Effectiveness of Transcranial Direct Current Stimulation and Monoclonal Antibodies Acting on the CGRP as a Combined Treatment for Migraine

Background: Migraine is a recurring headache disorder with an unclear pathophysiology involving the central and peripheral nervous systems. Monoclonal antibodies targeting the calcitonin gene-related pathway (CGRP-MAbs) are designed specifically for migraine, acting peripherally on the trigeminal ganglion. In contrast, neuromodulation techniques like transcranial direct current stimulation (tDCS) act centrally by influencing cortical neuronal firing rates. This study aims to assess whether tDCS, when combined with CGRP-MAbs, effectively reduces migraine frequency, intensity, and medication use. Methods: Our study is a randomized, double-blind, multicenter, sham-controlled trial including patients with migraine in CGRP-Mabs treatment with residual monthly migraine days (MMDs) ≥8. After 5-day of tDCS bilateral occipital cathodal and frontal anodal stimulation (sham/active sessions lasting 20 minutes) We closely monitored patients for 28 days, assessing changes in monthly migraine days and clinical scales such as MIDAS, HIT6, HADS. We analyzed the change in migraine days and clinical scales using two-way mixed-design ANCOVAs, with Session (baseline vs. follow-up) as the within-subjects factor and Treatment (Sham vs. Active) as the between-subjects factor. Based on previous literature, a between-groups mean difference of 3 ± 2 migraine days per month was deemed significant. To account for possible dropouts, we set the population size to 30 patients, 15 per group. Results: We included 29 patients (mean age 46±11.5 years, 82.8% female), with 15 in the active session and 14 in the sham group. At baseline, the active group reported a mean of 13.20±6.16 MMDs, while the sham group reported 17.38±7.71 MMDs. tDCS led to a significant reduction in MMDs in the active group (mean 10.10±1.25) compared to the sham group (mean 15.38±1.29; p=0.008). Additionally, a significant improvement was observed in the HIT-6 scale for both the active (p=0.005) and sham (p=0.003) groups. Conclusions: tDCS, as add-on therapy to CGRP-Mabs, exerts a significant effectiveness to MMDs reduction. The observed benefits suggest that integrating tDCS with CGRP-MAbs could offer a more comprehensive and effective management strategy for individuals suffering from chronic migraines. Further research is warranted to fully understand the underlying mechanisms and long-term effects of this combined therapy.