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Randomized Controlled Trial
. 2025 Mar:164:110268.
doi: 10.1016/j.yebeh.2025.110268. Epub 2025 Jan 16.

Cognitive and behavioral effects of perampanel 4 mg daily dose

Kimford J Meador  1 , Jordan Seliger  2 , Scheherazade Le  3 , Yi Li  4 , Babak Razavi  5 , Jessica Falco-Walter  6 , Alexa King  7 , Edith Graham  8 , Elizabeth Cunningham  9 , Beth Leeman-Markowski  10 , Alan Boyd  11 , David W Loring  12 , Elizabeth Gerard  13
Affiliations
Randomized Controlled Trial

Cognitive and behavioral effects of perampanel 4 mg daily dose

Kimford J Meador et al. Epilepsy Behav. 2025 Mar.

Abstract

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.

Keywords: Adverse effects; Antiseizure medications; Behavior; Cognition; Perampanel.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: KJM has received research support from the National Institutes of Health, VA, Eisai, and Medtronic Inc; the Epilepsy Study Consortium pays his university for his research consultant time in last 3 years related to Eisai, Xenon and UCB Pharma; is Co-I and Director of Cognitive Core of the Human Epilepsy Project for the Epilepsy Study Consortium; is on the editorial boards for Neurology, Cognitive & Behavioral Neurology, Epilepsy & Behavior, and Epilepsy & Behavior Case Reports. JS has no disclosures. SL has no disclosures. YL receives research support from Stanford Maternal and Child Health Research Institute and American Epilepsy Society. BR receives research support from Neuropace and holds stocks in Cortexxus. JFW has no disclosures. AK has no disclosures. ELG has received research support from F. Hoffman La-Roche Ltd and consultancy fees from Novartis, Horizon Therapeutics, Roche/Genentech, and EMD Serono. EC has no disclosures. BLM receives research support from the US Department of Veterans Affairs Clinical Science Research and Development Service. AB is CEO of CNS Vital Signs and was available to consult and respond to any question regarding the cognitive testing platform. DWL has received research support from the National Institutes of Health, salary support from the Georgia Department of Human Services, and stipends for his editorial responsibilities for Neuropsychology Review and Epilepsia.EEG has served as site PI for a clinical trial sponsored by Xenon and serves on the clinical advisory board Xenon. She receives royalties from UpToDate.

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