Tiagabine (Gabitril) experience in children

Abstract

Tiagabine (TGB) is indicated as adjunctive therapy for partial seizures in adults and children aged 12 years and older. Double-blind, placebo-controlled studies of TGB treatment are under way in younger children with various forms of epilepsy. The results of pediatric pharmacokinetic trials indicate patterns similar to those seen in adults. An open-label study was conducted in the United States in 31 children with refractory complex partial seizures, with doses escalated every 2 weeks by 0.25 mg/kg up to a maximal daily dose of 1 mg/kg. Twenty-nine patients were treated with TGB for <1 year; 26 completed the study, of whom 18 were receiving monotherapy at study completion. A European dose-escalation study evaluated TGB (0.25-1.5 mg/kg/day) as add-on therapy in 52 children aged 2-15 years. TGB appeared to be more effective in localization-related epilepsy syndromes, with 17 of 23 patients with localization-related epilepsy having a 33% median reduction of seizure rate compared with baseline in the fourth month of treatment, and six patients having ≤50% seizure rate reduction. In this study, myoclonic seizures and spasms showed a poor response as opposed to encouraging findings reported by other groups with these seizure types. The adverse effect profile of TGB in children with epilepsy is similar to that in adults. In the U.S. study, most common adverse events were related to the central nervous system (CNS) and decreased over time. In the European study, mostly mild to moderate adverse events, including asthenia (19%), nervousness (19%), dizziness (17%), and somnolence (17%), were reported by 83% of TGB-treated children (39% of children reported adverse events during the single-blind placebo period). In summary, preliminary pediatric data with TGB suggest particular efficacy against epilepsy characterized by partial seizures or other syndromes, and further investigation is warranted.