Teratogenic effects of antiepileptic medications. 2009

Torbjörn Tomson, and Dina Battino
Department of Clinical Neuroscience Karolinska Institutet, Stockholm, Sweden; Department of Neurology, Karolinska Hospital, SE-171 76 Stockholm, Sweden. Electronic address: torbjorn.tomson@karolinska.se.

Data on clinical teratogenicity are at best derived from carefully conducted observational studies, whereas randomized, controlled trials have no place in this research area. We can only expect level B recommendations and lower. New relevant information has become available during the last 5 years on pregnancy outcomes with 3 of the most frequently used AEDs: carbamazepine, valproate, and lamotrigine. It seems that birth defect rates with arbamazepine monotherapy are lower than previously thought. In some large studies rates are only marginally increased compared with different control populations. More recent data do not suggest adverse effects of carbamazepine on cognitive development. The overall prevalence of malformations in association with lamotrigine exposure seems to be similar to that of carbamazepine. The only available prospective study on cognition does not indicate any adverse effects of lamotrigine. Malformation rates with valproate have consistently been found to be 2 to 3 times higher compared with carbamazepine or lamotrigine. More limited data also suggest adverse effects of high doses of valproate on cognitive development of the exposed child. For newer generation AEDs other than lamotrigine, data are still too limited to determine the risks for birth defects and are nonexisting with respect to possible adverse effects on cognitive development. Doses are important, and evidence is lacking for higher risks with valproate compared with other AEDs if doses are less than 800 to 1000 mg/d. Confounding factors contribute to some of the apparent differences between AEDs in pregnancy outcomes, and more data are needed, particularly concerning cognitive outcomes and specific birth defects. Based on these observations, valproate should not be a first-line AED for women who are considering pregnancy. In this situation this drug is best avoided if other effective but safer AEDs can be found for each individual woman's seizure disorder. Based on pregnancy outcome data, carbamazepine seems comparatively safe and a reasonable first-line choice in localization-related epilepsy. Alternatives are less clear in idiopathic generalized epilepsies. Lamotrigine seems comparatively safe, but its use in pregnancy is complicated by pharmacokinetic changes and risks of breakthrough seizures. The experience with use of levetiracetam and topiramate during pregnancy is still insufficient. Any attempt to change drugs should be completed and evaluated before conception; withdrawals or other major changes should be avoided during pregnancy. These conclusions are largely in line with the recently published report of the Quality Standards Subcommittee and Therapeutics and Technology Subcommittee of the American Academy of Neurology and the American Epilepsy Society.

UI MeSH Term Description Entries
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D004827 Epilepsy A disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology (e.g., post-traumatic), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal patterns (e.g., nocturnal epilepsy). (From Adams et al., Principles of Neurology, 6th ed, p313) Aura,Awakening Epilepsy,Seizure Disorder,Epilepsy, Cryptogenic,Auras,Cryptogenic Epilepsies,Cryptogenic Epilepsy,Epilepsies,Epilepsies, Cryptogenic,Epilepsy, Awakening,Seizure Disorders
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000014 Abnormalities, Drug-Induced Congenital abnormalities caused by medicinal substances or drugs of abuse given to or taken by the mother, or to which she is inadvertently exposed during the manufacture of such substances. The concept excludes abnormalities resulting from exposure to non-medicinal chemicals in the environment. Drug-Induced Abnormalities,Abnormalities, Drug Induced,Abnormality, Drug-Induced,Drug Induced Abnormalities,Drug-Induced Abnormality
D000927 Anticonvulsants Drugs used to prevent SEIZURES or reduce their severity. Anticonvulsant,Anticonvulsant Drug,Anticonvulsive Agent,Anticonvulsive Drug,Antiepileptic,Antiepileptic Agent,Antiepileptic Agents,Antiepileptic Drug,Anticonvulsant Drugs,Anticonvulsive Agents,Anticonvulsive Drugs,Antiepileptic Drugs,Antiepileptics,Agent, Anticonvulsive,Agent, Antiepileptic,Agents, Anticonvulsive,Agents, Antiepileptic,Drug, Anticonvulsant,Drug, Anticonvulsive,Drug, Antiepileptic,Drugs, Anticonvulsant,Drugs, Anticonvulsive,Drugs, Antiepileptic
D013723 Teratogens An agent that causes the production of physical defects in the developing embryo. Embryotoxins,Fetotoxins,Teratogen

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