The Pharmaceutical Journal
Vol 278 No 7446 p391
7 April 2007

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Study clarifies first-choice treatment options for epilepsy

Lamotrigine should be the drug of first choice to treat most patients with partial epilepsy, and valproate should remain first-line treatment for those with generalised and unclassifiable epilepsy, according to two articles published in The Lancet (2007;369:1000 and 1016). During the unblinded, randomised controlled study, known as SANAD (standard and new antiepileptic drugs), doctors were allowed to choose the dose and preparation of the allocated drug.

Arm A of SANAD recruited 1,712 patients and compared carbamazepine with gabapentin, lamotrigine, oxcarbazepine and topiramate for patients with partial epilepsy.

For time to treatment failure, lamotrigine was found to be better than carbamazepine (hazard ratio 0.78, 95 per cent confidence interval 0.63–0.97), gabapentin (0.65, 0.52–0.80) and topiramate (0.64, 0.52–0.79). For time to 12-month remission, the results suggest that lamotrigine is as good as carbamazepine.

Arm B recruited 716 patients and compared valproate with lamotrigine and topiramate for patients with generalised onset seizures and seizures that are difficult to classify.

The researchers found that valproate is better tolerated than topiramate and more efficacious than lamotrigine and say it should remain as first-line therapy. However, they emphasise that there will always be circumstances, such as pregnancy, that would favour the choice of an alternative drug.

The researchers highlight that, since the study was designed, more antiepileptic drugs have been licensed in the UK and the same questions apply to these as to the drugs studied in SANAD.

The author of an accompanying editorial (ibid, p970), comments that SANAD was too small to address even common serious adverse events. He recommends that it might be wiser to conclude that lamotrigine is the drug of first choice in patients with partial seizures, and valproate for patients with generalised or unclassified seizures in the absence of factors that would lead to an alternative choice.