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. 2021 Sep;144(3):288-295.
doi: 10.1111/ane.13446. Epub 2021 May 11.

Valproic acid use in fertile women with genetic generalized epilepsies

David Steinbart  1 , Verena Gaus  1 , Alexander B Kowski  1 , Martin Holtkamp  1
Affiliations

Valproic acid use in fertile women with genetic generalized epilepsies

David Steinbart et al. Acta Neurol Scand. 2021 Sep.

Abstract

Objectives: In genetic generalized epilepsies (GGE), valproic acid (VPA) is the most efficacious compound. However, due to teratogenicity and increased risk for impaired cognitive development after intrauterine exposure, its use in women of fertile age is strictly regulated but sometimes unavoidable.

Methods: All patients with GGE treated at the outpatient clinic of a tertiary epilepsy center with at least one visit between January 2015 and April 2020 were included in this retrospective study. The rate of women aged 18 to 49 years taking VPA was compared to that of men of the same age group and to women > 49 years. Furthermore, in each group, clinical variables associated with VPA use were sought.

Results: Twenty-eight out of 125 women of fertile age (22%) were treated with VPA, compared to 28 out of 56 men ≤ 49 years (50%; p = .002) and to 22 out of 40 female patients > 49 years (55%; p < .001). VPA dose was lower in fertile women compared to men, with no difference in seizure freedom rates. In women ≤ 49 years, multivariate analysis demonstrated age as the only variable independently associated with VPA use (OR 1.095; 95% CI 1.036-1.159). In the other two groups, no associated variables were identified.

Conclusions: Despite warnings with respect to teratogenicity and impaired cognitive development with VPA, from 2015 to 2020, almost every fourth women of fertile age with GGE received this compound. Inevitably lower VPA doses in these women seem sufficient for favorable seizure freedom rates.

Keywords: antiseizure medication; cognitive disabilities; defined daily dose; female patients; teratogenicity.

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References

REFERENCES

    1. Elger CE, Berkenfeld R. S1-Leitlinie Erster epileptischer Anfall und Epilepsien im Erwachsenenalter. Deutsche Gesellschaft für Neurologie. Published 2017. online: https://dgn.org/leitlinien/030-041-erster-epileptischer-anfall-und-epile.... Accessed January 06, 2021.
    1. NICE National Institute for Health and Care Excellence UK. Epilepsies : diagnosis and management. Clinical guideline. Published 2020. https://www.nice.org.uk/guidance/cg137. Accessed January 06, 2021.
    1. Scottish Intercollegiate Guidelines Network. Diagnosis and management of epilepsy in adults KEY TO EVIDENCE STATEMENTS AND GRADES OF RECOMMENDATIONS. SIGN 143. Published 2015. http://www.sign.ac.uk/pdf/SIGN143.pdf. Accessed January 06, 2021.
    1. Marson AG, Al-Kharusi AM, Alwaidh M, et al. The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial. Lancet. 2007;369(9566):1016-1026. https://doi.org/10.1016/S0140-6736(07)60461-9
    1. Tomson T, Battino D, Bonizzoni E, et al. Comparative risk of major congenital malformations with eight different antiepileptic drugs: a prospective cohort study of the EURAP registry. Lancet Neurol. 2018;17(6):530-538. https://doi.org/10.1016/S1474-4422(18)30107-8