The cognitive and behavioral effects of carbamazepine (CBZ) and lamotrigine (LTG) were assessed and compared in 25 healthy adult volunteers, using a double-blind, randomized crossover design with two 10-week treatment periods, at the Medical College of Georgia, Augusta, and New York University, New York. A neuropsychological test battery was administered at the end of each AED treatment period (CBZ mean dose 696 mg/day, and LMG 150 mg/day), at pretreatment baselines, and at 1 month after completion of the last AED treatment. Comparison of the two AEDs showed better cognitive and subjective behavioral measures for LMG than CBZ. Measures included cognitive speed, memory, graphomotor coding, neurotoxic symptoms, mood, sedation, and perception of cognitive performance. Compared to nondrug periods, performance on CBZ was worse on 62% of the variables and better on 0%, while LMG was worse on 2.5% and better on 2.5% of variables. 
COMMENT. Lamotrigine in healthy adult volunteers has fewer adverse cognitive and behavioral effects than carbamazepine at midrange standard anticonvulsant doses. Cognitive and behavioral side effects of AEDs are significant factors in decision to treat and duration of therapy of seizure disorders, especially in children. Equally important is a neuropsychological impairment that may be associated with the epilepsy syndrome, independent of any effects of AEDs.