Abstracts

Little is known about seizure recurrence in newly emergent epilepsy if an antiepileptic drug (AED) is loaded vs. being titrated. Although many double-blind randomized studies have evaluated AEDs titrated to a target dose, titration-period seizure occurrence has not been reported. We report seizure occurrence during titration in a double-blind trial comparing topiramate (TPM 100 and 200 mg/day) with carbamazepine (CBZ, 600 mg/day) or valproate (VPA, 1250 mg/day) in newly diagnosed epilepsy. Patients [ge]6 yrs were eligible if epilepsy had been diagnosed [lt]3 mos before screening; no seizures or syndromes were excluded. Patients were untreated or treated [le]6 wks. Patients were randomized to TPM 100 or 200 mg/day or the investigator[rsquo]s choice of CBZ or VPA. Titration achieved target doses in 4 or 5 wks (see table). Dose reductions were not allowed. Time to 1st seizure provided means for post-hoc analysis of seizure occurrence during titration. The intent-to-treat population was 613 patients. Median time since epilepsy diagnosis, 1 mo; median time since first lifetime seizure, 5 mo. Study groups: CBZ, N=126 patients; VPA, N=78; TPM, 409. 68% of those randomized to TPM and CBZ and 59% randomized to VPA had 1-3 seizures in the 3-mo baseline. Table shows proportion of patients having their first seizure during titration (Kaplan-Meier analysis of time to 1^st seizure).[table1] Although the CBZ data seem to show an advantage of more aggressive AED initiation with substantially fewer patients having [ge]1 seizure within Week 1 (CBZ dose, 33% of target; VPA, 20%; TPM 100, 25%; TPM 200, 12.5%), any such advantage was short-lived; seizure recurrence was not significantly different among TPM, CBZ, or VPA-treated patients as dosages approached 100% of target and were maintained. This study, in which no seizure type or syndrome was excluded, shows that 70% of patients with newly diagnosed epilepsy can expect to have no seizures during titration. These data raise interesting questions about the risk-benefit of aggressively initiating AED therapy and provide information useful for counseling patients starting AED therapy. (Supported by Johnson [amp] Johnson Pharmaceutical Research [amp] Development)