A prospective long-term study of external trigeminal nerve stimulation for drug-resistant epilepsy

Abstract Background External trigeminal nerve stimulation (eTNS) is an emerging noninvasive therapy for drug-resistant epilepsy (DRE). We report the long-term safety and efficacy of eTNS after completion of a phase II randomized controlled clinical trial for drug-resistant epilepsy. Methods This was a prospective open-label long-term study. Subjects who completed the phase II randomized controlled trial of eTNS for DRE were offered long-term follow-up for 1 year. Subjects who were originally randomized to control settings were crossed over to effective device parameters (30 s on, 30 s off, pulse duration of 250 s, frequency of 120 Hz). Efficacy was assessed using last observation carried forward or parametric imputation methods for missing data points. Outcomes included change in median seizure frequency, RRATIO, and 50% responder rate. Results Thirty-five of 50 subjects from the acute double-blind randomized controlled study continued in the long-term study. External trigeminal nerve stimulation was well tolerated. No serious device-related adverse events occurred through 12 months of long-term treatment. At six and twelve months, the median seizure frequency for the original treatment group decreased by -2.39 seizures per month at 6 months (-27.4%) and -3.03 seizures per month at 12 months (-34.8%), respectively, from the initial baseline (p  Conclusion The results provide long-term evidence that external trigeminal nerve stimulation is a safe and promising long-term treatment for drug-resistant epilepsy.