Members of the Departments of Pediatrics, Neurology, and Clinical Pharmacology and Toxicology at the Children’s Hospital and Ohio State University, Columbus, OH 43205, assessed neuropsychological function before and after carbamazepine monotheraphy at low ( <-7.5,ug/ml) and moderate (>8.0,ug/ml) plasma levels in 11 children (4 boys 7 girls, mean age 9.8 yrs) with controlled complex partial epilepsy. Carbamazepine caused significant impairments (P<.03) of efficiency in learning of new information (Paired Associates Test) and short-term memory scanning (Sternberg Memory and Reaction Time Paradigm) that were associated with moderate plasma concentrations within the therapeutic range. The decline in performance was not accompanied by a greater abnormality on the EEG or carbamazepine-induced seizure exacerbation (see Pediatric Neurology Briefs, Vol 1, No 1). A mild beneficial effect on speeded eye-hand coordination was suggested at moderate plasma levels but only in the nonpreferred hand. Except for a trend toward more rapid memory scanning, there was no change in performance from the baseline to low drug level assessment. 
COMMENT: These results are in agreement with previous studies in adults that have shown impairments in concentration and memory-processing with higher but therapeutic serum concentrations of carbamazepine . It has been suggested that the so-called “psychotropic“ effect of carbamazepine reported in cross over antiepileptic drug studies may have been related to the discontinuance of previous drugs rather than a positive carbamazepine effect and that cross over studies are potentially open to error by practice effects . The present study confirms the importance of comprehensive neuropsychological assessments to evaluate possible adverse cognitive side effects of antiepileptic drugs in children particularly at higher dose levels. The theoretical advantages of monotheraphy, notwithstanding, the tendency to rigid persistence of large and potentially toxic doses and delay in change to alternative therapy may result in subtle deficits in learning that might be avoided by selective combination therapies at lower dose levels.