Double-blind substitution of vigabatrin and valproate in carbamazepine-resistant partial epilepsy

Patients from 12 countries reporting two or more partial seizures per month despite treatment with optimal doses of CBZ were randomised to additional vigabatrin (VGB, 2-4 g daily) or sodium valproate (VPA, 1-2 g daily) using a double-blind, double-dummy design. The study included a 6 month retrospective baseline on unchanged CBZ dosage, a month's prospective baseline, a short titration phase, and an assessment period lasting 3 months on duotherapy. CBZ was withdrawn over a further 2 months in responders (greater than or equal to 50% monthly seizure reduction compared with baseline), who continued on alternative monotherapy for 3 or more months. If seizure control deteriorated, CBZ was reinstated and these patients were also followed up for 3 months. A total of 215 patients (108 VGB, 107 VPA) reporting a mean of seven partial seizures per month fulfilled the criteria for the intention-to-treat analysis. 53 and 51% of patients in the VGB and VPA group respectively achieved a monthly reduction in seizure numbers greater than or equal to 50%, respectively. 27 and 31% maintained alternative monotherapy. Overall, 17% (7% monotherapy, 10% duotherapy) of the VGB treated patients and 19% (8% monotherapy, 11% duotherapy) of the VPA group remained seizure-free during the final 3 month treatment period. VGB and VPA, which increase neuronal inhibition mediated by gamma aminobutyric acid, can be added to or substituted for CBZ when this Na+ channel blocker fails to control partial seizures. This lends credence to the hypothesis in support of a mechanistic approach to the management of epilepsy. (C) 1999 Elsevier Science B.V. All rights reserved.