Cognitive and behavioral effects of perampanel 4 mg daily dose.

Objective: The neuropsychological adverse effects of antiseizure medications (ASMs) influence the tolerability, and in turn effectiveness of these medications, which can occur in a dose-dependent fashion. In this study, we examine the neuropsychological effects of perampanel (PER) at 4 mg daily as this dose has not been previously assessed with objective cognitive tests.

Methods: The study was originally designed to assess (1) effects of perampanel at 4 mg using different titration rates, and (2) habituation over time. Due to the COVID-19 pandemic, the study was halted, limiting the sample size needed to analyze titration and habituation effects. Therefore, we compared the neuropsychological effects of perampanel 4 mg daily from non-drug baseline to the end of drug titration and end of drug maintenance in this randomized double-blind study of healthy volunteers. Treatment period was 6 weeks total with 2 weeks of variable titration followed by 4-week maintenance. Composite Z-scores were calculated by combining Z-scores from both cognitive (computerized and non-computerized) and behavioral tests. Secondary analyses were conducted on the independent cognitive and behavioral domain Z-scores, and on the raw scores from 19 items in the full battery.

Results: The overall composite Z-scores did not differ across baseline, the end of titration, and the end of maintenance. Similarly, individual cognitive and behavioral domain Z-scores did not differ across the three titration rates. Exploratory analyses of the raw scores were marginally significant on only two of the 19 neuropsychological measures.

Conclusions: Perampanel 4 mg daily was well tolerated with few neuropsychological effects in healthy volunteers.