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SANAD II directly addressed an everyday epilepsy question: how do newer antiseizure medicines compare with established first-line therapy? In the focal-epilepsy trial, 990 participants were randomised to lamotrigine, levetiracetam or zonisamide. Levetiracetam did not meet the prespecified criteria for non-inferiority to lamotrigine for time to 12-month remission, while zonisamide met the non-inferiority criterion in the intention-to-treat analysis. In the per-protocol analysis, however, lamotrigine was superior to both newer treatments for the primary remission outcome, and treatment failure was less frequent with lamotrigine. Adverse reactions were also somewhat less common with lamotrigine. The trial was open-label, which may have influenced decisions about treatment failure or adverse effects. Nevertheless, its pragmatic design and long follow-up make it highly relevant to routine practice. For HCPs, the message is that newer drugs should not automatically displace established first-line therapy simply because they are newer or perceived as easier to use. Drug selection still depends on seizure type, comorbidity, reproductive considerations, tolerability and patient preference.

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SANAD II directly addressed an everyday epilepsy question: how do newer antiseizure medicines compare with established first-line therapy? In the focal-epilepsy trial, 990 participants were randomised to lamotrigine, levetiracetam or zonisamide. Levetiracetam did not meet the prespecified criteria for non-inferiority to lamotrigine for time to 12-month remission, while zonisamide met the non-inferiority criterion in the intention-to-treat analysis. In the per-protocol analysis, however, lamotrigine was superior to both newer treatments for the primary remission outcome, and treatment failure was less frequent with lamotrigine. Adverse reactions were also somewhat less common with lamotrigine. The trial was open-label, which may have influenced decisions about treatment failure or adverse effects. Nevertheless, its pragmatic design and long follow-up make it highly relevant to routine practice. For HCPs, the message is that newer drugs should not automatically displace established first-line therapy simply because they are newer or perceived as easier to use. Drug selection still depends on seizure type, comorbidity, reproductive considerations, tolerability and patient preference.
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