Comparative Efficacy of Interventions for Drug-Resistant Epilepsy: A Network Meta-analysis

Background Drug-resistant epilepsy remains difficult to manage when medications and surgical resection are ineffective or unsuitable. Several neurostimulation approaches are now used as alternative treatments, yet their comparative effectiveness has not been clearly established. Methods A systematic search of PubMed، Web of Science، and Scopus identified 435 studies, of which 16 randomized or quasi-randomized controlled trials fulfilled eligibility criteria for inclusion in a network meta-analysis. The primary outcome was the proportion of participants achieving at least a 50 percent reduction in seizure frequency. A random-effects network meta-analysis integrated direct and indirect evidence, with assessment of heterogeneity, global and local inconsistency, and potential small-study effects. Study quality was evaluated using the Newcastle–Ottawa Scale. Results The network showed high coherence with minimal inconsistency. Noninvasive methods particularly repetitive transcranial magnetic stimulation، transcranial direct current stimulation، and external trigeminal nerve stimulation produced the strongest seizure-reduction effects. Deep brain stimulation and vagus nerve stimulation offered moderate but consistent benefits, while responsive neurostimulation showed weaker short-term efficacy within the limited randomized evidence. Precision for several modalities remained constrained by the small number of eligible trials. Conclusion This analysis provides an integrated comparison of neurostimulation approaches for drug-resistant epilepsy and highlights the promising therapeutic potential of several noninvasive modalities. Larger randomized studies with standardized stimulation parameters, extended follow-up, and mechanistic biomarkers are needed to refine treatment selection and optimize long-term clinical outcomes.