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The choice of antiseizure medication in generalized epilepsy is particularly challenging because efficacy must be balanced against reproductive safety. SANAD II compared valproate with levetiracetam as first-line treatment in children and adults with newly diagnosed generalized or unclassified epilepsy. In the intention-to-treat analysis, levetiracetam did not meet the predefined non-inferiority margin for 12-month seizure remission. In per-protocol analysis, valproate was superior for remission and was also associated with a lower risk of treatment failure. These findings are important because levetiracetam has been widely adopted as an alternative to valproate, partly because of concerns about valproate exposure during pregnancy. The trial does not remove those safety concerns; rather, it quantifies the efficacy trade-off. For HCPs, the clinical decision should therefore balance seizure control with reproductive potential, teratogenic risk and patient preference. The study is especially relevant to women who may become pregnant, where a less effective alternative may still be preferred in some circumstances. The key lesson is that antiseizure prescribing should be individualised and should explicitly address both efficacy and reproductive risk.
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The choice of antiseizure medication in generalized epilepsy is particularly challenging because efficacy must be balanced against reproductive safety. SANAD II compared valproate with levetiracetam as first-line treatment in children and adults with newly diagnosed generalized or unclassified epilepsy. In the intention-to-treat analysis, levetiracetam did not meet the predefined non-inferiority margin for 12-month seizure remission. In per-protocol analysis, valproate was superior for remission and was also associated with a lower risk of treatment failure. These findings are important because levetiracetam has been widely adopted as an alternative to valproate, partly because of concerns about valproate exposure during pregnancy. The trial does not remove those safety concerns; rather, it quantifies the efficacy trade-off. For HCPs, the clinical decision should therefore balance seizure control with reproductive potential, teratogenic risk and patient preference. The study is especially relevant to women who may become pregnant, where a less effective alternative may still be preferred in some circumstances. The key lesson is that antiseizure prescribing should be individualised and should explicitly address both efficacy and reproductive risk.
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