Timing use of novel anti-epileptic drugs: is earlier better?

ABSTRACT

Introduction: Epilepsy is one of the most common neurological disorders. The goal of pharmacologic therapy remains complete freedom from seizures with minimal side effects. Despite advancements and the development of third-generation antiepileptic drugs (AEDs), a third of patients with epilepsy remain refractory to pharmacotherapy.

Areas covered: The present manuscript is based on an extensive Internet and PubMed search from 2004 to 2019. It is focused on the third-generation AEDs (e.g. lacosamide, eslicarbazepine, perampanel, and brivaracetam).

Expert opinion: Newer antiepileptic drugs are increasingly used. However, how early in the course of epilepsy third-generations AEDs should be used is still unclear. Third-generation AEDs may offer better tolerability, milder adverse effects, less drug interactions and improved pharmacokinetic characteristics compared to the conventional AEDs. For this reason, the third-generation AEDs may be used earlier and earlier in epileptic patients. Further head-to-head comparisons are needed to determine the exact position of third-generation AEDs relative to conventional AEDs.

KEYWORDS:

• Brivaracetam
• efficacy
• eslicarbazepine
• lacosamide
• partial-onset seizures
• perampanel
• pharmacokinetic
• primary generalized tonic–clonic seizures
• toxicology

Article highlights

• The goal of pharmacologic therapy remains complete freedom from seizures with minimal side effects

• Despite advancements and the development of third-generation AEDs, a third of patients with epilepsy remain refractory to pharmacotherapy

• New AEDs usually share many of the pharmacokinetic characteristics of an ideal AED

• The third-generation AEDs have several significant advantages including reduced drug-drug interactions, less life-threatening adverse events and less negative impact on cognitive functions

• There is no evidence that any new AED is more effective than conventional AEDs

• There are a limited number of direct comparisons between old and third-generation AEDs. Further head-to-head comparisons are needed

• Goals of future drug development in epilepsy disorders should target specific types of seizures or epilepsy

• Targeting refractory or pharmacoresistant forms of epilepsy remains an unmet challenge

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded