• The long-term clinical, neurophysiologic, and psychological effects of add-on vigabatrin treatment were evaluated in a group of 36 mentally handicapped patients with drug-refractory epilepsy. After an initial 3-month follow-up period, 15 (42%) of 36 patients had at least a 50% decrease in seizure frequency compared with baseline. After a 2-year follow-up period, nine (25%) of 36 patients retained the initially observed antiepileptic effects of vigabatrin, and after 5 years, eight (22%) of 36 patients did so. Five (33%) of the 15 patients who initially exhibited a favorable antiepileptic response to vigabatrin lost that response during a 5-year follow-up. Partial-onset seizures represented the seizure type best controlled by vigabatrin. Side effects were mostly mild, and plasma levels of other antiepileptic medication remained unchanged. No impairment of psychological performance was observed during vigabatrin treatment compared with baseline. Also, no clear change was observed in the background or epileptiform activity in the electroencephalogram during the study. Our findings suggest that vigabatrin as an add-on therapeutic effectively controls seizures in a subpopulation of patients with severe epilepsy. In addition, the antiepileptic response, if achieved, is long lasting in about half of the patients.