Purpose: Antiepileptic drug (AED) therapy can be associated with neurotoxic side effects including cognitive dysfunction. Objective methods for detection of neurotoxicity in individual patients would be useful. We studied the effects of gabapentin (GBP) and carbamazepine (CBZ) on neurophysiologic and cognitive/behavioral measures in healthy volunteers.
Methods: In a 12-week, randomized, double-blind, parallel-group study of CBZ and GBP in healthy volunteers, 23 subjects completed the protocol. All achieved the target dose of 1,200 mg CBZ or 3,600 mg GBP. A structured EEG for quantitative analysis and a cognitive test battery were administered before AED therapy and again after 12 weeks of therapy. Test-retest differences were compared with those of 72 untreated control subjects.
Results: Both CBZ and GBP significantly decreased the peak frequency of the posterior (alpha) rhythm, with CBZ exerting a greater effect. Ten CBZ and six GBP subjects exceeded the 95% confidence interval (CI) for an individual. Cognitive tests revealed AED vs. control group effects for two of seven measures (Digit Symbol, Stroop) and all subjective measures. However, few subjects exceeded the 95% CI for any objective test. Differences between CBZ and GBP were not significant. Greater EEG slowing was associated with greater subjective neurotoxicity and poorer test-retest performance on a cognitive test summary measure.
Conclusions: Prolonged CBZ and GBP therapy induced EEG slowing that correlated with cognitive complaints and often exceeded the confidence interval for individual subjects. Quantitative EEG measures may be useful in the objective determination of AED-related neurotoxicity.