Lamotrigine is the best option for patients with newly diagnosed focal epilepsy

According to study results published in the Lancet, lamotrigine is the best first-line treatment option for patients newly diagnosed with focal epilepsy.

Although levetiracetam and zonisamide are approved for use in patients with focal epilepsy, there are limited data on the recommended initial treatment for newly diagnosed patients. The aim of the current study was to determine the long-term effectiveness and cost-effectiveness of lamotrigine compared to levetiracetam and zonisamide.

This randomized, open, controlled trial enrolled adults and children 5 years and older from neurology services across the UK with two or more unprovoked partial seizures. Patients were randomly given 1: 1: 1 lamotrigine, levetiracetam, or zonisamide.

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All participants were included in the intention-to-treat analysis, but the per-protocol analysis excluded participants with major protocol deviations and those who were later not diagnosed with epilepsy. The study was designed to assess the non-inferiority of levetiracetam and zonisamide to lamotrigine for the primary outcome of time to 12 month remission.

The sample consisted of 990 patients (mean age 39.3 years; 57% boys and men). Of these, 330 patients randomly received lamotrigine, 332 received levetiracetam, and 328 received zonisamide.

In the intention-to-treat analysis, levetiracetam did not meet the non-inferiority criteria for a 12-month remission compared to lamotrigine (hazard ratio) [HR]1.18; 97.5% CI, 0.95-1.47; Non-inferiority margin, 1.314), but zonisamide met the criteria (HR, 1.03; 97.5% CI, 0.83-1.28). In the protocol analysis, the 12-month remission was better with lamotrigine than with levetiracetam (HR 1.32; 97.5% CI 1.05-1.66) or zonisamide (HR 1.37; 97.5% CI 1.08 -1.73). Lamotrigine was superior to both drugs in cost-benefit analyzes based on differences between treatment groups in terms of cost and quality-adjusted life years.

The study researchers observed that 33% of lamotrigine-treated patients, 44% of levetiracetam-initiated patients, and 45% of zonisamide-initiated patients reported side effects. There were 37 deaths during the study: 15 in the lamotrigine-treated patients, 12 in the levetiracetam-treated patients, and 10 in the participants who initiated zonisamide.

The study had several limitations, including the use of seizure diaries to capture data with potential bias, a relatively small number of patients under the age of 18, potential systematic bias due to the maintenance doses chosen, a low response rate to quality of life questionnaires, and no data Effects of Newer Antiepileptic Drugs.

“Our results support the continued use of lamotrigine as an initial treatment for patients with focal epilepsy and its use as the standard comparator in future comparative studies,” concluded the study researchers.

Disclosure: Some authors of the study stated links to the pharmaceutical industry. For a full list of the authors’ information, see the original reference.


Marson A., Burnside G., Appleton R. et al. The SANAD II study on the efficacy and cost-effectiveness of levetiracetam, zonisamide or lamotrigine in newly diagnosed focal epilepsy: an open, multicenter, phase 4 study without inferiority, randomized and controlled. Lancet. 2021, April 10; 397 (10282): 1363-1374. doi: 10.1016 / S0140-6736 (21) 00247-6

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