Long-term open multicentre, add-on trial of vigabatrin in adult resistant partial epilepsy

Vigabatrin (VGB) has been shown in a number of clinical trials with varying designs to be effective and well-tolerated as both add-on therapy and mono therapy in epilepsy with partial seizures with or without secondary general ization as well as in infantile spasms. The present study is an open, long- term (1 year) extension of a randomized double-blind placebo-controlled mul ticentre Canadian trial of VGB in resistant partial adult epilepsy. The pre sent study was designed to examine the safety and long-term efficacy of VGB . Completers of the preceding double-blind study had their dose of VGB titrat ed to 4 g/day over 3 weeks. Patients were evaluated every 2-4 weeks and at week 14 were allowed to continue only if they achieved a 50% seizure reduct ion compared with pre-VGB baseline. In addition to neurological and physica l examinations, safety was assessed by a cognitive psychosocial test batter y, visual and somatosensory evoked potentials and MRI scans. Ninety-seven of 100 eligible patients entered the study, 53 of whom complet ed the 52 weeks. Fifty-eight percent of the patients had a greater than 50% seizure reduction in seizures vs, pre-VGB baseline. Seizure reductions of 56% and 45%, respectively, were seen in the VGB and placebo groups from the preceding study. Fifty-four percent of patients were judged by the investi gators to have experienced at least a moderate therapeutic effect. Disconti nuations were 29% for lack of efficacy and 12% for adverse effects. There w as a mean weight gain of 3.7 +/- 0.2 kg by end of study. Neurological/psych iatric side effects were the most common reason for withdrawal including th ree behavioral reactions attributed to the drug Which required temporary ho spitalization. There were no abnormalities on laboratory or special tests a nd there was a tendency for improvement on most tests of cognitive function and mood. Vigabatrin, as an add-on agent, is well-tolerated and can be of long-term b enefit in a substantial proportion of patients with intractable partial epi lepsy. (C) 2000 BEA Trading Ltd.