a) Time to withdrawal for lack of efficacy or adverse events did not differ in newly diagnosed epileptic patients who received carbamazepine (n=226) or vigabatrin (n=220) in a double-blind, randomized, monotherapy study (p=0.318)
[109]. However, patients treated with carbamazepine were more likely to withdraw sooner than vigabatrin patients, especially in the first 4 to 6 months of therapy. The total daily dose of vigabatrin was 1 gram (g) during the first 6 weeks after randomization. Vigabatrin dose was increased to 2 g as an initial maintenance dose with a dose range from 1.5 g to 4 g daily. The initial daily dose of carbamazepine was 200 milligrams (mg) followed by an increase to 600 mg after 6 weeks. Maintenance doses of carbamazepine ranged from 400 mg to 1600 mg per day. No treatment differences between treatment groups were observed throughout the study. After 12 months of double-blind therapy, 107 vigabatrin and 116 carbamazepine patients had achieved 6 months of remission. The time to first seizure was significantly less for vigabatrin patients compared to carbamazepine patients (p=0.0003). Twenty-three vigabatrin and 9 carbamazepine patients withdrew from the study solely due to lack of therapeutic effect (p=0.0298). Drowsiness, fatigue, and headache were reported by more than 20% of patients with no differences between the two treatment groups observed.. Adverse events in the psychiatric system were reported significantly more often in vigabatrin patients (25%) compared to carbamazepine patients (15%; p less than 0.05). Likewise, more patients treated with vigabatrin experienced weight gain (11%) compared to those treated with carbamazepine (5%; p less than 0.05). Carbamazepine patients experienced significantly more adverse events in the skin and appendages system (23%) compared to vigabatrin patients (14%; p less than 0.05). A decrease in white-cell counts, uric acid and bilirubin and an increase in alkaline phosphatase were observed in carbamazepine patients.
b) Preliminary results from an open-label comparative trial (n=34) suggested the potential superiority of carbamazepine monotherapy over vigabatrin monotherapy in patients with newly diagnosed epilepsy
[110]. In this study, 5 patients treated with vigabatrin 50 milligrams/kilogram/day were considered non- responders; 1 of these patients subsequently failed to respond to carbamazepine. None of the patients treated with carbamazepine (plasma levels of 35 micromol/L) were considered non-responders. However, 3 carbamazepine-treated patients discontinued therapy due to hypersensitivity reactions.
c) Carbamazepine monotherapy was compared to vigabatrin monotherapy in patients with newly-diagnosed partial and/or generalized tonic-clonic seizures
[111]. Sixty percent of patients (n=50) were considered successfully treated in both groups; however, significantly more patients were totally seizure free while receiving carbamazepine. Vigabatrin therapy resulted in fewer side effects that resulted in discontinuation of therapy. Vigabatrin monotherapy may be an alternative to carbamazepine or other standard antiepileptic drugs in cases where patients are intolerant of toxic or cognitive side effects.