Citation

Chung S, Williams B, Dobrinsky C, Patten A, Yang H, Laurenza A. Epilepsy Behav. 2017; 75: 79-85.

Affiliation

Eisai Neurology Business Group, Eisai Inc., 155 Tice Blvd., Woodcliff Lake, NJ 07677, USA. Electronic address: Antonio_Laurenza@eisai.com.

Copyright

(Copyright © 2017, Elsevier Publishing)

DOI

10.1016/j.yebeh.2017.06.038

PMID

28830031

Abstract

In 4 Phase III registration trials (3 in patients with partial seizures, N=1480; 1 in patients with PGTCS, N=163), perampanel administered to patients already receiving 1-3 concomitant antiepileptic drugs (AEDs) demonstrated statistically superior efficacy compared to placebo in reducing seizure frequency. However, use of perampanel in these studies was associated with a risk of psychiatric and behavioral adverse reactions, including aggression, hostility, irritability, anger, and homicidal ideation and threats. The present study is a post hoc analysis of pooled data from these 4 trials to determine if concomitant treatment with levetiracetam and/or topiramate increased the risk of hostility- and aggression-related AEs. Treatment-emergent AEs (TEAEs) were determined using a "Narrow & Broad" search based on the Medical Dictionary for Regulatory Activities (MedDRA) standard MedDRA query (SMQ) for hostility- and aggression-related events. The rate of hostility- and aggression-related TEAEs was observed to be similar among perampanel-treated patients: a) receiving levetiracetam (N=340) compared to those not receiving levetiracetam (N=779); b) receiving topiramate (N=223) compared to those not receiving topiramate (N=896); and c) receiving both levetiracetam and topiramate (N=47) compared to those not receiving levetiracetam and topiramate (N=1072). Severe and serious TEAEs related to hostility and aggression were rare and occurred at a similar rate regardless of concomitant levetiracetam and/or topiramate therapy. Taken together, these results suggest that concomitant treatment with levetiracetam and/or topiramate has no appreciable effect on the occurrence of hostility- or aggression-related TEAEs in patients receiving perampanel.

Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Language: en

Keywords

Aggression; Epilepsy; Hostility; Levetiracetam; Perampanel; Topiramate