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Neuropsychological and neurophysiologic effects of carbamazepine and levetiracetam

From the Departments of Neurology (K.J.M., D.W.L.) and Clinical and Health Psychology (D.W.L.), University of Florida, Gainesville; San Francisco Brain Research Institute and SAM Technology (A.G., L.K.M., M.E.S., M.E.S., B.M.E., C.B.), CA; Department of Neurology (P.G.R.), Medical College of Georgia, Augusta; and Department of Neurology (G.K.M.), Georgetown University, Washington, DC.

Address correspondence and reprint requests to Dr. Kimford J. Meador, Department of Neurology, University of Florida (PO Box 100236), McKnight Brain Institute (L3-100), 100 South Newell Drive, Gainesville, FL 32610 kimford.meador{at}neurology.ufl.edu

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.

Abbreviations: ABL = anticonvulsant blood level; AED = antiepileptic drug; ANOVA = analysis of variance; CBZ = carbamazepine; ERP = event-related potential; LDA = linear discriminant analysis; LEV = levetiracetam; POMS = Profile of Mood States; POz = parieto-occipital site; SAM = Sustained Attention and Memory; SEALS = Side Effects and Life Satisfaction Scale; QOLIE-89 = Quality of Life in Epilepsy-89; VSAT = Visual Serial Addition Test; WM = working memory.

Supplemental data at www.neurology.org

Supported by a grant from UCB Pharma to Dr. Meador. The cognitive neurophysiologic component of this study was supported by a grant from the NINDS to Dr. Gevins.

Disclosure: Drs. Loring and Motamedi have received honoraria from UCB Pharma.

Received July 10, 2006. Accepted in final form June 5, 2007.

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