New anti-seizure medication for elderly epilepsy patients - a critical narrative review

ABSTRACT

Introduction: The number of elderly patients with epilepsy is growing in resource rich countries due to demographic changes and increased longevity. Management in these patients is challenging as underlying etiology, co-morbidities, polypharmacy, age-related pharmacokinetic and pharmacodynamic changes need to be considered.

Areas covered: Lacosamide, eslicarbazepine acetate, brivaracetam, and perampanel have been approved in the USA and Europe for monotherapy and/or adjunctive treatment of seizures in the last few years. The authors review the pharmacological properties and safety profile of these drugs and provide recommendations for their use in in the elderly.

Expert opinion: There are only limited data available on more recent antiseizure medications (ASMs). Drugs with a low risk of interaction (lacosamide, brivaracetam) are preferred choices. Once daily formulations (perampanel and eslicarbazepine acetate) have the advantage of increased compliance. Intravenous formulations (brivaracetam and lacosamide) are useful in emergency situations and in patients who have difficulties to swallow. Dose adjustments are necessary for all ASMs used in the elderly with slow titration and lower target doses than in the regulatory trials. The adverse event profile does not significantly differ from that found in the general adult population.

KEYWORDS:

• Antiepileptic drugs
• elderly
• lacosamide
• eslicarbazepine acetate
• brivaracetam
• perampanel

Article highlights

• Pharmacokinetic and pharmacodynamic changes of aging, comorbidities and polypharmacy need to be considered when choosing antiseizure medications (ASMs) in elderly patients.

• Enzyme-inducing ASMs should be avoided in the elderly due to high risk of drug-drug interactions and metabolic derangements.

• The newer ASMs with low drug–drug interaction potential (lacosamide, brivaracetam, and eslicarbazepine acetate) have advantages in the elderly.

• Data on novel ASMs for the treatment of elderly patients is limited as this population is underrepresented in clinical trials.

• Once daily formulations (perampanel, eslicarbazepine acetate) increase compliance; intravenous formulations (brivaracetam, lacosamide) are useful in emergency setting and in patients who are temporarily unable to swallow.

• Dose adjustment with slow titration and low target doses is generally recommended in the elderly to minimize the risk of adverse events.

This box summarizes key points contained in the article.

Declaration of interest

A Rohracher has received travel support and speaker’s honoraria from Eisai while E Trinka has worked as a paid consultant for UCB Pharma, Eisai, Bial, Medtronic, Marinus, Epilog, Everpharma, Biogen Idec, Takeda, Liva-Nova, Newbridge, Sunovion and GW Pharmaceuticals. He has also received research funding (directly and/or via institution) from GlaxoSmithKline, Biogen Idec, Eisai, Novartis, Red Bull, Bayer Healthcare, and UCB. E Trinka has also received speaker’s honoraria from GlaxoSmithKline, Boehringer Ingelheim, Eisai, Bial, Everpharma, UCB, Liva-Nova, Newbridge, Novartis, Epilog, Biogen Idec, and Sanofi. He is also the CEO of Neuroconsult Ges.m.b.H and has received grants from the Austrian Science Fund (FWF), the Osterreichische Nationalbank and the European Union. G Kaiss has received travel support from UCB and Eisai. M Leitinger has meanwhile received speaker’s honoraria from Eisai and Everpharma as well as travel grants from Medtronic and UCB Pharma. Furthermore, S Lattanzi has received speaker’s honoraria or consultancy fees from Eisai, UCB Pharma, and GW Pharmaceuticals and has served on an advisory board for GW Pharmaceuticals. Finally, F Brigo has received speaker’s honoraria from Eisai and Peer Voice as well as payment for consultancy from Eisai and travel support from Eisai, Italfarmaco, and UCB Pharma. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.