A double-blind, placebo-controlled study of Vigabatrin three g/day in patients with uncontrolled complex partial seizures

Abstract

This study compared the efficacy and tolerability of vigabatrin 3/day as add-on therapy with that of placebo in patients with focal epilepsy whose complex partial seizures were difficult to control with established antiepilepsy drug therapy. We enrolled 203 patients; 182 (90 placebo; 92 vigabatrin) received drug therapy under double-blind conditions. We increased the daily dosage to 2.5 g/day during a 4-week titration segment and maintained it at 3 g/day during the 12-week maintenance segment. By analyses we found a statistically significant lower frequency of seizures (complex seizures plus partial seizures secondarily generalized) at the end of the study for patients receiving vigabatrin than for those receiving placebo. The median monthly frequency was reduced by three seizures per 28 days in the placebo group (baseline, 8.3; end of study, 7.5) (p = 0.0002). Therapeutic success (a 50% reduction from baseline in mean monthly seizure frequency) was attained in 40 of the vigabatrin patients (43%) compared with 17 of those treated with placebo (19%) (p < 0.001). Vigabatrin significantly increased the mean number of seizure-free days per 28 days (2.2 days) compared with placebo (0.5 days) (p = 0.0024). Mean trough serum vigabatrin concentration during therapy was 8.6 +/- 7.7 micrograms/ml. The oral clearance of vigabatrin was determined to be 7.8 L/hr, and the elimination half-life was 8.4 hours. No clinically important changes in MRI, evoked potential, or other laboratory tests were noted during vigabatrin treatment. The results of this study indicate that 3 g/day vigabatrin is more effective than placebo as add-on therapy. Vigabatrin was well tolerated, compliance was high with twice-daily administration, and therapy did not result in clinically relevant drug interactions.

Vigabatrin-induced peripheral visual field defects in patients with refractory partial epilepsy

“…The present analysis verifies that visual field constriction, when it occurs, is most often mild or moderate and is not associated with symptoms INTRODUCTION Vigabatrin (Sabril  ), a selective and irreversible γ-aminobutyric acid transaminase inhibitor (Ben-Menachem, 1995), is effective as adjunctive therapy for adult patients with refractory complex partial seizures , French et al, 1996, Sander et al, 1990 and as monotherapy for infants with infantile spasms (West syndrome) (Aicardi et al, 1996, Appleton et al, 1999, Chiron et al, 1990, Chiron et al, 1997, Elterman et al, 2001, Wohlrab et al, 1998. Vigabatrin has been approved for these indications in the United…”

The Potential for Vigabatrin‐Induced Intramyelinic Edema in Humans

“…Published studies of MRI studies in epilepsy patients treated wtih VGB have reported no abnormalities suggestive of IME (27,(65)(66)(67)(68)(69). The types of MRI changes associated with IME in rats and dogs, such as abnormal foci of increased signal intensity on long TR images, increased T,-relaxation time, correlation between T,-relaxation time and duration of VGB treatment, or foci of decreased signal on T,-weighted images, have not been observed in humans.…”

Fragile X Syndrome: The GABAergic System and Circuit Dysfunction

“…Two clinically available, FDA-approved anticonvulsants function like nipecotic acid to increase the avail- French et al, 1996;Chiron et al, 1997 ability of GABA and therefore could show efficacy in FXS. The first, tiagabine, specifically blocks the presynaptic GABA transporter 1 (GAT1), thus increasing synaptic GABA levels and enhancing phasic and tonic GABAergic inhibition [Nielsen et al, 1991].…”