Effectiveness of transcranial direct current stimulation and monoclonal antibodies acting on the CGRP as a combined treatment for migraine (TACTIC): Results of a randomized controlled trial

• Published in: Cephalalgia Vol. 45; no. 5; p. 3331024251325567
• Main Authors: Ornello, Raffaele, D’Atri, Aurora, De Icco, Roberto, De Santis, Federico, Rosignoli, Chiara, Onofri, Agnese, Vaghi, Gloria, Cammarota, Francescantonio, Brancaccio, Carla, Corrado, Michele, Bighiani, Federico, Grillo, Valentina, Sances, Grazia, Corigliano, Domenico, Salfi, Federico, Tassorelli, Cristina, Ferrara, Michele, Sacco, Simona
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.05.2025
• Subjects: Adult; Antibodies, Monoclonal - therapeutic use; Calcitonin Gene-Related Peptide - antagonists & inhibitors; Calcitonin Gene-Related Peptide - immunology; Combined Modality Therapy - methods; Double-Blind Method; Female; Humans; Male; Middle Aged; Migraine Disorders - therapy; Transcranial Direct Current Stimulation - methods; Treatment Outcome; Young Adult; neuromodulation; resistant migraine; migraine; refractory migraine; transcranial direct current stimulation; monoclonal antibodies
• ISSN: 0333-1024; 1468-2982; 1468-2982
• DOI: 10.1177/03331024251325567

Background Migraine pathogenesis involves both central and peripheral mechanisms. Although calcitonin gene-related peptide monoclonal antibodies have shown efficacy over placebo in migraine prevention, a proportion of individuals with migraine may experience a substantial residual burden while on treatment. Transcranial direct current stimulation is a non-invasive neuromodulation technique that can target central migraine mechanisms and may therefore complement calcitonin gene-related peptide monoclonal antibodies. The present study aimed to assess the efficacy of transcranial direct current stimulation as an adjunctive treatment to calcitonin gene-related peptide monoclonal antibodies in migraine prevention and to investigate its neurophysiological effects. Methods This is a multicenter, randomized double-blind, sham-controlled, parallel-group trial including subjects with migraine on treatment with calcitonin gene-related peptide monoclonal antibodies for ≥90 days and with ≥8 monthly migraine days in the last 30 days. Subjects were randomized to active or sham transcranial direct current stimulation. The transcranial direct current stimulation protocol consisted of five daily 20-minute sessions of bilateral cathodal stimulation on the occipital area and anodal stimulation on the M1 area. High-density electroencephalographic recordings were performed before the first and after the last transcranial direct current stimulation session. The primary endpoint was the number of headache days during the 28-day follow-up period controlling for the 28-days baseline value. Secondary endpoints included the number of migraine days during the follow-up period, disability measures and electroencephalographic spectral power. The active and sham groups were compared using analysis of covariance. For clinical outcomes with significant differences between groups, we also ran paired t-tests comparing baseline and follow-up assessment within groups. Results Thirty participants were randomized (15 to active and 15 to sham group). Headache days during the 28-day follow-up period did not differ significantly between groups (p = 0.560, ηp2 = 0.017). However, participants receiving active transcranial direct current stimulation reported fewer migraine days during follow-up compared to the sham group (p = 0.008, ηp2 = 0.241). Paired t-tests indicated that the active tDCS group reported a reduction in migraine days during the follow-up period compared to baseline (t = 2.557, p = 0.023, Cohen's d = 0.660), while no difference was found in the sham group. Referring to neurophysiological endpoints, active transcranial direct current stimulation induced a significant decrease in delta power at frontal regions compared to sham. Conclusions This randomized-controlled trial suggests that transcranial direct current stimulation is a promising potentially effective treatment that may give additional benefits to subjects with migraine who are already on prevention with calcitonin gene-related peptide monoclonal antibodies but who have a substantial residual migraien burden. Combination treatments need to be better explored to provide strategies to further improve benefits of migraine prevention. Trial Registration : NCT05161871 (clinicaltrials.gov). Graphical abstract This is a visual representation of the abstract.