Abstracts

The sodium channel blockers carbamazepine (CBZ) and phenytoin (PHT) are established antiepileptic drugs (AEDs). Although both are sodium channel blockers (SCB), different mechanisms on the sodium channel may result in improved seizure control when combined. Oxcarbazepine (OXC) is a SCB which may also improve seizure control when added to other SCBs or other AEDs with different modes of action. This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study designed to evaluate the efficacy and safety of OXC as adjunctive therapy in children aged 3 to 17 years with refractory partial seizures (with or without secondarily generalized seizures) (Glauser et al. Neurology 2000;54:2237-2244). This study consisted of a 56-day baseline phase and a 16-week double-blind treatment phase with 2 weeks[apos] titration and 14 weeks[apos] maintenance. Eligible patients had uncontrolled ([ge]8 seizures/month during baseline) partial seizures while receiving treatment with 1 or 2 AEDs. OXC was initiated at a dose of 10 mg/kg/day, titrated to a target dose of 30-46 mg/kg/day or optimum daily dose, and patients were maintained on their final fixed dose. Concomitant AEDs included: CBZ, valproate (VPA), lamotrigine (LTG), and PHT. The percentage of patients who experienced seizure reductions of [gt]50%, [gt]75%, and 100% seizure freedom was analyzed. We performed a subanalysis by concomitant AED. Adverse events were recorded. 267 patients were randomized and treated (OXC n=138, placebo n=129), 236 (88.4%) completed the double-blind treatment phase, and 18 (6.7%) discontinued due to adverse events . A [gt]50% reduction in mean seizure frequency was observed in 38.2% of OXC-treated patients who were receiving concomitant CBZ; similar results were observed for OXC-treated patients taking VPA, PHT, or LTG as part of their AED regimen. The response rates observed with each concomitant AED are shown below. The most common adverse events involved the CNS or gastrointestinal systems and occurred at similar frequency regardless of the concomitant AED. [table1] The efficacy of OXC as add-on therapy in children with refractory partial seizures is consistently observed whether added to CBZ, VPA, PHT, or LTG. This subanalysis demonstrates the benefit of adding OXC to the standard sodium-channel blockers CBZ or PHT in the treatment of patients with refractory seizures. (Supported by Novartis Pharmaceuticals)