The SANAD II study of the effectiveness and cost-effectiveness of levetiracetam, zonisamide, or lamotrigine for newly diagnosed focal epilepsy: an open-label, non-inferiority, multicentre, phase 4, randomised controlled trial

SPS commentary:

The researchers suggest these findings do not support the use of levetiracetam or zonisamide as first-line treatments for patients with focal epilepsy. Lamotrigine should remain a first-line treatment for patients with focal epilepsy and should be the standard treatment in future trials.

A commentary notes that since 1990, many new antiseizure medications have been launched, many of which have been licensed on the basis of evidence from add-on therapy in resistant epilepsies; there have been few head-to-head comparative data in patients who are newly diagnosed. Standard and New Antiepileptic Drugs (SANAD) I, the first SANAD trial, provided the first comprehensive data to address this question; lamotrigine was shown to be superior to carbamazepine, gabapentin, oxcarbazepine, and topiramate in time to treatment failure, and valproate was a clinically and cost-effective alternative to lamotrigine or topiramate. Since these trials were done, other medications have been licensed for use, and levetiracetam has been increasingly considered a safe alternative in the treatment of both focal and generalised epilepsies, despite few head-to-head comparative data. In The Lancet, SANAD II—two pragmatic, open-label, randomised trials provide useful data in addressing this issue.

According to the commentary, the trials recruited adults and children aged 5 years and older. In the focal epilepsy study, low numbers of children (155 [16%] of 990 total participants) were recruited, probably related to the fact zonisamide is not licensed in this age group. It also needs to be acknowledged that other seizure medications have now been licensed, specifically for patients with focal seizures that were not included in the studies. It concludes nonetheless, that the pragmatic design of the studies provides useful data for treatment choice.

The other RCT (n=520) found that levetiracetam did not meet definition of non-inferiority for time to 12-month remission vs. valproate and it was inferior for times to treatment failure, 2-year remission from seizures, and first subsequent seizure, was not found to be a cost-effective alternative.