Transcranial Direct Current Stimulation Reduces Seizure Frequency in Patients with Refractory Focal Epilepsy: A Randomized, Double-blind, Sham-controlled, and Three-arm Parallel Multicenter Study

Abstract Background Transcranial direct current stimulation (tDCS) has been explored in epilepsy with limited samples, varied parameters, and inconclusive results. We aimed to study the efficacy of tDCS for patients with refractory focal epilepsy. Method We conducted a randomized, double-blind, sham-controlled, and three-arm (Group 1 (sham), Group 2 (20-minutes), and Group 3 (2 × 20-minutes)) tDCS parallel multicenter study. The primary outcome measurement was seizure frequencies (SFs). The study consisted of 28-days baseline, 14-days treatment, and 56-days follow-up. The cathode was placed over the epileptogenic focus, and the current intensity was 2 mA. The generalized estimating equations model, one-way analysis of variance, chi-square and Kruskal-Wallis test were used for analysis. Results Of the 82 enrolled patients, 70 patients were included for final analysis (Group 1, n=21; Group 2, n=24; and Group 3, n=25). There was a significant reduction in SFs for both active tDCS groups compared with the sham group. Patients in Group 2 showed a significantly 50.73–21.91% greater reduction in SFs that lasted for 4 weeks (p = 0.008–0.060). Patients in Group 3 showed a significantly 63.19–49.79% greater reduction in SFs compared with the sham group that lasted for 5 weeks (p = 0.011–0.045). Patients in Group 3 had a 64.98–66.32% greater reduction in SFs at W9–W10, when compared with Group 2 (p = 0.021–0.022). Conclusion Fourteen consecutive days tDCS significantly decreased SFs in patients with refractory focal epilepsy, with 2 × 20-minutes daily stimulation protocol being superior to 20-minutes daily stimulation protocol.