Vigabatrin in the Treatment of Epilepsy: A Double‐Blind, Placebo‐Controlled Study

Abstract

The efficacy and tolerability of vigabatrin (gamma-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 less than or equal to 65 kg and 1.5 g twice daily for patients weighing greater than 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 greater than 50% reduction in seizure frequency and 4 of the 12 showed a greater than 75% reduction. Both the total number of seizures and the number of partial seizures were significantly reduced by vigabatrin (p less than 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 receiving 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Vigabatrin induced Cell loss in the Cerebellar Cortex of Albino Rats

“…Excessive glutamate binding to NMDA receptors allows entry of Ca 2+ into the post-synaptic neuron, causing necrotic cell death or apoptosis, whereas the excessive glutamate binding to non-NMDA receptors allows entry of Na + into the post-synaptic neuron, resulting in cytotoxic edema. Because glial cells also have these receptors, excessive glutamate leads to glial cell damage as well [20]. This could have been the underlying mechanism behind the cell loss in the present study too.…”

The effect of different vigabatrin treatment regimens on CSF biochemistry and seizure control in epileptic patients.

“…Vigabatrin (-y-vinyl GABA), a specific, enzymeactivated irreversible inhibitor of GABA-transaminase (GABA-T) has been shown to be an effective anti-convulsant agent for complex partial seizures (Gram et al, 1983;Browne et al, 1983;Rimmer & Richens, 1984;Gram et al, 1985;Loiseau et al, 1986;Schechter, 1986;Tartara et al, 1986;Tassinari et al, 1987). In all published studies to date vigabatrin has been administered orally on a twice-daily schedule.…”

Chronic Toxicity Studies with Vigabatrin, A GABA-Transaminase Inhibitor

“…Animal studies have shown that elevation of brain GABA by this mechanism can prevent experimental seizures (2 1- 23,29), and clinical trials have shown vigabatrin to have beneficial eKects in 'certain types of drug re-sistant or uncontrolled epilepsy (4,8,20,26,31,32).…”