Parental epilepsy, anticonvulsant drugs, and reproductive outcome: epidemiologic and experimental findings spanning three decades; 1: Animal studies

Abstract

In conclusion, it is clear that the experimental animal literature has been extremely beneficial in validating the teratogenicity of selected anticonvulsant drugs such as phenytoin and valproic acid, and in providing much needed information on pharmacokinetic parameters that are involved in altering normal embryogenesis. Continued efforts are needed to further elucidate the mechanism of teratogenic action for these drugs. It is clear from the work on phenytoin that reactive intermediates are important, and care must be taken to either avoid drug therapies that promote the formation of or inhibit the rapid degradation of toxic oxidative metabolites. For valproic acid and carbamazepine the pathogenesis of congenital defects remains much less defined. Until adequate information is ascertained on just how antiepileptic drugs disrupt normal development, it will be difficult, if not impossible, to develop either alternative medications or treatment strategies that maximize clinical effectiveness without the risk of an adverse pregnancy outcome. Such information emanating from animal studies shall, hopefully, be available in the not-too-distant future.