Abstracts

Patients receiving antiepileptic drug (AED) therapy often complain of adverse effects on cognitive abilities. We compared the effects of AED monotherapy with oxcarbazepine (OXC) and phenytoin (PHT) on subjective complaints, cognitive measures, and EEG as a physiologic measure of brain function.
Healthy volunteers were randomized to receive OXC (up to 1200 mg/day) or PHT (up to 360 mg/day) in a double-blind trial. Doses were gradually escalated to tolerance over 8 weeks with an additional 4 week maintenance period. All subjects underwent cognitive testing and EEG recording for quantitative analysis (occipital peak frequency, median frequency, relative theta power) prior to AED initiation, and again after 12 weeks of treatment. Subjective measures included the Profile of Mood States (POMS) and the Portland Neurotoxicity Scale (PDXnt). Test-retest changes for all measures were scored against test-retest regressions obtained from 72 untreated controls. Between group comparisons were made using Wilcoxon tests.
Of 32 volunteers, 26 (14 OXC, 12 PHT) completed the study without protocol violations. Median blood levels ([mu]g/ml) were 19.6 for OXC (MHD) and 10.1 for PHT. There was significant test-retest slowing of the occipital EEG background rhythms (all measures p[lt]0.001) for both OXC and PHT groups as compared to the control group. There were no significant differences between the OXC and PHT groups. Negative test-retest changes on the POMS were of greater magnitude amongst PHT subjects with 4 of 6 scales showing significant change (as compared to controls) vs. 1 scale for the OXC group. Differences between the OXC and PHT groups were significant only for the Vigor scale (p[lt]0.05). Significant complaints on the PDXnt were noted for both the OXC (p[lt]0.01) and PHT (p[lt]0.001) groups vs. controls. Small ([lt]1 SD median change) but significant negative test-retest changes were seen for several cognitive measures (reaction time, tapping speed, Stroop, selective reminding, story recall) in one or both AED groups vs. controls. There were no significant differences between AED groups.
Fifty-five percent of subjects exceeded the 95% confidence interval (CI) for individual test-retest change on the EEG peak frequency measure. A maximum of 12% of subjects exceeded the 95% CI on any cognitive measure.
At conventional doses and titrations both OXC and PHT resulted in neurotoxicity complaints, which were somewhat greater for PHT. Cognitive tests revealed relatively mild negative effects which overall did not differentiate between these two AEDs. The relatively small number of subjects and considerable interindividual variability may have decreased the liklihood of finding significant differences between groups.
Quantitative measures of EEG background rhythms were considerably more sensitive to AED effects than were cognitive measures, and may be a useful measure of the CNS effect of AEDs.
[Supported by: Novartis Inc.]