Prophylaxis with diphenylhydantoin and phenobarbital in alumina-gel monkey model. II. Fourth-month follow-up period: seizure, EEG, blood and behavioral data.

This study, a 4-month follow-up period of a 12-month treatment study by the present authors, was concerned with the permanent effects of treatment with diphenylhydantoin and phenobarbital in the alumina-gel monkey model. Whereas the 8 drug animals during withdrawal increased their seizure frequency, duration, and severity, those 4 animals having received 120 mg/kg/day DPH in weeks 6-12 had one-half the number of seizures of the 4 placebo monkeys in the follow-up period. The other 4 drug animals who had continued to receive 60 mg/kg/day DPH during those weeks had two to four times the number of seizures of the placebo group during posttreatment. (All drug monkeys received 80 mg/kg/day of DPH from weeks 13-52 and 6 mg/kg/day of phenobarbital throughout the 12-month treatment period). The results reaffirm the problems of drug withdrawal and the importance of altering seizure mechanisms with sufficiently high doses of efficacious anticonvulsants rather than merely treating epileptic manifestations at lower doses.