Progabide treatment in severe epilepsy: a double-blind cross-over trial versus placebo

Twenty therapy-resistant epileptic patients entered a double-blind, randomized, two-period, cross-over trial comparing progabide (19.3-36 mg/kg/day) and placebo as add-on drugs to standard therapy. Each period lasted 6 weeks with a gradual crossover during 4 days. Five patients were dropped because of reasons unrelated to treatment. Among the 15 patients who completed the study, seven had partial, six primary generalized, and two secondary generalized epilepsies. Preexisting antiepileptic drugs (AEDs) ranging from one to three per patient (mean 2.2 AEDs/patient) were maintained unchanged during the trial. Efficacy was assessed biweekly by means of total seizure counts, counts of each seizure type, and global clinical judgment. At the same time intervals, safety was assessed by means of reports of adverse events, clinical and neurological examination, laboratory tests, and measurement of plasma concentrations of progabide and associated AEDs. According to the clinical global judgment, eight patients were considered improved during progabide treatment. Seizures were reduced in 14 of 15 patients during the progabide as compared with the placebo period. During the progabide period, the reduction of the total seizure count was 45 and 58% in two patients and 88-97% in six patients. A significant reduction of the total seizure number was observed in the progabide period as compared with the placebo period, both in the whole patient group (p less than 0.01) and in the two subgroups of patients with generalized (p less than 0.01) and partial (p less than 0.05) epilepsies.(ABSTRACT TRUNCATED AT 250 WORDS)