EFFICACY AND TOLERABILITY OF VIGABATRIN IN CHILDREN WITH REFRACTORY PARTIAL SEIZURES - A SINGLE-BLIND DOSE-INCREASING STUDY

The efficacy and tolerability of vigabatrin (VGB) in children with ref ractory partial epilepsy were assessed in a single-blind, add-on, fixe d-sequence, placebo-controlled trial. After 1-month observation, the p atients entered a 7-month treatment period that involved administratio n of placebo for 1 month followed by VGB at the initial dosage of 40 m g/kg/day, to be increased to 60 and 80 mg/kg/day at 2-month intervals if seizures persisted. Of the 46 children enrolled in the study, 7 dro pped out prematurely due to lack of efficacy of the drug (n = 6) or in creased seizure frequency (n = 1). In 11 patients who either became se izure-free (n = 3) or improved markedly (n = 8), treatment was complet ed at a dose <80 mg/kg/day. The average number of seizures per month i n the 39 patients who completed the study decreased from 97 during pla cebo to 21, 12, and 9 after 2, 4, and 6 months of VGB treatments respe ctively (p < 0.0001 at each time). Response to VGB remained statistica lly significant when dropouts were included in the evaluation. The num ber of patients who had >50% reduction in Seizure frequency after 2, 4 , and 6 months was 28, 33, and 35, respectively. Eight patients became seizure-free during the last 2 months of VGB treatment (3 at 40, 3 at 60, and 2 at 80 mg/kg/day, as compared with none during placebo treat ment). Serum levels of associated antiepileptic drugs (AEDs) showed no significant changes, except for serum phenytoin (Pi-IT) concentration , which significantly (p < 0.01) decreased after VGB treatment. Increa sed appetite and sedation were observed in 17 and 11% of cases, respec tively. VGB is effective in the management of refractory partial epile psy in children, and in some patients a positive dose-response relatio nship appears to occur over the assessed dosing range.