral 25 mg topiramate for a 4 - week duration, followed by an 8 - week follow - up. The primary outcome was the proportion of responders. Secondary outcomes included changes such as monthly migraine days, severe headache days, days of acute medication use, and scores on the Headache Impact Test − 6. Non - inferiority testing with a pre - specified margin of 10% was also performed. The tSNS group exhibited significantly lower responder rates than the low - dose topiramate group (20.6% vs. 33.9%), surpassing the 10% non - inferiority margin (p = 0.712, 95% CI: − 0.260 to − 0.007). Logistic regression affirmed the superior efficacy of 25 mg daily topiramate compared to the tSNS (adjusted OR = 2.32, 95% CI: 1.22–4.42, p = 0.011). When analyzing the secondary outcomes, the tSNS seemed to display efficacy in reducing severe headache days, while topiramate had a more pronounced effect on reducing moderate - severe headache days. In comparison with the tSNS, topiramate showed superior ability in reducing acute medication usage. The Headache Impact Test − 6 scores were comparable between the two groups. The tSNS presented significantly superior safety, with an adverse event rate of 4.3% as opposed to 22.4% in the topiramate group. The tSNS seems to be less effective than even low - dose topiramate in achieving overall migraine prevention. However, the favorable safety profile of tSNS supports its consideration for medication - intolerant patients. NCT02590939: 2022/8/16.