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 refractory partial epilepsy were assessed in a single-blind, add-on, fixed-sequence, placebo-controlled trial. After 1-month observation, the patients entered a 7-month treatment period that involved administration of placebo for 1 month followed by VGB at the initial dosage of 40 mg/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 dropped out prematurely due to lack of efficacy of the drug (n = 6) or increased seizure frequency (n = 1). In 11 patients who either became seizure-free (n = 3) or improved markedly (n = 8), treatment was completed at a dose < 80 mg/kg/day. The average number of seizures per month in the 39 patients who completed the study decreased from 97 during placebo to 21, 12, and 9 after 2, 4, and 6 months of VGB treatments respectively (p < 0.0001 at each time). Response to VGB remained statistically significant when dropouts were included in the evaluation. The number 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 treatment). Serum levels of associated antiepileptic drugs (AEDs) showed no significant changes, except for serum phenytoin (PHT) concentration, which significantly (p < 0.01) decreased after VGB treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Dalla Bernardina
B
B
Cattedra di Neuropsichiatria Infantile, Ospedale Borgo Roma, Verona, Italy.
Fontana
E
E
Vigevano
F
F
Fusco
L
L
Torelli
D
D
Galeone
D
D
Buti
D
D
Cianchetti
C
C
Gnanasakthy
A
A
Iudice
A
A
D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003627:Data Interpretation, Statistical; D004828:Epilepsies, Partial / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D010672:Phenytoin / Q000097:blood; D010919:Placebos; D016037:Single-Blind Method; D013997:Time Factors; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000927:Anticonvulsants; D010919:Placebos; D005680:gamma-Aminobutyric Acid; D010672:Phenytoin; D020888:Vigabatrin