Antiepileptic drugs as human teratogens

Eadie, Mervyn J. (2008) Antiepileptic drugs as human teratogens. Expert Opinion on Drug Safety, 7 2: 195-209. doi:10.1517/14740338.7.2.195


Author Eadie, Mervyn J.
Title Antiepileptic drugs as human teratogens
Journal name Expert Opinion on Drug Safety   Check publisher's open access policy
ISSN 1474-0338
1744-764X
Publication date 2008-03-01
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1517/14740338.7.2.195
Open Access Status Not Open Access
Volume 7
Issue 2
Start page 195
End page 209
Total pages 15
Place of publication London, United Kingdom
Publisher Informa Healthcare
Language eng
Subject 2736 Pharmacology (medical)
Abstract Epilepsy is a serious and common neurological disorder for which effective and well tolerated new agents continue to be sought. While the assessment of potential antiepileptic agents in animals models of epilepsy poses few problems, such assessment in humans is fraught with methodological and ethical dilemmas.Before the introduction of controlled clinical trials, agents that were though to have antiepileptic potential were merely administered to patients with epilepsy and the effects observed. Nowadays, many controls are placed on the testing of all new pharmacological agents, including antiepileptic drugs.The simplest method of assessing the efficacy of a new antiepileptic agent in humans is in a monotherapy, placebo-controlled trial. However, such a trial design poses serious ethical and moral issues due to the importance of achieving early optimal control of epileptic seizures in patients. Because of these difficulties, placebo-controlled monotherapy trials are rarely performed. Instead, add-on and crossover designs are used, each of which has its own inherent disadvantages. Thus, the ideal trial design which allows accurate and simple assessment of the efficacy of a new antiepileptic agent has still to be developed.
Formatted abstract
Background: There is still uncertainty concerning the risk of fetal malformation associated with the intake of various individual antiepileptic drugs in pregnant women. Objective: To assess the better-quality available evidence concerning the fetal hazards from exposure to antiepileptic drug monotherapy during human pregnancy. Method: Examination of the available English language literature, particularly that dealing with individual antiepileptic drugs used in monotherapy, in the larger case series with better-quality internal comparison data. Conclusions: There is reasonable evidence that valproate is a significant teratogen during therapeutic use in women; the other older antiepileptic drugs (phenobarbitone, phenytoin, carbamazepine) probably have some teratogenic potential, but less than valproate; the situation regarding the more recently marketed antiepileptic drugs is not yet clear.
Keyword Antiepileptic drugs
Malformations
Pregnancy
Teratogenesis
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collection: School of Medicine Publications
 
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