Epilepsy Drugs For Newly Diagnosed Patients: What’s Best?

April 13, 2021

Summary, originally published in MedPageToday

Valproate (Depakene) emerged as the best first-line choice for generalized epilepsy in a pragmatic study and lamotrigine (Lamictal) as the best first-line treatment for focal epilepsy, British researchers said.

The conclusions came from the phase IV open-label Standard and New Antiepileptic Drugs (SANAD II) study with two parts: a randomized trial of levetiracetam (Keppra) and valproate in newly diagnosed generalized epilepsy patients, and a randomized trial of levetiracetam, lamotrigine, and zonisamide (Zonegran) in newly diagnosed focal epilepsy patients. Results were published in separate papers in The Lancet.

In new patients with generalized or unclassified epilepsy, levetiracetam did not meet non-inferiority criteria compared with valproate in intention-to-treat analysis of time to 12-month remission (HR 1.19, 95% CI 0.96-1.47; non-inferiority margin 1.329), reported Anthony Marson, MD, of University of Liverpool in England, and co-authors. Treatment failure due to inadequate seizure control was more likely with levetiracetam, and a per-protocol analysis that took treatment failure into account found valproate to be superior (HR 1.68, 95% CI 1.30–2.15). Cost-effectiveness based on differences in costs and quality-adjusted life years found valproate to be superior.

“The available evidence now identifies valproate as more clinically and cost effective than both lamotrigine and levetiracetam,” Marson said in a statement. “Levetiracetam has been widely adopted in the U.K. and worldwide as a first-line treatment for focal epilepsy, but this should no longer be the case as it is neither clinically nor cost effective compared to lamotrigine,” he added.