Neuropsychological and neurophysiologic effects of carbamazepine and levetiracetam

Background: The relative effects of levetiracetam (LEV) and carbamazepine (CBZ) on cognitive and neurophysiologic measures are uncertain. Methods: The effects of LEV and CBZ were compared in healthy adults using a randomized, double-blind, two-period crossover design. Outcome measures included 11 standard neuropsychological tests and the score from a cognitive- neurophysiologic test of attention and memory. Evaluations were conducted at screening, baseline pre-drug treatment, end of each maintenance phase (4 weeks), and end of each washout period after drug treatment. Results: A total of 28 adults (17 women) with mean age of 33 years (range 18 to 51) completed the study. Mean maintenance doses (+/- SD) were CBZ = 564 mg/day (110) and LEV = 2,000 mg/day (0). CBZ was adjusted to mid-range therapeutic level. Mean serum levels (+/- SD) were CBZ = 7.5 mcg/mL (1.5) and LEV = 32.2 mcg/mL (11.2). An overall composite score including all measures revealed worse effects for CBZ compared to LEV (p <= 0.001) in the primary analysis and for CBZ p <= 0.001) and LEV (p <= 0.05) compared to non-drug in secondary analyses. Across the 34 individual variables, CBZ was worse than LEV on 44% (15/34); none favored CBZ. Compared to the non- drug average, CBZ was worse for 76% (26/34), and LEV was worse for 12% (4 of 34). Sensitivity and specificity of standard neuropsychological tests and the cognitive-neurophysiologic test were determined to direct future studies; detection was most accurate by the cognitive-neurophysiologic test. Conclusions: Levetiracetam produces fewer untoward neuropsychological and neurophysiologic effects than carbamazepine in monotherapy at the dosages and timeframes employed in this study.