Transcranial direct current stimulation added to CGRP monoclonal antibody therapy significantly reduced migraine days in patients with residual migraine burden, though total headache days were not significantly different.
p=0.008 for migraine day reductionActive brain stimulation significantly reduced migraine days compared to sham when added to CGRP antibody therapy, with a large effect size (ηp²=0.241).
What the researchers found
Active tDCS significantly reduced migraine days compared to sham during the 28-day follow-up (p = 0.008, large effect size ηp² = 0.241). The active group showed a within-group reduction from baseline (Cohen's d = 0.660, p = 0.023), while the sham group did not. However, total headache days did not differ significantly between groups (p = 0.560). Neurophysiologically, active tDCS decreased delta power at frontal brain regions compared to sham, suggesting modulation of central mechanisms.
Why it matters
CGRP-targeting drugs are highly effective for migraine prevention, but a significant proportion of patients retain a substantial migraine burden. This trial demonstrates that combining CGRP antibodies (targeting peripheral peptide pathways) with brain stimulation (targeting central mechanisms) can provide additional relief, supporting a multi-modal approach to migraine management that addresses different parts of the disease pathway.
How the study worked
Multicenter, randomized, double-blind, sham-controlled, parallel-group trial (NCT05161871). 30 migraine patients on CGRP monoclonal antibodies for ≥90 days with ≥8 monthly migraine days were randomized to active or sham tDCS (15 per group). The protocol consisted of five daily 20-minute sessions with bilateral cathodal stimulation on the occipital area and anodal stimulation on M1. High-density EEG was recorded before and after treatment. Primary endpoint: headache days during 28-day follow-up. Analysis of covariance compared groups.
What this study cannot tell us
The sample size is very small (n=30, 15 per group), limiting statistical power and generalizability. The distinction between significant reduction in migraine days but not headache days is puzzling and may reflect the small sample. The 28-day follow-up is short, and durability of the combined effect is unknown. The tDCS protocol was brief (5 sessions), and longer courses might show different results.
How to read the evidence
This is a randomized, double-blind, sham-controlled trial — the gold standard design — but the very small sample size (n=30) significantly limits the strength of conclusions. The findings are promising but need replication in a larger trial.
When this study was published
Published in 2025, this is among the first randomized trials to test combination therapy with CGRP antibodies and neuromodulation, addressing a cutting-edge question in migraine treatment.
The bigger picture
This study exemplifies the evolving approach to migraine treatment: combining peripherally-acting CGRP peptide therapies with centrally-acting neuromodulation. As understanding of migraine grows, it's becoming clear that addressing only the peptide (peripheral) component isn't enough for all patients. Multi-modal approaches that target both the CGRP pathway and central brain mechanisms may become standard care for treatment-resistant migraine.
Questions still open
- Would a longer course of tDCS sessions produce more robust reductions in both migraine and headache days?
- Which CGRP antibody was used, and does the combination work equally well with different CGRP-targeted drugs?
- Could tDCS replace CGRP antibodies in some patients, or is it only effective as an add-on?
Common questions
What is transcranial direct current stimulation (tDCS)?
Why did brain stimulation help even though patients were already on CGRP drugs?
Read the original research
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.
Cephalalgia : an international journal of headache, 45(5), 3331024251325567
Citation
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. (2025). 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.. Cephalalgia : an international journal of headache, 45(5), 3331024251325567. https://doi.org/10.1177/03331024251325567