Oxcarbazepine as add-on therapy in Thai epileptic patients with refractory partial seizures

Abstract

The purposes of the present study were to evaluate the efficacy and safety of oxcarbazepine(OXC) in the dosage of 600 and 1200 mg/d as add-on therapy in Thai epileptic patients with uncontrolled partial seizures and to explore therapeutically relevant plasma concentration of 10-monohydroxy derivative; MHD which responsible for the pharmacologic effect of OXC. A total of 39 patients aged 15-65 years with uncontrolled partial seizures with or without secondarily generalized seizures were evaluated in a randomized, double-blind trial consisting of three phases: 1) a 56-day baseline phase (patients maintained on their current anti-epileptic drugs); 2) a 98-day double-blind treatment phase (OXC either 600 or 1200mg/d orally was added); 3) an open-label extension phase. Data are reported only from the double-blind period; the open-label extension phase is ongoing. The primary efficacy variable was percentage change in seizure frequency per 28 days relativeto baseline and the secondary efficacy was treatment responder. The results showed that the median reduction in seizure frequency were 47% and 58% for patients receiving 600,1200 mg/d respectively. Of patients in the 600 and 1200 mg/d OXC group, 44% and 53% respectively, had more than 50% reduction in seizure frequency. No significant differences were found between two treatment groups (p>0.05) in both efficacy variables. Mean trough plasma concentrations of MHD were correlated with OXC dosage (p=0.000). During double-blind treatment phase, 85%and 84% of patients receiving 600 and 1200mg/d OXC, respectively, reported one or more adverse events (AEs) with mild to moderate degree, transient in nature. The most common AEs were related to the central nervous systems. In conclusion, OXC both dosage of 600 and 1200 mg/d as add-on therapy is effective and safe in Thai epileptic patients with uncontrolled partial seizures. The effectiveness of OXC seemed to be increased with increasing dosage.