Teratogenicity of antiepileptic dual therapy

Keni, Ravish R.; Jose, Manna; Sarma, P. Sankara; Thomas, Sanjeev V

doi:10.1212/wnl.0000000000005031

Cited by 35 publications

(27 citation statements)

References 7 publications

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“…The Kerala study 66 has identified a signal of increased MCM risk after in utero exposure to clobazam, based on two MCM cases from nine pregnancies (MCM rate of 22.2%, 95% CI: 6.3–54.7). A subsequent study 67 from Kerala reported 12 MCMs from 125 polytherapy clobazam exposures (MCM rate of 9.6%), and 3 MCMs from 38 clonazepam polytherapy exposures (MCM rate of 7.9%). A French healthcare database cohort study 68 of 1,886,825 pregnancies identified a signal for microcephaly among 980 exposures to clonazepam.…”

Section: Monotherapymentioning

confidence: 99%

Preventing Teratogenicity in Women with Epilepsy

2022

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Over the last 50 years there has been a significant increase in our understanding of the issues faced by women with epilepsy, in both planning and undertaking pregnancy. The risks of teratogenicity associated with antiseizure medications have emerged slowly. The major pregnancy registers have substantially contributed to our knowledge about teratogenic risk associated with the commonly used antiseizure medications. However, there are substantial gaps in our knowledge about the potential risks associated with many third-generation drugs. The remit of the pregnancy registers and the wider research focus has moved beyond anatomical major congenital malformations. Increasingly neurodevelopmental and behavioral abnormalities have been investigated after in utero exposure to antiseizure medications. Public health approaches can help reduce the risk of teratogenicity. However, neurologists still have a vital role in reducing the risk of teratogenicity at an individual level for women attending their clinic. They also have responsibility to ensure that women with epilepsy are aware of the rationale for the different available options.

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Section: Monotherapymentioning

confidence: 99%

Preventing Teratogenicity in Women with Epilepsy

2022

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“…86 As a matter of fact, combination of sodium of valproate or topiramate is an independent risk factor of major congenital malformations. 87 Lastly, patients' comorbidities must carefully be screened. Without going into an exhaustive list, some frequent examples can be highlighted.…”

Section: Choosing Asd Upon Their Safety Profile?mentioning

confidence: 99%

“… 86 As a matter of fact, combination of sodium of valproate or topiramate is an independent risk factor of major congenital malformations. 87 …”

Section: Pharmacological Managementmentioning

confidence: 99%

Clinical Management of Drug Resistant Epilepsy: A Review on Current Strategies

Guéry

Rheims

2021

NDT

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Drug resistant epilepsy (DRE) is defined as the persistence of seizures despite at least two syndrome-adapted antiseizure drugs (ASD) used at efficacious daily dose. Despite the increasing number of available ASD, about a third of patients with epilepsy still suffer from drug resistance. Several factors are associated with the risk of evolution to DRE in patients with newly diagnosed epilepsy, including epilepsy onset in the infancy, intellectual disability, symptomatic epilepsy and abnormal neurological exam. Pharmacological management often consists in ASD polytherapy. However, because quality of life is driven by several factors in patients with DRE, including the tolerability of the treatment, ASD management should try to optimize efficacy while anticipating the risks of drug-related adverse events. All patients with DRE should be evaluated at least once in a tertiary epilepsy center, especially to discuss eligibility for non-pharmacological therapies. This is of paramount importance in patients with drug resistant focal epilepsy in whom epilepsy surgery can result in long-term seizure freedom. Vagus nerve stimulation, deep brain stimulation or cortical stimulation can also improve seizure control. Lastly, considering the effect of DRE on psychologic status and social integration, comprehensive care adaptations are always needed in order to improve patients' quality of life.

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“…The Kerala (India) Registry of Epilepsy and Pregnancy, established in 1998, published its findings of 1021 monotherapy and 368 dual AED exposures in pregnancy through 2013. 9 The AEDs used most commonly were carbamazepine, valproate, phenobarbital, and clobazam. The MCMs occurred in 70 (6.8%) of monotherapy and 44 (11%) of dual therapy exposed pregnancies.…”

Section: Commentarymentioning

confidence: 99%

Comparative Risk of Major Congenital Malformations With 8 Different Antiepileptic Drugs: A Prospective Cohort Study of the EURAP Registry

Vossler¹

2019

Epilepsy Curr

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Teratogenesis of 8 Antiepileptic Drugs in Multinational Experience Tomson T, Battino D, Bonizzoni E, Craig J, Lindhout D, Perucca E, Sabers A, Thomas SV, Vajda F for the EURAP Study Group. Lancet Neurol . 2018;17(6):530-538. doi: 10.1177/1535759719835353 Background: Evidence for the comparative teratogenic risk of antiepileptic drugs is insufficient, particularly in relation to the dosage used. Therefore, we aimed to compare the occurrence of major congenital malformations following prenatal exposure to the 8 most commonly used antiepileptic drugs in monotherapy. Methods: We did a longitudinal, prospective cohort study based on the EURAP international registry. We included data from pregnancies in women who were exposed to antiepileptic drug monotherapy at conception, prospectively identified from 42 countries contributing to EURAP. Follow-up data were obtained after each trimester, at birth, and 1 year after birth. The primary objective was to compare the risk of major congenital malformations assessed at 1 year after birth in offspring exposed prenatally to 1 of 8 commonly used antiepileptic drugs (carbamazepine, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, topiramate, and valproate) and, whenever a dose dependency was identified, to compare the risks at different dose ranges. Logistic regression was used to make direct comparisons between treatments after adjustment for potential confounders and prognostic factors. Findings: Between June 20, 1999, and May 20, 2016, 7555 prospective pregnancies met the eligibility criteria. Of those eligible, 7355 pregnancies were exposed to 1 of the 8 antiepileptic drugs for which the prevalence of major congenital malformations was 142 (10·3%) of 1381 pregnancies for valproate, 19 (6·5%) of 294 for phenobarbital, 8 (6·4%) of 125 for phenytoin, 107 (5·5%) of 1957 for carbamazepine, 6 (3·9%) of 152 for topiramate, 10 (3·0%) of 333 for oxcarbazepine, 74 (2·9%) of 2514 for lamotrigine, and 17 (2·8%) of 599 for levetiracetam. The prevalence of major congenital malformations increased with the dose at time of conception for carbamazepine (P = .0140), lamotrigine (P = .0145), phenobarbital (P = .0390), and valproate (P < .0001). After adjustment, multivariable analysis showed that the prevalence of major congenital malformations was significantly higher for all doses of carbamazepine and valproate as well as for phenobarbital at doses of more than 80 mg/d than for lamotrigine at doses of 325 mg/d or less. Valproate at doses of 650 mg/d or less was also associated with increased risk of major congenital malformations compared with levetiracetam at doses of 250 to 4000 mg/d (odds ratio [OR]: 2.43, 95% confidence interval [CI]: 1·30-4·55; P = .0069). Carbamazepine at doses of more than 700 mg/d was associated with increased risk of major congenital malformations compared to levetir...

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Teratogenicity of antiepileptic dual therapy

Abstract: Our data indicate that the excess risk of dual therapy over monotherapy is contributed largely by topiramate or valproate. The complex pharmacokinetic and pharmacodynamic effects of dual therapy adversely influence MCM risk.

Cited by 35 publications

References 7 publications

Preventing Teratogenicity in Women with Epilepsy

Preventing Teratogenicity in Women with Epilepsy

Clinical Management of Drug Resistant Epilepsy: A Review on Current Strategies

Comparative Risk of Major Congenital Malformations With 8 Different Antiepileptic Drugs: A Prospective Cohort Study of the EURAP Registry

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