Vigabatrin in the treatment of epilepsy: A double-blind, placebo-controlled study

The efficacy and tolerability of vigabatrin (γ-vinyl GABA, GVG) given as add-on therapy to 23 adult outpatients with severe drug-resistant epilepsy (17 with partial seizures), were studied using a double-blind, placebo-controlled, crossover design. The study consisted of two 7-week periods during which vigabatrin and placebo were administered in random sequence. Dosage was 1.0 g twice daily for patients weighing ≤65 kg and 1.5 g twice daily for patients weighing >65 kg. Three patients were dropped from the study, two for reasons unrelated to treatment and one because of the appearance of vertigo, headache, dysarthria, and ataxia, which subsided rapidly when vigabatrin was stopped (3 g daily). Sixteen of the 20 patients available for analysis showed a decrease in the total number of seizures as compared with the placebo period. Of these, 12 showed a >50% reduction in seizure frequency and 4 of the 12 showed a >75% reduction. Both the total number of seizures and the number of partial seizures were significantly reduced by vigabatrin (p <0.01). Only in the patient who dropped out were severe adverse effects seen. The most frequently reported unwanted effect was mild drowsiness, which developed in seven patients on vigabatrin and in one on placebo. Positive effects, however, were also seen with six patients who reported an improved sense of well-being while receiveing vigabatrin as compared with only 1 during the placebo period. No consistent changes in electrocardiogram (ECG), electroencephalogram (EEG), and visual-, auditory-, and somatosensory-evoked potentials were seen during the study. Serum levels of associated anticonvulsants remained unchanged, with the exception of a decrease in serum phenytoin during vigabatrin in the only phenytoin-treated patient. We conclude that add-on treatment with vigabatrin is effective and well tolerated in adult patients with drug-resistant epilepsy.