Developmental neurotoxicology of antiepileptic drugs

Of the more than 30 drugs approved for the treatment of seizure disorders, only 6 medications have been evaluated for their safety in regard to the developing human brain and behavior following human gestational exposure. The clinical research findings for these medications (phenobarbital, phenytoin, carbamazepine, valproic acid, lamotrigine, and levetiracetam) when used in the monotherapeutic treatment of pregnant women with seizure disorders are reviewed, and from studies using animal models, information is presented on the nature and origin of the effects on the developing nervous system. This review suggests that valproic acid is the most potent with respect to developmental neurotoxicity and that phenobarbital and carbamazepine are also associated with adverse neurobehavioral teratogenic effects. Limited data on the newest medications, lamotrigine and levetiracetam, suggest relative safety. The neurobehavioral effects appear to be mediated by teratogenic impact upon critical developmental processes of neurogenesis, migration, apoptosis, and synaptogenesis.