Effectiveness of neuromodulation techniques for migraine prophylaxis: a systematic review and network meta-analysis of randomized controlled trials

Given limited efficacy and potential complications of pharmacological approaches, neuromodulation techniques are emerging as non-pharmacological alternatives for migraine prevention. The present study aimed to conduct a systematic review and network meta-analysis to compare the effectiveness of neurostimulation interventions for migraine prophylaxis. The PubMed/MEDLINE, Cochrane, Web of Science, Embase, Clinicaltrials.gov, China National Knowledge Infrastructure, Chongqing VIP, Wanfang, Chinese Biomedical Literature Database, Chinese Clinical Trial Registry, and International Traditional Chinese Medicine Clinical Trial Registry databases were systematically searched up to February 7th, 2025 for randomized controlled trials (RCTs). Outcomes of interest were changes in monthly migraine days, response rate and changes in pain intensity. Network meta-analyses were based on a Bayesian framework. Forty RCTs (N = 4341; mean age = 38.7 years; % females = 81.2) were included in the network meta-analysis. Transcranial magnetic stimulation (TMS), transcranial electrical stimulation (tES), percutaneous mastoid electrical stimulation (PMES), supraorbital transcutaneous stimulation (STS), and acupuncture were associated with significant improvements in migraine frequency, response rate and pain severity. Both invasive and non-invasive occipital nerve stimulation (ONS) demonstrated significantly higher response rates relative to sham controls. Among all the investigated interventions, tES (SUCRA = 82%; SMD = 0.9; 95% CrI = 0.32, 1) yielded the greatest reduction in monthly migraine days, transcutaneous ONS (tONS) (SUCRA = 90%; RR = 12; 95% CrI = 1.9, 389) exhibited the highest response rate, and PMES (SUCRA = 96%; SMD = 2.4; 95% CrI = 0.75, 3.4) yielded the most decreased pain intensity after intervention. The main findings of this study highlight the beneficial effect of tES and tONS in reducing migraine frequency and improving treatment response, respectively. Due to scanty evidence for certain interventions and network model limitations, caution is needed when interpreting the results. Future large-scale and well-conducted RCTs are required to strengthen the reliability and validity of the findings. The study protocol was registered on the International Prospective Register of Systematic Reviews. Registration Number: CRD42025642688.