Randomized phase III study 306: adjunctive perampanel for refractory partial-onset seizures.

OBJECTIVE: To evaluate the efficacy and safety of perampanel 2, 4, and 8 mg/day added to 1-3 concomitant antiepileptic drugs (AEDs) in patients with uncontrolled partial-onset seizures. METHODS: During this double-blind, placebo-controlled trial, patients with persisting seizures on 1-3 AEDs were randomized to perampanel 2, 4, and 8 mg/day or placebo following a 6-week baseline phase. Perampanel was titrated weekly by 2 mg/day and maintained at the dose achieved for 13 weeks. Primary endpoints were median percent change in seizure frequency and 50% responder rate. Analysis of covariance was performed on all treated patients with any seizure data (recorded in daily diaries) in the double-blind phase. RESULTS: A total of 706 patients were randomized and received trial medication; 623 completed the trial. Median percent change in seizure frequency-the primary efficacy endpoint-was -10.7%, -13.6%, -23.3%, and -30.8% for placebo, perampanel 2, 4, and 8 mg/day, respectively. The difference from placebo was statistically significant for perampanel 4 mg/day (p = 0.0026) and 8 mg/day (p < 0.0001). The corresponding 50% responder rates were 17.9%, 20.6%, 28.5%, and 34.9%. The difference from placebo was statistically significant for perampanel 4 mg/day (p = 0.0132) and 8 mg/day (p = 0.0003). An apparent dose response was suggested for dizziness, which was the most frequent treatment-emergent adverse event. CONCLUSIONS: This trial demonstrated that adjunctive perampanel effectively reduced seizure frequency and possessed a favorable tolerability profile in patients ≥12 years with partial-onset seizures (with or without secondary generalization), with a minimum effective dose of 4 mg/day. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that 4 and 8 mg/day doses of adjunctive perampanel are effective and tolerated in reducing partial-onset seizures.

Prevalence of childhood epilepsy in Kaunas, Lithuania.

The prevalence of epilepsy in children aged 0-15 years of Kaunas city, Lithuania, was evaluated on 1 January 1995. Multiple sources for case identification were used, i.e. medical records at the university hospital, regional outpatient clinics and consultation centres, institutions, schools and kindergartens for the handicapped. Active epilepsy was defined as two or more unprovoked epileptic seizures with at least one seizure occurring within the previous 5 years, regardless of the antiepileptic drug treatment. Prevalence was found to be 4.25 (3.42, if age-standardized) in 1000. The highest rate was found in the 10-14 years age group. The male/female ratio was 1.29. No possible causes could be determined in 60.3% of cases. Congenital causes were diagnosed in 18.8% of cases, perinatal causes in 15.3%, traumatic causes in 2.6% and neuroinfectious causes in 2.4%. Classification of epilepsies and epileptic syndromes [Commission on Classification and Prognosis of the International League Against Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 1989; 30:389-399] revealed that 50% of cases were localization-related epilepsies, 29.9% were generalized epilepsies, 15.9% were undetermined whether partial or generalized and 4.2% were unclassifiable. Rates for idiopathic, symptomatic and cryptogenic cases are presented.