Teratogenicity of the newer antiepileptic drugs – the Australian experience

Vajda, Frank J. E.; Graham, Janet; Roten, Annie; Lander, C. M.; O’Brien, Terrence; Eadie, Mervyn J.

doi:10.1016/j.jocn.2011.08.003

Cited by 71 publications

(37 citation statements)

References 11 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: 81%

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: 81%

Antiepileptic Drugs and Pregnancy Outcomes

Wlodarczyk

Palacios

George³

et al. 2012

Obstetrical &Amp; Gynecological Survey

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“…Recent studies have reported that new generation AEDs are less teratogenic and have less cognitive impairment than traditional AEDs [15][16][17][18].…”

Section: Discussionmentioning

confidence: 99%

Effects of Lamotrigine and Topiramate on Brain Maturation and Cognitive Functions in Offspring of Pregnant Rats – Preliminary Study

Dağ¹,

Dağ²,

Baydaş³

et al. 2014

Adv Clin Exp Med

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Background. Antiepileptic drugs (AED) which are used to treat seizures in pregnant women, infants, and young children may cause cognitive impairment or other uncertain injury. However, the precise mechanisms responsible for the negative effects of new AEDs like lamotrigine (LTG) and topiramate (TPM) in the developing brain are still unclear. Objectives. To investigate the GFAP, NCAM and S100B levels in the whole brain of newborn rats on postnatal 1 day and in the hippocampus of adult rats to find out the effect of TPM and LTG on cognitive impairment and brain maturation. Material and Methods. Twenty eight pregnant rats were randomly divided into 7 groups with 4 animals in each group. The first group, receiving no drugs, was assigned as the control group. The study groups received intraperitoneal TPM or LTG injections in each trimester. Western blot analysis of the GFAP, NCAM and S100B was performed in the offspring. Behavioral tests were performed at postnatal day 75. Results. The rats in the TPM-I and TPM-III groups had a significant impairment in escape latency on the 5 th day as compared to the control rats in a Morris water maze test. In addition, in the expression of astrocyte derived markers, GFAP was upregulated, whereas S100β and NCAM were downregulated in the whole brain on postnatal day 1, in offspring exposed to LTG and TPM in utero. Conclusions. The detrimental effects of TPM and LTG appear to be confined particularly to the early stages of brain development. And TPM seems to have a partial role in the cognitive impairment (Adv Clin Exp Med 2014, 23, 5, 691-698).

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“…15 This drug may replace LTG in pregnant women with epilepsy, who require VPA for seizure control, but where high dose VPA needs to be avoided. The evidence for this is not yet available but levetiracetam combined with lower doses of VPA appears a possible option in this situation.…”

Section: Levetiracetammentioning

confidence: 99%

Dose issues in antiepileptic therapy

Vajda¹

2012

Journal of Clinical Neuroscience

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Teratogenicity of the newer antiepileptic drugs – the Australian experience

Cited by 71 publications

References 11 publications

Antiepileptic Drugs and Pregnancy Outcomes

Antiepileptic Drugs and Pregnancy Outcomes

Effects of Lamotrigine and Topiramate on Brain Maturation and Cognitive Functions in Offspring of Pregnant Rats – Preliminary Study

Dose issues in antiepileptic therapy

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