EFFECTS OF PHENYTOIN ON COGNITIVE-MOTOR PERFORMANCE IN CHILDREN AS A FUNCTION OF DRUG CONCENTRATION, SEIZURE TYPE, AND TIME OF MEDICATION

Fifty children with well-controlled seizures who were receiving phenytoin (PHT) monotherapy were tested three times at weekly intervals on a cognitive-motor test battery. The first assessment served as a practice session, and PHT was given either before or withheld until after testing to create peak and trough concentrations, respectively, in the second and third sessions. On average, PHT levels as measured in saliva were in the low therapeutic range. The experimental condition (PHT before or after test sessions) was randomized and balanced across subjects, and assessments were made with examiners blind to diagnosis and timing of PHT ingestion. A variety of statistical models was used to analyze for the effect of age, diagnosis (partial vs. generalized epilepsy), PHT order, PHT concentration (as measured in saliva), and trough/peak concentration effects. Greater age was consistently associated with better performance, but diagnosis, PHT concentration levels, and transition from trough to peak concentration days had few discernible effects on psychomotor performance. Thus, fluctuations in PHT, of the order of 50%, appear to have no or immeasurably small effects in children with well-controlled seizures receiving monotherapy in low therapeutic dosages.