Single-blind, placebo-controlled dose-modification study of vigabatrin in refractory epileptic patients

Thirty patients with drug-resistant epileptic seizures received vigabatrin as add-on treatment in a single-blind, placebo-controlled dose-modification study. After a 3-month baseline period (1 month run-in, 2 months placebo), the patients were given vigabatrin (2 g/day, fixed dose) for 2 months, followed by a 2- to 6-month dose-titration period to achieve the individual optimal dose. Mean monthly seizure frequency significantly decreased from 29.5 seizures during the placebo period to 12.2 while taking vigabatrin, 2 g daily fixed-dose, and to 8.7 during titration phase with vigabatrin, 3 g daily, on average. Sixteen (53%) patients experienced a 50% or greater reduction in seizure frequency compared with placebo, and 3 (10%) patients reported a relevant improvement in seizure severity and duration while on vigabatrin, 3 g daily; therefore, 19 (63%) patients were allowed to continue the treatment on a long-term basis. Adverse effects, mostly drowsiness and weight gain, occurred particularly at the highest vigabatrin dose, although also in any case of mild severity. Serum phenytoin and phenobarbital levels significantly decreased during vigabatrin treatment. These results suggest that vigabatrin in a dose of 2-3 g daily is an effective and safe antiepileptic drug.