Differential cognitive and behavioral effects of carbamazepine and lamotrigine

Background: The relative cognitive and behavioral effects of lamotrigine compared with the older standard antiepileptic drugs (AED) are uncertain. Objective: To directly compare the cognitive and behavioral effects of carbamazepine and lamotrigine. Methods: The cognitive and behavioral effects of carbamazepine and lamotrigine were assessed in 25 healthy adults using a double-blind, randomized crossover design with two 10-week treatment periods. During each treatment condition, subjects received either lamotrigine (150 mg/day) or carbamazepine (mean 696 mg/day) adjusted to a dose to achieve midrange standard therapeutic blood levels (mean 7.6 mug/mL). Subjects were tested at the end of each AED treatment period and in three drug-free conditions (two pretreatment baselines and a final posttreatment period [1 month after last AED]). The neuropsychological test battery included 19 measures yielding 40 total variables. Results: Direct comparison of the two AED revealed significantly better performance on 19 (48%) variables for lamotrigine but none for carbamazepine. Differences spanned both objective cognitive and subjective behavioral measures, including cognitive speed, memory, graphomotor coding, neurotoxic symptoms, mood factors, sedation, perception of cognitive performance, and other quality-of-life perceptions. Comparison of carbamazepine with the nondrug average revealed significantly better performance for nondrug average on 24 (62%) variables but none for carbamazepine. Comparison of lamotrigine with nondrug average revealed better performance on one (2.5%) variable for nondrug average and on one (2.5%) variable for lamotrigine. Conclusion: Lamotrigine produces significantly fewer untoward cognitive and behavioral effects than carbamazepine at the dosages used in this study.