A comprehensive neuropsychological assessment of young adults (mean age 32) before and after treatment with phenytoin (PHT) for a 5 year study period is reported from the Regional Epilepsy Center, University of Washington School of Medicine, Seattle, Washington. In 3 groups of 11 patients each, the following medications were not changed and the median number of seizures per subject was 2: (a) PHT monotherapy; (b) PHT and other drugs; (c) drug regimens excluding PHT. Of 20 neuropsychological variables, none showed losses and 3 showed statistically significant improvements (Trail Making Part B, WAIS Performance IQ, WAIS Full-Scale IQ). The mental abilities of the groups were similar to each other at both the beginning and the end of the study. With normal therapeutic serum levels and well controlled seizures there was no evidence for any cognitive losses in patients treated with phenytoin over extended periods. [1]

COMMENT. Chronic use of phenytoin did not result in cognitive deterioration in young adults with well controlled seizures with onset after 16 years of age. Previous reports suggesting PHT-related cognitive deterioration were complicated by poor seizure control and were limited by less sophisticated tests than those used in the above study. Mikati M et al. at the Department of Neurology, Children’s Hospital, Harvard Medical School, have found significant differences in potency and plasma concentrations of brand name PHT and generic PHT monotherapy [2]. Variability in capsule content may be an important factor to be considered in trials of medications such as PHT that manifest nonlinear pharmacokinetics.