Tiagabine adjunctive therapy in children with refractory epilepsy: a single-blind dose escalating study

Tiagabine, a specific gamma -aminobutyric acid-uptake inhibitor, has been s hown to be reasonably well tolerated and efficacious as adjunctive treatmen t for partial seizures in adults and is now being investigated in children. This 4-month, single-blind study evaluated the tolerability, safety and pr eliminary efficacy of ascending doses (0.25-1.5 mg/kg/day) of tiagabine add -on therapy in 52 children over the age of 2 years with different syndromes of refractory epilepsy. Adverse events, mostly mild to moderate, were repo rted by 39% of children during the single-blind placebo period and by 83% o f children during tiagabine treatment. The events predominantly affected th e nervous system with asthenia (19%), nervousness (19%), dizziness (17%) an d somnolence (17%) bring the most common. Only three children (6%) withdrew because of adverse events. Tiagabine: appeared to reduce seizures more in localisation-related epilepsy syndromes than in generalised epilepsy syndro mes. Twenty-three patients with localisation-related epilepsy syndromes wer e included and 17 of these patients entered the fourth dosing period. The 1 7 patients had a median reduction of seizure rate in the fourth month of tr eatment of 33% compared with baseline. In comparison, 13 of 22 children wit h seven different generalised epilepsy syndromes entered the fourth dosing period with a median change of seizure rate of 0%. Two patients experienced single episodes of status epilepticus during treatment; both cases resolve d. Tiagabine showed efficacy mainly in localisation-related syndromes and w as well tolerated by most children in a group of very refractory patients a nd warrants further study in children with epilepsy. (C) 2000 Elsevier Scie nce B.V. All rights reserved.