Carbamazepine was first marketed in 1962 and for decades it was considered the drug of choice for focal epilepsy. Carbamazepine’s dominance as a first-line agent started to come into question with a large influx of new anti-seizure medications in the late 1990s and early 2000s. Many within the medical community were curious about how carbamazepine stood up against these newer-generation anti-seizure medications (ASMs). The landmark “Standard and New Antiepileptic Drugs” (SANAD) trial was performed to help answer this question.
The SANAD trial was a multi-armed outpatient unblinded randomized controlled trial that compared the relative efficacies and long-term effects of several ASMs. Arm A1 of the SANAD trial randomized 1721 patients with focal epilepsy into 5 different treatment groups. Each of these groups received one of the following ASMs as monotherapy: carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate. The dosing of ASMs was based on the clinicians’ judgment.
Patients in the study were aged four years or older. The primary outcomes included time to treatment failure (i.e. inadequate control, severe adverse effects, need for an additional ASM) and time to 12 months of seizure freedom. Other studied outcomes were time to first seizure, time to achieve 2-year remission, the incidence of clinically important adverse events, quality of life, and cost-effectiveness.
Final data analysis showed that the time to treatment failure for lamotrigine was significantly better than carbamazepine (hazard ratio 0.78 [95% CI 0.63–0.97]), gabapentin (0.65 [0.52–0.80]), and topiramate (0.64 [0.52–0.79]) and had a non-significant advantage over oxcarbazepine.
Time to 12-month remission was significantly better for carbamazepine than gabapentin (0.75 [0.63–0.90]) and had a non-significant advantage over all other ASMs. However, with long-term use (2-4 years) lamotrigine was found to be non-inferior to carbamazepine when looking at 12-month remission rates. Lastly, lamotrigine was also found to be a cost-effective alternative to carbamazepine.
The findings in this study arm lead to the increased utilization of lamotrigine as a first-line treatment for patients with focal onset seizures.
Review the landmark article here!
Learn more about lamotrigine here!
References:
- Marson AG, Al-Kharusi AM, Alwaidh M, et al. The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial. Lancet 2007; 369: 1000–15.
- Marson AG, Al-Kharusi AM, Alwaidh M, et al. The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial. Lancet 2007; 369: 1016–26.
- Marson A, Burnside G, Appleton R, et al. The SANAD II study of the effectiveness and cost-effectiveness of valproate versus levetiracetam for newly diagnosed generalised and unclassifiable epilepsy: an open-label, non-inferiority, multicentre, phase 4, randomised controlled trial. Lancet 2021; 397: 1375–86.
