Effectiveness and Acceptability of Noninvasive Brain and Nerve Stimulation Techniques for Migraine Prophylaxis: A Network Meta-Analysis of Randomized Controlled Trials

Background: Current pharmacologic prophylactic strategies for migraine have exhibited limited efficacy, with response rates as low as 40%–50%. In addition to the limited efficacy, the acceptability of those pharmacologic prophylactic strategies were unacceptable. Although noninvasive brain/nerve stimulation strategies may be effective, the evidence has been inconsistent. The aim of this network meta-analysis (NMA) was to compare strategies of noninvasive brain/nerve stimulation for migraine prophylaxis with respect to their effectiveness and acceptability. Methods: The PubMed, Embase, ScienceDirect, ProQuest, ClinicalTrials.gov, ClinicalKey, Cochrane CENTRAL, Web of Science, and ClinicalTrials.gov databases were searched for randomized controlled trials (RCTs). Patients with diagnosis of migraine, either episodic migraine or chronic migraine, were included. The primary outcome was the changes in monthly migraine days and response rate, and the acceptability was defined as the drop-out rate. All NMA procedures were conducted under the frequentist model. Findings: Nineteen randomized controlled trials were included (N=1493; mean age=38.2 years; 82.0% women). We determined that the high frequency repetitive transcranial magnetic stimulation (rTMS) over C3 yielded the most decreased monthly migraine days among all the interventions [mean difference=-8.70 days, 95% confidence intervals (95%CIs): -14.45 to -2.95 compared to sham/control groups]. In addition, high-frequency (100 Hz) transcutaneous occipital nerve stimulation (tONS) over the Oz provided the highest response rate in migraine prophylaxis [rate ratio (RR)=9.00, 95%CIs: 1.24 to 65.16 compared to sham/control groups]. Only alternative frequency (2/100 Hz) tONS over the Oz (RR=0.36, 95%CIs: 0.16 to 0.82) yielded a significantly lower drop-out rate than the sham/control groups did. Interpretation: The current study provided a new direction for the design of more methodologically robust and larger RCTs based on the findings of the potentially beneficial effect on migraine prophylaxis in participants with migraine by different noninvasive brain/nerve stimulation, especially the application of rTMS and tONS. Funding Information: None. Declaration of Interests: The authors report no financial interests or potential conflicts of interest.