Vigabatrin reduces seizure activity primarily by increasing gamma aminobutyric acid (GABA) concentrations in the brain. Limited information is available concerning the role of this new drug as monotherapy for partial seizures.
All double-blind controlled studies of vigabatrin in the treatment of epilepsy have been placebo-controlled and have evaluated vigabatrin as an add-on drug in uncontrolled epilepsy. Only two studies of vigabatrin as monotherapy have been published. Chadwick and colleagues conducted a study of the safety and efficacy of vigabatrin compared with that of carbamazepine in the treatment of newly diagnosed partial seizures.
The double-blind randomized study began with 459 patients 12 to 65 years of age with previously untreated partial seizures. The study was completed by 130 patients assigned to receive vigabatrin and 132 patients assigned to receive carbamazepine. The study was conducted at 44 centers in 15 countries.
Vigabatrin was initiated in a daily dosage of 1 g, which was increased to an initial maintenance dosage of 2 g daily. Carbamazepine was initiated in a daily dosage of 200 mg, which was increased to an initial maintenance dosage of 600 mg daily. Dosages were adjusted upward or downward depending on the occurrence of seizures or adverse effects. Daily dosages ranged from 1 to 4 g of vigabatrin and 200 to 1,600 mg of carbamazepine to achieve seizure control with minimum toxicity. The primary outcome measure was the time to treatment failure because of adverse effects or lack of seizure control. Secondary outcomes included time to achieve remission lasting at least six months, time to the first seizure and the incidence and severity of adverse events.
In the intention-to-treat group, lack of therapeutic effect was the reason for withdrawal in 23 patients receiving vigabatrin and in nine patients receiving carbamazepine. Patients taking carbamazepine were more likely to withdraw before patients receiving vigabatrin, particularly during the first four to six months. After 12 months, remission for at least six months was achieved in 107 patients who received vigabatrin and in 116 patients who received carbamazepine.
The number of patients experiencing adverse events was similar in each group. At least one adverse event occurred in 195 (85 percent) of 229 patients who received carbamazepine and in 191 (84 percent) of 228 patients who received vigabatrin. Psychiatric symptoms were more common with vigabatrin (25 percent versus 15 percent), as was weight gain (11 percent versus 5 percent). Rash was reported by 22 (10 percent) patients taking carbamazepine, compared with seven (3 percent) patients taking vigabatrin. The most common reason for withdrawal from the medication was an adverse event, which was the reason for withdrawal in 43 patients who received vigabatrin and 61 patients who received carbamazepine.
The authors conclude that vigabatrin appears to be less effective but better tolerated than carbamazepine as monotherapy for newly diagnosed partial seizures. In view of the findings, plus new information that links long-term vigabatrin therapy to visual field loss, the authors do not recommend vigabatrin as first-line monotherapy.