Repetitive transcranial magnetic stimulation as adjunctive therapy in adult patients with drug‐resistant epilepsy—A systematic review and meta‐analysis

Abstract Purpose We performed a comprehensive systematic review and meta‐analysis of repetitive transcranial magnetic stimulation (rTMS) to explore its use as an adjunctive therapy for adult patients with drug‐resistant epilepsy (DRE). Methods Following PRISMA guidelines, PubMed and Ovid MEDLINE databases were searched until January 2025 for English‐language studies reporting pre‐ and post‐rTMS seizure frequencies and detailed protocols in adult patients with DRE. Random‐effects meta‐analyses pooled standardized mean differences in weekly seizure frequency at immediate, 4‐week, and 8‐week follow‐ups. Risk of bias was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools, and evidence certainty was graded using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) and Oxford Centre for Evidence‐Based Medicine (OCEBM) frameworks. Results 12 studies involving 150 participants were included, with seven contributing to the meta‐analysis. Meta‐analysis demonstrated a small but statistically significant reduction in seizure frequency at 4 and 8 weeks following rTMS (pooled SMD −.49 [95% CI −.98 to −.01, p = .46] and −.19 [95% CI −.35 to −.02, p = .91]), with insignificant heterogeneity ( I 2 = 0%). In contrast, no statistically significant difference was observed immediately after rTMS (pooled SMD .19 [95% CI −1.69 to 1.31, p = .38]). Common adverse effects included headaches (14%–33%) and hearing problems (9%–14%). Quality of life improved significantly in two of three studies, and one study reported depression improvement in 67% of participants. Risk of bias was low in three studies, moderate in five, and high in four. Conclusion rTMS use as adjunctive therapy for DRE demonstrated moderate (GRADE level 2) and low‐quality (OCEBM level 3) evidence. rTMS was associated with modest reductions in seizure frequency in selected populations. However, effect sizes were small and heterogeneous. Larger, prospective, multicenter studies are needed to further evaluate its efficacy. Registration International Prospective Register of Systematic Reviews (PROSPERO) (ID #CRD42024553998).