Noninvasive vagus nerve stimulation for migraine: a systematic review and meta-analysis of randomized controlled trials

BACKGROUND: Medication is commonly used to treat migraine. However, patients may experience adverse events or fail to respond to medication. In recent years, neuromodulation techniques have emerged as potential non-pharmacological therapy for migraine. This article focuses on a systematic review and meta-analysis of randomized controlled trials of non-invasive vagus nerve stimulation (n-VNS) for migraine to determine the efficacy, safety and tolerability of n-VNS. METHODS: We searched PUBMED, EMBASE, and Cochrane Center Register of Controlled Trials databases up to July 15, 2022. Primary outcomes were monthly reduced migraine/headache days, and pain-free rates within 2 h. Secondary outcomes were ≥ 50% responder rate, headache intensity, monthly acute medication reduction days, and adverse events. RESULTS: Meta-analysis shows that non-invasive cervical vagus nerve stimulation (n-cVNS) significantly impacted ≥50% responder rate (OR, 1.64; 95% CI, 1.1 to 2.47; p = 0.02), but had no significant effect on reducing migraine days (MD, −0.46; 95% CI, −1.21 to 0.29; p = 0.23) and headache days (MD, −0.68; 95% CI, −1.52 to 0.16; p = 0.11). In contrast, low-frequency non-invasive auricular vagus nerve stimulation (n-aVNS) was found to significantly reduce the number of migraine days (MD, −1.8; 95% CI, −3.34 to −0.26; p = 0.02) and headache intensity (SMD, −0.7; 95% CI, −1.23 to −0.17; p = 0.009), but not the number of acute medication days per month (MD, −1.1; 95% CI, −3.84 to 1.64; p = 0.43). In addition, n-cVNS was found safe and well-tolerated in most patients. CONCLUSION: These findings show that n-VNS is a promising method for migraine management.