Abstracts

RATIONALE: Efficacy of new AEDs is usually established in controlled studies carried out over a limited time-period. Unfortunately, long-term efficacy has to be assessed during open trials, which in-turn, places limitations on the validity of their data. When the outcome variable is the achievement of a long-lasting seizure-free state during an open trial, the validity of the data becomes more acceptable. The purpose of this study was to determine whether high dose lamotrigine monotherapy (LTGM) can yield a long lasting seizure-free state in pts. with intractable partial epilepsy. METHODS: We followed prospectively the seizure frequency of 100 consecutive patients, 60 women and 40 men, with a mean age of 35?13.8 years who were started on LTG with the intention of switching them to LTGM. All patients had failed to reach a seizure-free state on at least four AEDs at maximal doses. Patients recorded their seizures in a calendar, which was reviewed at each visit. The AED(s) present at the start of LTG were tapered off once a LTG serum concentration at steady state (Css) of 10 mg/l was reached. Thereafter, the dose of LTG was further increased until a seizure-free state was achieved or adverse events (AE) were reported. We measured LTG Css corresponding to the final dose, provided the prior AED had been discontinued for at least eight weeks. LTG Css were correlated with AE. The main outcome variable of the study was the number of patients that became seizure-free for a minimum of 12 months, (from the time they reached their final dose) and remained seizure-free until their last follow-up visit. Data were analyzed on an intent-to-treat basis. RESULTS: 81 patients (81%) achieved LTGM at a mean dose of 10.9?6.3 mg/kg that yielded a Css of 18.9?6.3 mg/l. 34 patients (34%) were seizure-free for at least six months and 22 (22%) for at least 12 months. 19 patients (19%) have remained seizure-free since they reached their final LTG dose for a median period of 35 months (mean: 34.6?16). 35 of the 81 patients (43%) reported AE during LTGM. There was no correlation between AE and LTG dose (p=0.2) or Css (p=0.7). CONCLUSIONS: High dose LTGM should be considered in patients with refractory partial epilepsy.