Sixty-six children with various types of severe drug-resistant epilepsy were entered into a long-term, dose-rising study of vigabatrin after a 4-week run-in placebo period. All the children were receiving one to three other antiepileptic drugs, the doses of which were not changed during the 6-month dose titration phase. Following the introduction of vigabatrin, 11 patients became seizure free, and 28 responded with a greater than 50% reduction in seizure frequency. The following types of epilepsy responded favorably in order of decreasing efficacy: cryptogenic and symptomatic partial epilepsy, other symptomatic generalized epilepsy, and Lennox-Gastaut syndrome. However, three of nine patients with myoclonic epilepsy showed an increase in seizure frequency. Optimal responses were found with vigabatrin doses of 40 to 80 mg/kg/ day, although no significant adverse effects were noted with doses of higher than 100 mg/kg/day. Thirty-eight responders continued on vigabatrin, 19 of whom have been treated for more than 1 year, with generally good efficacy. As a result of discontinuing concomitant antiepileptics, six patients are on monotherapy with vigabatrin, four of whom are seizure free. Vigabatrin tolerability was good, with 39 of 66 children reporting no adverse effects. Hyperkinesia was reported in 17 patients (26%), and two had to drop out of the study. All these patients had a history of hyperkinesia or mental retardation. In patients in whom vigabatrin dose was reduced because of hyperkinesia, a dose increase could later be instituted without recurrence of symptoms. There was no change in neurologic examination and no drug-related abnormalities in clinical laboratory data. It is concluded that this study shows that vigabatrin is safe and effective in the treatment of refractory epilepsy of various types in children. The recommended starting dose is 40 mg/kg/day, which can be increased up to 80 mg/kg/day, depending on clinical response.
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health
- Clinical Neurology