Teratogenicity of antiepileptic medications.
Antiepileptic drugs (AEDs) are frequently used to treat several conditions that are common in women of childbearing age, including epilepsy, headaches, and mood disorders. Moreover, as in the case of epilepsy and severe psychiatric disease, clinicians frequently do not have the option of stopping these medications or switching to another class of drugs. Overall, AEDs have been associated with an increased risk of major congenital malformations, minor anomalies, specific congenital syndromes, and developmental disorders seen in childhood. However, the differential effects of individual AEDs remain uncertain. Data are accumulating which strongly suggest that these risks are highest in patients receiving polypharmacy and valproate. There is also modest evidence to suggest an increased risk for phenobarbital. While other older AEDs appear to carry some teratogenic risk, there is not adequate evidence to further stratify their risk. Clinical and basic science research regarding newer AEDs suggests equivalent, if not safer, profiles compared with older AEDs, but these data are inconclusive. Management of women with epilepsy should include a discussion of these risks, prophylactic treatment with folic acid, and the minimal use of polypharmacy and valproate needed to maintain optimum seizure control.
Kluger
Benzi M
BM
Department of Neurology, University of Florida, Gainesville, Florida 32610, USA.
Meador
Kimford J
KJ
D000014:Abnormalities, Drug-Induced / Q000517:prevention & control*; D000927:Anticonvulsants / Q000009:adverse effects*; D004347:Drug Interactions / Q000502:physiology; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use; D006801:Humans; D011247:Pregnancy; D018570:Risk Assessment; D012307:Risk Factors; D014635:Valproic Acid / Q000009:adverse effects
D000927:Anticonvulsants; D014635:Valproic Acid; D005492:Folic Acid
Epilepsia. 2001 Jun;42(6):750-3
11422330
Neurol Clin. 2004 Nov;22(4):799-820
15474768
JAMA. 1994 Mar 9;271(10):767-70
7509419
Neurology. 2006 Nov 28;67(10):1876-9
17130430
Neurology. 2006 Aug 8;67(3):407-12
16894099
Neurology. 1998 Oct;51(4):944-8
9781510
Birth Defects Res A Clin Mol Teratol. 2004 Aug;70(8):534-6
15329832
Semin Neurol. 2002 Sep;22(3):299-308
12528055
Pediatr Neurosurg. 1995;23(6):311-6
8744000
MMWR Recomm Rep. 1992 Sep 11;41(RR-14):1-7
1522835
Acta Paedopsychiatr. 1963 Nov-Dec;30:401-5
14093746
CMAJ. 2002 Aug 6;167(3):265-73
12186175
An Pediatr (Barc). 2005 Oct;63(4):363-5
16219257
N Engl J Med. 2001 Apr 12;344(15):1132-8
11297704
Epilepsy Behav. 2003 Jun;4(3):310-7
12791334
JAMA. 1995 Nov 15;274(19):1518-25
7474220
Paediatr Drugs. 2001;3(1):1-8
11220402
Epilepsia. 1992;33 Suppl 4:S41-8
1425493
Clin Genet. 1999 Sep;56(3):216-20
10563481
Nat Rev Genet. 2001 Jun;2(6):458-68
11389462
Epilepsia. 1997 Sep;38(9):981-90
9579936
Seizure. 2007 Jan;16(1):87-93
17269155
Epilepsia. 2007 Jun;48(6):1207-10
17381445
Am J Med Genet. 1988 Jan;29(1):171-85
3125743
Neurol Clin. 1994 Nov;12(4):773-88
7845342
Neurology. 2005 Mar 22;64(6):955-60
15781807
Neurology. 2005 Mar 22;64(6):961-5
15781808
BMJ. 1998 Sep 26;317(7162):839-43
9748174
Crit Rev Toxicol. 2005 Oct-Nov;35(8-9):727-38
16417040
Arq Neuropsiquiatr. 2001 Jun;59(2-B):362-4
11460180
Nat Rev Neurosci. 2004 Jul;5(7):553-64
15208697
N Engl J Med. 1989 Jun 22;320(25):1661-6
2725616
Acta Paediatr. 2004 Feb;93(2):174-6
15046269
Acta Neurol Scand. 2005 Sep;112(3):137-43
16097954
Neurology. 2003 Sep 1;61(6 Suppl 2):S23-6
14504306
Acta Psychiatr Scand. 2005 Aug;112(2):88-96
15992389
Neurology. 2003 Jun 10;60(11 Suppl 4):S31-8
12796519
Curr Neurol Neurosci Rep. 2006 Jul;6(4):341-6
16822356
Lancet. 1985 Oct 5;2(8458):746-9
2864485
Cell Mol Life Sci. 2006 Feb;63(4):399-413
16389461
CNS Drugs. 2002;16(11):755-64
12383031
Lancet. 1982 Nov 13;2(8307):1096
6127554
Neurology. 1998 Sep;51(3):904-6
9748057
JAMA. 1994 Sep 21;272(11):850-1
7521402
Arch Neurol. 2004 May;61(5):673-8
15148143
Epilepsy Res. 2003 Jan;52(3):147-87
12536051
J Pediatr. 1975 Aug;87(2):285-90
50428
Genes Dev. 1997 Dec 15;11(24):3286-305
9407023
Epilepsia. 1994;35 Suppl 4:S19-28
8174516
Epilepsia. 2006 Dec;47(12):1999-2010
17201696
Am J Obstet Gynecol. 1999 Oct;181(4):828-34
10521737
Ann Intern Med. 2007 Sep 18;147(6):370-6
17876020
Acta Neurol Scand. 1992 Jan;85(1):39-43
1546532
Lancet Neurol. 2005 Nov;4(11):781-6
16239185
QJM. 1997 Feb;90(2):111-5
9068801
J Med Genet. 2002 Apr;39(4):251-9
11950853
J Neurol Neurosurg Psychiatry. 2004 Nov;75(11):1575-83
15491979
Drug Saf. 2005;28(8):695-706
16048355
Neurology. 1992 Apr;42(4 Suppl 5):32-42
1574174
Am J Clin Nutr. 2007 Jan;85(1):285S-288S
17209211
Br Med J. 1973 May 26;2(5864):442-8
4712481
Reprod Toxicol. 2006 Aug;22(2):214-26
16621443
Perspect Sex Reprod Health. 2006 Jun;38(2):90-6
16772190
Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):15089-94
12417760
Neurology. 2003 Feb 25;60(4):575-9
12601095
J Neurol Neurosurg Psychiatry. 2006 Feb;77(2):193-8
16157661
Curr Med Res Opin. 2005 May;21(5):693-701
15969868
Epilepsia. 1993 Jul-Aug;34(4):588-9
8330564
Annu Rev Pharmacol Toxicol. 2002;42:181-208
11807170
Neurology. 2003 Sep 1;61(6 Suppl 2):S35-42
14504308
Drug Saf. 2004;27(3):197-202
14756581
Neurology. 2005 Jun 14;64(11):1874-8
15955936