Abstracts

Rationale: Stiripentol (STP) is an anticonvulsant agent which inhibits the activity of several cytochromes P450 resulting in increased plasma concentration of carbamazepine (CBZ). In an open study of STP with CBZ in partial epilepsy, 58% of children experienced an over 50% decrease in seizure frequency (Epilepsia 1999, 40, 1618-26). To confirm these results, patients with refractory partial epilepsy receiving CBZ (ages 2-17 years) were included in a randomised placebo-controlled add-on trial. As of 1 May 2000, 31 patients had concluded the study. Methods: Phase I of the trial was open: after 1 month single-blind placebo, STP was added at 50-mg/kg/day and CBZ decreased by half in 65 patients, and 1 month later STP could be increased to 75-mg/kg/day if seizures persisted. Within 3 months of STP treatment, 31 patients responded (over 50% reduction in seizure frequency during the 3rd month-STP compared to placebo period). The remaining 34 non-responding patients stopped STP. Responders were double-blindly randomized for a 2 months period (phase II), to either continue STP at the same dose (16 cases) or to receive placebo while doubling the dose of CBZ (15 cases). The switch from open to double-blind lasted 3 weeks during which CBZ was blindly increased to the maximum tolerated dose. Patients escaped from the study when the number of seizures reached that of the single-blind placebo period (phase I). Thus, the primary end point was the number of patients dropped-out during double-blind period. Results: Interim analyses show that 40% more patients dropped-out on placebo (6/10) than on STP (2/10). Conclusion: Preliminary results confirm that STP combined to CBZ is superior to CBZ in childhood partial epilepsy.