Repetitive Transcranial Magnetic Stimulation for the Treatment of Focal Drug-Resistant Epilepsy: A Crossover, Randomized, Single-Blinded, Sham-Controlled Clinical Trial

To evaluate the efficacy and safety of low-frequency repetitive transcranial magnetic stimulation (LF rTMS) in patients with focal drug-resistant epilepsy (DRE) using a randomized, single-blinded, crossover design (NCT06681480 on ClinicalTrials.gov).

Eighteen patients with focal DRE completed two 5-day treatment phases with either active or sham LF rTMS (0.5 Hz, 90 % rMT, 3000 pulses/session), separated by a 3-month washout period. The epileptogenic focus was targeted using MRI-guided neuronavigation. Primary outcomes included monthly seizure frequency, responder and seizure-free rates, and duration of seizure freedom. Secondary outcomes included weekly seizure frequency, interictal epileptiform discharges (IEDs), seizure severity, and quality of life. Crossover-specific analyses were performed with baseline correction.

Active rTMS resulted in a significant reduction in monthly seizure frequency compared to sham (p = 0.0399), with 50 % of patients classified as responders and 16.7 % achieving seizure freedom. The seizure reduction was most prominent during the first two weeks after stimulation. Active rTMS also significantly reduced seizure severity (p < 0.0001) and improved quality of life (p = 0.0212). Although a trend toward reduction in IEDs was observed, this did not reach statistical significance. No serious adverse events occurred, and treatment was well tolerated.

LF rTMS targeting the epileptogenic focus appears to be a safe and potentially effective non-invasive adjunctive therapy for focal DRE. Its short-term efficacy and favorable safety profile support further investigation, including studies incorporating maintenance stimulation protocols and biomarker-guided treatment strategies.