Abstracts

Rationale: External Trigeminal Nerve Stimulation (eTNS) is an emerging neuromodulation therapy, with positive results from open-label trials in drug resistant epilepsy (DRE) and major depressive disorder (MDD). The purpose of this study is to explore the efficacy of eTNS on seizure frequency and mood in patients with DRE using a randomized double-blind active controlled trial (RCT) design, and to examine parameters and procedures in preparation for a phase III multicenter clinical trial. Methods: Randomized double-blind active-control study in DRE. Subjects with two or more complex-partial or tonic-clonic seizures per month entered a 6-week baseline, and then were evaluated at 6, 12 and 18 weeks during the acute treatment period. Subjects were randomized to active treatment (eTNS, 120 Hz) or control (eTNS, 2 Hz). Results: At entry, subjects had highly refractory epilepsy, averaging 8.7 seizures per month in the active treatment group. Subjects randomized to the active treatment group experienced a significant improvement in the responder rate (RR) during the acute treatment period (RR = 40.5% at 18 weeks versus 17.8% at 6 weeks, p=0.01, GEE logistical model). Over the entire 18-week treatment period, the active treatment group experienced a significant reduction in seizure frequency as measured by the RRATIO (p= 0.04, ANOVA). Furthermore, active treatment was associated with an early and significant improvement in mood as measured by the Beck Depression Inventory (BDI). Conclusions: This phase II trial provides evidence using a RCT design that eTNS may be safe and effective in subjects with DRE. eTNS was associated with significant improvements in responder rate and mood in subjects with DRE. These results will serve as a basis to inform and power a large multicenter phase III clinical trial. The development of a new non-invasive therapy for DRE which significantly improves seizures and mood represents a major advance in the treatment of epilepsy. Trigeminal Nerve Stimulation is an Investigational device. Limited by Federal (or United States) law to investigational use.