Old drugs, new indications: Effectiveness of amantadine for epileptic encephalopathy in paediatric patients with spike-wave activation in sleep or refractory absence seizures.

INTRODUCTION: Previous research suggests that amantadine could be effective as an antiepileptic drug. We evaluate the use of the drug in children with refractory generalised epilepsy.

METHOD: Retrospective study of children with developmental and/or epileptic encephalopathy with spike-and-wave activation in sleep (D/EE-SWAS) or generalised epilepsy with refractory absence seizures treated with amantadine at a paediatric hospital in Madrid, Spain, over a 3-year period.

RESULTS: We studied 12 children treated with amantadine for refractory epilepsy at a median age of 9.5 years (range, 3-11) and a median disease duration of 5 years (range, 1-8). Before initiation of amantadine, the patients had received 9.4 antiepileptic drugs on average (range, 6-14), and 9 had been placed on a ketogenic diet. Brain MRI displayed no structural lesion in any patient, except for one with a thalamic lesion. All patients had idiopathic epilepsy, and MRI results were normal. Five were diagnosed with D/EE-SWAS, and 7 had generalised epilepsy with refractory absence seizures (5 with refractory absence epilepsy, one with eyelid myoclonia with absence seizures, and one with Lennox-Gastaut syndrome). Amantadine was added to other antiepileptic drugs (mean number of drugs administered, 2.7) at a mean dose of 5.6mg/kg/day, with a maximum dose of 300mg/day. In the group with D/EE-SWAS, amantadine therapy achieved EEG activity normalisation and seizure control (myoclonic and absence seizures) in 80% (4/5). Among the patients with refractory epilepsy, only one (14.2%) achieved seizure control (75-99% response). One patient (10%) developed adverse effects (irritability and insomnia), leading to withdrawal of amantadine.

CONCLUSION: Amantadine is an effective and safe treatment for drug-resistant generalised epilepsy, especially in patients with D/EE-SWAS.