Tiagabine adjunctive therapy in children with refractory epilepsy: a single-blind dose escalating study.
Tiagabine, a specific gamma-aminobutyric acid-uptake inhibitor, has been shown to be reasonably well tolerated and efficacious as adjunctive treatment for partial seizures in adults and is now being investigated in children. This 4-month, single-blind study evaluated the tolerability, safety and preliminary 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 reported by 39% of children during the single-blind placebo period and by 83% of children during tiagabine treatment. The events predominantly affected the nervous system with asthenia (19%), nervousness (19%), dizziness (17%) and somnolence (17%) being 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 syndromes. Twenty-three patients with localisation-related epilepsy syndromes were included and 17 of these patients entered the fourth dosing period. The 17 patients had a median reduction of seizure rate in the fourth month of treatment of 33% compared with baseline. In comparison, 13 of 22 children with 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 resolved. Tiagabine showed efficacy mainly in localisation-related syndromes and was well tolerated by most children in a group of very refractory patients and warrants further study in children with epilepsy.
Uldall
P
P
Dianalund Epilepsy Hospital, Copenhagen, Denmark.
Bulteau
C
C
Pedersen
S A
SA
Dulac
O
O
Lyby
K
K
D000293:Adolescent; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D002648:Child; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy* / Q000523:psychology; D005260:Female; D006801:Humans; D008297:Male; D009557:Nipecotic Acids / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D011446:Prospective Studies; D016037:Single-Blind Method; D000078308:Tiagabine
D000927:Anticonvulsants; D009557:Nipecotic Acids; D000078308:Tiagabine