Congenital malformations due to antiepileptic drugs

Kaneko, Sunao; Battino, Dina; Andermann, Eva; Wada, Kazumaru; Kan, Rumiko; Takeda, Akio; Nakane, Yoshibumi; Ogawa, Yoshihiro; Avanzini, G.; Fumarola, C.; Granata, Tiziana; Molteni, Francesco; Pardi, Giorgio; Minotti, Lorella; Canger, R.; Dansky, Linda V.; Oguni, Miyako; Lopes-Cendas, I; Sherwin, Allan L.; Andermann, F.; Seni, Marie‐Hélène; Okada, Motohiro; Teranishi, Takashi

doi:10.1016/s0920-1211(98)00084-9

Cited by 334 publications

(230 citation statements)

References 26 publications

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“…Thus, the teratogenicity of PHT has been established amongst clinicians and basic scientists for almost 40 years. As is often the case, some studies found significant associations between in utero PHT exposure and MCMs [Kaneko et al, 1999;Vajda et al, 2006;Wide et al, 2004], while others failed to find such associations [Artama et al, 2005;Morrow et al, 2006;Vajda et al, 2007Vajda et al, , 2012 (Table II).…”

Section: Antiepileptic Drugsmentioning

confidence: 83%

“…Major malformations affected 4.5% and 8.6% of these infants, respectively. Other authors observed major birth defects in 3.2 -7.8% of pregnancies complicated by AED monotherapy, and 6.0 -9.3% in AED polytherapy [Artama et al, Canger et al, 1999;Cunnington et al, 2005;Kaaja et al, 2003;Kaneko et al, 1999;Mawer et al, 2010;Morrow et al, 2006;Samren et al 1999;Wide et al, 2004;Wyszynski et al, 2004;. The meta analysis of 26 studies compiled by Tomson and Battino revealed a major congenital malformation (MCM) rate of 6.1% in offspring of women with epilepsy who were treated with AEDs, 2.8% among children of women with untreated epilepsy, and 2.2% in the healthy control group .…”

Section: Introductionmentioning

confidence: 99%

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Antiepileptic Drugs and Pregnancy Outcomes

Wlodarczyk

Palacios

George³

et al. 2012

Obstetrical &Amp; Gynecological Survey

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The treatment of epilepsy in women of reproductive age remains a clinical challenge. While most women with epilepsy require anticonvulsant drugs for adequate control of their seizures, the teratogenicity associated with some antiepileptic drugs is a risk that needs to be carefully addressed. Antiepileptic medications are also used to treat an ever broadening range of medical conditions such as bipolar disorder, migraine prophylaxis, cancer and neuropathic pain. Despite the fact that the majority of pregnancies of women with epilepsy who are receiving pharmacological treatment are normal, studies have demonstrated that the risk of having a pregnancy complicated by a major congenital malformation is doubled when comparing the risk of untreated pregnancies. Furthermore, when antiepileptic drugs (AEDs) are used in polytherapy regimens, the risk is tripled, especially when valproic acid (VPA) is included. However, it should be noted that the risks are specific for each anticonvulsant drug. Some investigations have suggested that the risk of teratogenicity is increased in a dose-dependent manner. More recent studies have reported that in utero exposure to AEDs can have detrimental effects on the cognitive functions and language skills in later stages of life. In fact, the FDA just issued a safety announcement on the impact of VPA on cognition (Safety Announcement 6-30-2011). The purpose of this document is to review the most commonly used compounds in the treatment of women with epilepsy, and to provide information on the latest experimental and human epidemiological studies of the effects of antiepileptic drugs in the exposed embryos.

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Section: Antiepileptic Drugsmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Antiepileptic Drugs and Pregnancy Outcomes

Wlodarczyk

Palacios

George³

et al. 2012

Obstetrical &Amp; Gynecological Survey

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“…Phenytoin is teratogenic. 24 The hepatic metabolism of PHT becomes saturated at moderate-to-high serum concentrations in an age-dependent fashion, which results in nonlinear pharmacokinetics. 25 Phenytoin induces hepatic enzymes, reducing serum concentrations of other hepatically metabolized AEDs such as CBZ, valproate (VPA), lamotrigine (LTG), and topiramate (TPM), as well as hormonal contraceptives.…”

Section: Phenytoinmentioning

confidence: 99%

Currently Available Antiepileptic Drugs

Schachter

2007

Neurotherapeutics

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Summary:Many new antiepileptic drugs (AEDs) have become available over the past 15 years. At the same time, the emphasis on treating patients with epilepsy has grown from stopping seizures to avoiding side effects and maximizing quality of life. This review summarizes currently available AEDs, and presents general treatment principles and guidelines for AED selection. Unfortunately, despite the increased treatment options of today, seizure freedom without side effects remains unattainable for too many patients with epilepsy. Consequently, there remains a significant need for further development of new therapies.

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“…Average behavioral seizure score ± SEM 25 1/7 5 ± 0 3.9 ± 0.5 a 4.4 ± 0.2 4.9 ± 0.1 4.9 ± 0.1 4.9 ± 0.1 37. 5 2/7 4.9 ± 0. 68.0 ± 6.7 38.6 ± 8.9 a 40.3 ± 9.4 a 50.9 ± 10.1 50.0 ± 3.5 a 66.1 ± 8.9…”

Section: Electrophysiologymentioning

confidence: 99%

Anticonvulsant Profile and Teratogenicity of N‐methyl‐tetramethylcyclopropyl Carboxamide: A New Antiepileptic Drug

et al. 2002

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Summary: Purpose:The studies presented here represent our efforts to investigate the anticonvulsant activity of N-methyltetramethylcyclopropyl carboxamide (M-TMCD) and its metabolite tetramethylcyclopropyl carboxamide (TMCD) in various animal (rodent) models of human epilepsy, and to evaluate their ability to induce neural tube defects (NTDs) and neurotoxicity.Methods: The anticonvulsant activity of M-TMCD and TMCD was determined after intraperitoneal (i.p.) administration to CF#1 mice, and either oral or i.p. administration to Sprague-Dawley rats. The ability of M-TMCD and TMCD to block electrical-, chemical-, or sensory-induced seizures was examined in eight animal models of epilepsy. The plasma and brain concentrations of M-TMCD and TMCD were determined in the CF#1 mice after i.p. administration. The induction of NTDs by M-TMCD and TMCD was evaluated after a single i.p. administration at day 8.5 of gestation in a highly inbred mouse strain (SWV) that is susceptible to valproic acidinduced neural tube defects.Results: In mice, M-TMCD afforded protection against maximal electroshock (MES)-induced, pentylenetetrazol (Metrazol)-induced, and bicuculline-induced seizures, as well as against 6-Hz "psychomotor" seizures and sound-induced seizures with ED 50 values of 99, 39, 81, 51, and 10 mg/kg, respectively. In rats, M-TMCD effectively prevented MES-and Metrazol-induced seizures and secondarily generalized seizures in hippocampal kindled rats (ED 50 values of 82, 45, and 39 mg/kg, respectively). Unlike M-TMCD, TMCD was active only against Metrazol-induced seizures in mice and rats (ED 50 values of 57 and 52 mg/kg, respectively). Neither M-TMCD nor TMCD was found to induce NTDs in SWV mice.Conclusions: The results obtained in this study show that M-TMCD is a broad-spectrum anticonvulsant drug that does not induce NTDs and support additional studies to evaluate its full therapeutic potential.

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Congenital malformations due to antiepileptic drugs

Cited by 334 publications

References 26 publications

Antiepileptic Drugs and Pregnancy Outcomes

Antiepileptic Drugs and Pregnancy Outcomes

Currently Available Antiepileptic Drugs

Anticonvulsant Profile and Teratogenicity of N‐methyl‐tetramethylcyclopropyl Carboxamide: A New Antiepileptic Drug

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