Therapeutic approach to difficult-to-treat typical absences and related epilepsy syndromes

ABSTRACT

Introduction: typical absences (TAs), are brief, generalized epileptic seizures of abrupt onset and termination clinically manifesting with impairment of awareness and associated with 3 Hz spike-wave discharges on EEG. TAs may occur in different idiopathic generalized epilepsies (IGE). Despite treatment with adequate anti-seizure medications (ASMs), TAs may persist in ~25% of subjects. This narrative review focuses on the therapeutic approach to difficult-to-treat TAs occurring in the setting of IGE.

Areas covered: a literature search was conducted on the topic of treatment of TAs.

Expert opinion: ethosuximide (ESX), valproic acid (VPA) and lamotrigine (LTG), alone or in combination, are considered the first-choice drugs. In women of childbearing potential, VPA should be avoided. Alternative therapies (benzodiazepines, levetiracetam, topiramate, or zonisamide) should be considered in subjects unresponsive to monotherapy after the exclusion of pseudo-drug resistance. Newer ASMs such as brivaracetam and perampanel seem to be promising options. Well-conducted clinical trials aimed to evaluate the efficacy of alternative monotherapy (beyond ESX, VPA or LTG) or combination of ASMs on difficult-to-treat TAs, are warranted.

KEYWORDS:

• Idiopathic generalized epilepsy
• childhood absence epilepsy
• juvenile absence epilepsy
• juvenile myoclonic epilepsy
• refractory

Article highlights

• Typical absence seizures are a common seizure type that can occur in various epilepsy syndromes including Childhood Absence Epilepsy or Juvenile Absence Epilepsy.

• Typical absences are considered pharmaco-responsive. However, about 25% of subjects do not respond adequately to treatment.

• Ethosuximide, valproic acid, and lamotrigine, alone or in combination, are considered the drugs of choice.

• Add-on treatment with benzodiazepines, levetiracetam, topiramate, or zonisamide should be considered in subjects unresponsive to monotherapy.

• Well-conducted clinical trials aimed to evaluate the efficacy of alternative monotherapy (beyond ethosuximide, valproic acid or lamotrigine) or combination therapy on difficult-to-treat typical absences, are warranted.

Declaration of interest

E Ferlazzo has received speaking honoraria from EISAI, UCB and Arvelle Therapeutics. E Russo has received speaker fees or funding from, and has participated in advisory boards for Angelini, Arvelle Therapeutics, EISAI, Kolfarma, Pfizer, GW Pharmaceuticals, UVB and Lundbeck. 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 relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.