Mj. Brodie et Jp. Mumford, Double-blind substitution of vigabatrin and valproate in carbamazepine-resistant partial epilepsy, EPILEPSY R, 34(2-3), 1999, pp. 199-205
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 retrospec
tive baseline on unchanged CBZ dosage, a month's prospective baseline, a sh
ort titration phase, and an assessment period lasting 3 months on duotherap
y. CBZ was withdrawn over a further 2 months in responders (greater than or
equal to 50% monthly seizure reduction compared with baseline), who contin
ued on alternative monotherapy for 3 or more months. If seizure control det
eriorated, 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 se
ven partial seizures per month fulfilled the criteria for the intention-to-
treat analysis. 53 and 51% of patients in the VGB and VPA group respectivel
y 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 durin
g the final 3 month treatment period. VGB and VPA, which increase neuronal
inhibition mediated by gamma aminobutyric acid, can be added to or substitu
ted for CBZ when this Na+ channel blocker fails to control partial seizures
. This lends credence to the hypothesis in support of a mechanistic approac
h to the management of epilepsy. (C) 1999 Elsevier Science B.V. All rights
reserved.