Effects of Chronic Gabapentin and Carbamazepine Treatment on EEG, Alertness, and Cognition in Healthy Volunteers
Abstract number :
2.240
Submission category :
Year :
2000
Submission ID :
3186
Source :
www.aesnet.org
Presentation date :
12/2/2000 12:00:00 AM
Published date :
Dec 1, 2000, 06:00 AM
Authors :
Martin C Salinsky, Lawrence M Binder, Barry S Oken, Daniel S Storzbach, Oregon Health Science Univ, Portland, OR; Portland VAMC, Portland, OR.
RATIONALE: Patients receiving antiepileptic drugs (AEDs) often complain of adverse effects on alertness and cognition. We studied the effects of two common AEDs on quantitative EEG, alertness, and cognitive/mood measures. METHODS: A 12 week, randomized, double-blind, parallel group study of gabapentin (GBP) and carbamazepine (CBZ) in healthy volunteers. Twenty-three subjects completed the protocol. All achieved the target dose of 3600mg GBP or 1200mg CBZ without clinical toxicity. At baseline and week 12 subjects underwent quantitative EEG, Awake Maintenance Task (AMT), and neuropsychological testing. Subjective measures included the Profile of Mood States and the Portland Neurotoxicity Scale (PDXnt). Test-retest changes were compared with those of 73 control subjects based on regression equations for each measure. Regression based Z-scores were calculated for each subject and measure. Between group comparisons used the Wilcoxon test or ANOVA. RESULTS: Both CBZ and GBP significantly decreased the peak frequency (PKF) of the alpha rhythm (by 1.0 and 0.3 Hz respectively), and increased theta and delta power. Differences between CBZ and GBP were significant (p=0.002). Eleven CBZ vs. five GBP subjects exceeded the 95% confidence interval for PKF. CBZ significantly increased AMT drowsiness as compared to controls. Subjective toxicity was demonstrated on all target measures, particularly PDXnt (p<0.001). Cognitive tests revealed subject vs. control group effects on two of eight target measures (Digit Symbol, Stroop). Differences between CBZ and GBP were not significant but favored GBP on 22 of 27 measures. EEG slowing (>2.4 SD) defined subjects with significant negative effects on four of eight target cognitive measures, and correlated with subjective cognitive toxicity. CONCLUSIONS: Chronic CBZ and GBP treatment induced slowing of EEG background rhythms. These effects correlated with cognitive complaints and were associated with negative cognitive effects. At these doses, CBZ induced greater EEG slowing than GBP and also affected ability to maintain wakefulness. EEG may be a useful marker for adverse CNS effects of AEDs.