Abstracts

Oxcarbazepine (OXC), carbamazepine (CBZ) and phenytoin (PHT) are first-line antiepileptic drugs (AEDs) as monotherapy and are widely used in the treatment of epilepsy. Although all are sodium channel blockers, different mechanisms on the sodium channel may result in improved seizure control when they are combined or added to AEDs with different mechanisms of action. This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study designed to evaluate the efficacy and safety of OXC 600, 1200 and 2400 mg/day as adjunctive therapy for 28 weeks in patients with refractory partial seizures (Barcs et al. Epilepsia 2000;41:1597-1607). This study consisted of an 8-week baseline, 2-week titration, 24-week maintenance, and a 2-week down titration. Eligible patients were 15-65 years old with simple or complex partial seizures (with or without secondarily generalized seizures) who were currently receiving treatment with 1-3 AEDs and were poorly controlled ([ge]4 seizures/month during baseline). OXC was initiated at 300 mg/day, increased to 600 mg on day 2, titrated up 300 mg every 2 days over 2 weeks, and maintained on patients[apos] final fixed dose. Efficacy assessments included: percentage of patients who experienced seizure reductions of [gt]50%, [gt]75% and 100%. We performed a subanalysis of these data for the 4 most common concomitant AEDs: CBZ, valproate (VPA), PHT and lamotrigine (LTG). Adverse events were recorded. A total of 692 (n=519 OXC, n=173 placebo) were randomized and received treatment. Of the OXC-treated patients, 52.6% completed the double-blind treatment phase and 38.5% discontinued due to adverse events. A [gt]50% reduction in mean seizure frequency was observed in 33% to 40.5% of patients and 100% reduction was observed in 11.9% to 14.5% of patients whether CBZ, VPA, PHT or LTG were part of their AED regimen. The response rates as observed by concomitant AED for all OXC-treated patients are shown below. A similar response was observed when patients[rsquo] data were analyzed by OXC dose level, with a trend showing improved seizure reduction with increased OXC dose. The most common adverse events involved the CNS or gastrointestinal systems and occurred at similar frequency regardless of concomitant AED.[table1] In this subanalysis, OXC was shown to reduce seizure frequency whether added to CBZ, PHT or other AEDs in patients with refractory seizures. Improved seizure control when OXC is added to the standard sodium channel blockers CBZ or PHT suggests that its mode of action may involve distinct mechanisms. (Supported by Novartis Pharmaceuticals)