Abstracts

Lamotrigine (LTG) was shown in a double-blind, randomized trial to be an effective treatment for children newly diagnosed with typical absence seizures (TAS; Epilepsia, 40(7):973-979, 1999). Since an escalation period is required to reach an effective mean maintenance dose, a post-hoc analysis was conducted to determine the onset of efficacy during the LTG dose escalation phase. Patients were 2-16 years, with newly diagnosed TAS by clinical/EEG features on 1 of 2 3-min hyperventilation (HV) tests. The trial included a screen, an open-label escalation phase (OLEP, 4-18 weeks) with LTG (LAMICTAL[reg]), a double-blind treatment phase (DBTP, [le] 4 weeks), a treatment transition phase (1 week), and an exit visit. Patients who became seizure-free (SF) during the OLEP entered the DBTP and were randomized (1:1) to taper off the LTG and receive placebo, or to continue taking LTG at the effective dose achieved during the OLEP. The primary endpoint was the percent of patients who remained SF on HV-EEG during the DBTP. Demographics: Intent-to-Treat population n=45, efficacy population n=42, male=36%, mean age (SD)=7.4 kg (2.6). Seventy-one (71%, 30/42) of patients became SF during the OLEP with LTG. The median LTG dose providing complete SF was 5 mg/kg/day. The earliest onset of complete control of TAS occurred at a LTG dose of 2 mg/kg/day in 2 of 30 (6.7%) of patients who became SF and in 2 of 42 (4.8%) of all patients treated. The percent of patients becoming SF increases with further LTG dose increases, reaching 12 of 30 (40%) patients and 18 of 30 (60%) patients who became SF at LTG doses of 4 and 5 mg/kg/day, respectively. In the 30 patients who became SF, 17% sustained at least 25% reduction in clinical manifestations (e.g., blinking, staring) at a LTG dose of 0.5 mg/kg/day and 30% sustained at least 25% reduction at a LTG dose of 1 mg/Kg/day. [italic]Note: LTG dosing schedule in this trial exceeds the current dosing schedule recommended in the product label.[/italic] This study shows that LTG monotherapy is effective for the control of TAS in children with the initial onset of complete control at a LTG dose of 2mg/kg/day. (Supported by GlaxoSmithKline.)