ADJUVANT VIGABATRIN IN REFRACTORY EPILEPSY - A CEILING TO EFFECTIVE DOSAGE IN INDIVIDUAL PATIENTS

A double-blind, randomized, cross-over study of additional vigabatrin (gamma-vinyl-GABA, VGB, 1.0 g twice daily for 6 weeks, followed by 1.5 g twice daily for 6 weeks) and matched placebo was undertaken in 24 p atients with refractory epilepsy. Nineteen completed the trial satisfa ctorily. Fewer seizure days were reported during VGB treatment [placeb o 41, VGB 23, p < 0.05, 95% confidence interval (CI) - 1.5 to - 14]. A n overall reduction in median seizure numbers failed to reach statisti cal significance (n = 19; placebo 52, VGB 32, NS, 95% CI - 18 to + 24) . Subgroup analysis, however, showed a significant reduction in partia l seizures (n = 17) with 2 g VGB daily (placebo 22, VGB 13, p < 0.05, 95% CI - 0.5 to - 16.5), but not with higher dosage (placebo 28, VGB 2 2, NS, 95% CI - 18 to + 11). A deterioration in control of partial sei zures as compared with the equivalent placebo phase was observed when patients were changed from 2 to 3 g/day VGB (2 g VGB 13, 3 g VGB 22, p = 0.05, 95% CI 0 to + 20). Loss of efficacy was noted in 3 patients, and seizure control worsened slightly in 5 others. One previously resi stant patient developed a therapeutic response, and 2 other patients r eported an additional useful reduction in seizures. In the remaining 8 patients, seizure frequency did not change. VGB did not appear to ben efit tonic-clonic seizures. Serum VGB concentrations were higher durin g treatment with 3 g (15.5 +/- 8.9 mg/L) daily than with 2 g (13.5 +/- 11.2 mg/L). No important alterations were noted in the concentrations of concomitantly administered antiepileptic drugs (AEDs) throughout t he trial. VGB is useful adjuvant therapy for treatment of partial seiz ures. There may be a ceiling to effective dosage. This demands individ ual dose titration for each patient.