Do Alternative Medications for Epilepsy in Pregnancy Reduce the Risk for Major Malformations vs Valproate?
BACKGROUND AND PURPOSE:
Cohen et al. (Neurology, 2024) described first trimester use of antiseizure medication (ASM) combinations as alternatives to valproate to reduce the risk for major congenital malformations (MCM)
Population-based cohort study
Denmark | Finland | Iceland | Norway | Sweden | US | Australia
From 2000 to 2020
In Denmark | Finland | Iceland | Norway | Sweden | US | Australia from 2000 to 2020
Combination ASM vs valproate monotherapy in the first trimester
Low-dose valproate plus lamotrigine or levetiracetam vs high-dose valproate (≥1,000 mg/d)
Regression analysis with propensity score weighting was used to calculate adjusted risk ratio
Results were pooled with fixed-effects meta-analysis
Major congenital malformations
Lamotrigine and levetiracetam: 788
Lamotrigine and topiramate: 291
Levetiracetam and topiramate: 208
Levetiracetam and zonisamide: 91
Lamotrigine and zonisamide: 80
Compared to valproate monotherapy, lamotrigine-levetiracetam duotherapy was associated with a reduced risk of MCM
aRR 0.41 (95% CI, 0.24 to 0.69)
There was no significant difference between valproate monotherapy and lamotrigine-topiramate duotherapy
aRR 1.26 (95% CI, 0.71 to 2.23)
Duotherapy combinations containing low-dose valproate were infrequent
Comparisons with high-dose valproate monotherapy were inconclusive but suggested a lower risk for combination therapy
Other combinations were too rare
Compared to valproate monotherapy, lamotrigine-levetiracetam duotherapy in first trimester was associated with a 60% reduced risk of MCM
There was no risk reduction with lamotrigine-topiramate duotherapy
The authors state
Duotherapy with lamotrigine and levetiracetam may be favored to treat epilepsy in people with childbearing potential compared with valproate regarding MCM, but whether this combination is as effective as valproate remains to be determined
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