Abstracts

Rationale: Perampanel (PER) is the first non-competitive selective antagonist to the postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor received regulatory approval for seizure control. Because of its novel mechanism of action and effectiveness to control both focal and generalized onset seizures, it is now widely used for treatment in patients with refractory epilepsy. However, adverse events (AEs), especially psychiatric and behavior AEs, is one of the main reason for the withdrawal of PER. Slow titration of PER has been suggested by several experts to decrease AEs, but real-world studies showed inconsistent results. More data is required to validate the effect of slow titration of PER to decrease AEs. Methods: We retrospectively collected subjects who received adjunctive PER therapy for refractory epilepsy between December 2015 and July 2017 from the electronic medical record database of Chang Gung Memorial Hospital, Taiwan. These subjects were categorized as fast-titration (an increase of dose greater than or equal to 4 mg in 4 weeks) or slow-titration (an increase of dose less than 4 mg in 4 weeks) according to their titration schedule at the initial three months of PER administration. Seizure control, adverse events (AE), withdrawal rates, and the maximum tolerated dose of PER were compared between these two groups. Results: Totally 158 patients were included for analysis. Ninety-eight patients were categorized as fast-titration, and 60 patients were slow-titration. The mean follow-up was 10.3 months (range 1-13). Fast-titration group had significantly more total AEs (56.1% versus 38.3%, p=0.03) and neurologic AEs (34.7% versus 20.0%, p=0.048) compared to slow-titration group. Among neurologic AEs, dizziness was the most commonly reported (20.9%) and was significantly more frequent in the patients who received fast titration. The withdrawal rate was numerically higher in the fast-titration group (41.8% versus 30.0%). Furthermore, the maximum tolerated dose of PER was significantly higher for the slow-titration group (fast-titration group: 5.94±2.93mg/day, slow-titration group: 6.90±2.59mg/day, p=0.023). Conclusions: Titration of PER less than 4mg per 4weeks at the first three months helps to decrease neurologic AEs and may increase the maximum tolerated dose for patients receiving adjunctive PER therapy for refractory epilepsy. Further studies examining tolerability, AEs, and effectiveness of seizure control at different titration speed will help to find the optimal titration schedule in patients receiving PER. Funding: No funding