Effect of valproate on cognitive functioning. Comparison with carbamazepine. The Department of Veterans Affairs Epilepsy Cooperative Study 264 Group.

OBJECTIVE

To assess the effects of carbamazepine vs valproate sodium on cognitive functioning in patients with epilepsy compared with normal control subjects.

DESIGN

Patients with recently diagnosed, previously unmedicated seizures participated in a prospective randomized double-blind Department of Veterans Affairs multicenter study of the efficacy and toxicity of carbamazepine vs valproate.

MAIN OUTCOME MEASURE

A behavioral toxicity battery was administered prior to treatment and again 6 and 12 months after the initiation of antiepileptic medication.

RESULTS

There were no significant differences in the effect of carbamazepine vs valproate on motor speed and coordination, memory, or concentration and mental flexibility, and there was no significant decline in neuropsychological performance from pretreatment baseline levels for either drug. No significant differences in performance were found between patients with low (mean, 52.8 micrograms/mL) vs high (mean, 94.4 micrograms/mL) serum valproate levels within the therapeutic range. Patients treated with either carbamazepine or valproate did not show practice effects experienced by normal controls, a finding that may reflect a subtle compromise in cognitive functioning.

CONCLUSION

The impact of carbamazepine and valproate monotherapy on cognitive functioning is similar: both drugs produce minimal negative effects compared with pretreatment baseline performance.