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 phenyt oin (PHT) monotherapy were tested three times at weekly intervals on a cognitive-motor test battery. The first assessment served as a practi ce session, and PHT was given either before or withheld until after te sting to create peak and trough concentrations, respectively, in the s econd and third sessions. On average, PHT levels as measured in saliva were in the low therapeutic range. The experimental condition (PHT be fore or after test sessions) was randomized and balanced across subjec ts, and assessments were made with examiners blind to diagnosis and ti ming of PHT ingestion. A variety of statistical models was used to ana lyze for the effect of age, diagnosis (partial vs. generalized epileps y), PHT order, PHT concentration (as measured in saliva), and trough/p eak concentration effects. Greater age was consistently associated wit h better performance, but diagnosis, PHT concentration levels, and tra nsition from trough to peak concentration days had few discernible eff ects on psychomotor performance. Thus, fluctuations in PHT, of the ord er of 50%, appear to have no or immeasurably small effects in children with well-controlled seizures receiving monotherapy in low therapeuti c dosages.