Adjuvant Vigabatrin in Refractory Epilepsy: A Ceiling to Effective Dosage in Individual Patients?

Abstract

A double‐blind, randomized, cross‐over study of additional vigabatrin (γ‐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 patients with refractory epilepsy. Nineteen completed the trial satisfactorily. Fewer seizure days were reported during VGB treatment [placebo 41, VGB 23, p < 0.05, 95% confidence interval (CI) −1.5 to −14]. An overall reduction in median seizure numbers failed to reach statistical significance (n = 19; placebo 52, VGB 32, NS, 95% CI −18 to + 24). Subgroup analysis, however, showed a significant reduction in partial 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 22, NS, 95% CI − 18 to + 11). A deterioration in control of partial seizures 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 resistant patient developed a therapeutic response, and 2 other patients reported an additional useful reduction in seizures. In the remaining 8 patients, seizure frequency did not change. VGB did not appear to benefit tonic‐clonic seizures. Serum VGB concentrations were higher during 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 the trial. VGB is useful adjuvant therapy for treatment of partial seizures. There may be a ceiling to effective dosage. This demands individual dose titration for each patient.