Evaluating the efficacy of transcranial direct current stimulation for refractory epilepsy: A meta-analysis of RCTs and non-RCTs

An increasing number of research indicate that non-invasive neurostimulation techniques, like transcranial direct current stimulation (tDCS), can effectively control refractory epilepsy. While previous meta-analyses have primarily focused on randomized controlled trials (RCTs), this study expands the scope by including both RCTs and non-RCTs to provide a more comprehensive assessment of tDCS efficacy in treating refractory epilepsy. Through a systematic search of "PUBMED, Embase and Cochrane", we sought relevant studies related to the research topic. We utilized the Cochrane Collaboration tool to assess the risk of bias for the RCTs and the Methodological Index for Non-Randomized Studies (MINORS) tool to evaluate the quality of the non-RCTs included in this meta-analysis. In addition, a protocol for this meta-analysis was registered on PROSPERO (CRD42024496837 http://www.crd.york.ac.uk/ PROSPERO). A total of 14 studies, including 8 RCTs and 6 non-RCTs , involving 307 subjects with refractory epilepsy, were included in this meta-analysis. The combined analysis of RCTs and non-RCTs indicated that tDCS was effective in reducing seizure frequency (SF) in refractory epilepsy patients, with significant improvements observed both four weeks (MD = -4.54; p < 0.01; 95 % CI = -5.69 to -3.38) and eight weeks (MD = -3.49; p < 0.01; 95 % CI = -5.37 to -1.61) after stimulation. There were no statistically significant differences in Interictal Epileptiform Discharges (IEDs) shortly after stimulation (MD = -3.59; p = 0.42; 95 % CI = -12.33-5.16). However, a reduction was observed at four weeks (MD = -5.28; p < 0.01; 95 % CI = -6.88 to -3.68) and eight weeks post-stimulation (MD = -3.37; p < 0.01; 95 % CI = -5.35 to -1.40). The patient's adverse reactions were mild, and they could be relieved shortly after discontinuation of the stimulus. The quality of evidence across outcomes was assessed as moderate. The results indicate that tDCS demonstrates promising efficacy and safety in managing seizures in refractory epilepsy. While this meta-analysis provides valuable findings, additional large-scale randomized controlled trials are needed to further confirm the efficacy of tDCS for refractory epilepsy.