title: Double-blind substitution of vigabatrin and valproate in carbamazepine-resistant partial epilepsy. 012 Study group.
abstract: 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 CBZ was withdrawn over a further 2 months in responders ( > or = 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 > or = 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.
authors: Department of Medicine and Therapeutics, Western Infirmary, Glasgow, Scotland, UK. martin.j.brodie@clinmed.gla.ac.uk
authors: M J
authors: MJ
authors: Brodie
authors: J P
authors: JP
authors: Mumford
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D002220:Carbamazepine / Q000627:therapeutic use*; D002648:Child; D004311:Double-Blind Method; D004351:Drug Resistance; D004828:Epilepsies, Partial / Q000188:drug therapy* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D019233:Retreatment; D016896:Treatment Outcome; D014635:Valproic Acid / Q000009:adverse effects / Q000627:therapeutic use*; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D002220:Carbamazepine; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; D020888:Vigabatrin