In March a very important trial comparing anti-epileptic drugs (AEDs) reported its findings. The biggest study of epilepsy drugs ever carried out, it is also the first to directly compare currently available AEDs to each other.

It confirmed that, for most patients newly diagnosed with generalised epilepsy, sodium valproate, the standard drug, should be the first treatment tried. For partial seizures, a new drug, lamotrigine, was found to be more effective than the current standard, carbamazepine.

The Standard And New Anti-epileptic Drugs (SANAD) trial
Run by researchers at the University of Liverpool, the SANAD trial was divided into two parts. One compared all the drugs used for partial epilepsy to each other, and especially to the standard drug used for this condition, cabamazepine. The other part did the same for drugs for generalised (or unclassified) epilepsy, where the standard AED is sodium valproate.

Both arms looked at how well each AED controlled seizures, the drugs' side effect profiles, patients' quality of life, and cost. Patients were enrolled between January 1999 and August 2004 and followed up until early 2006. To get as close as possible to the real life situation, patients' doctors could adjust the dose or even change drugs if the first one didn't work (normally on trials this isn't allowed).

In order to measure efficacy, researchers recorded the time it took before a drug was judged not to work (poorer drugs will be changed more quickly and score low here), and the time it took for a patient to have a 12-month period of no seizures (more effective drugs score higher here). Other factors, such as the rate of serious side effects for each drug, were also included.

Partial epilepsy
A total of 1,721 patients in the partial epilepsy arm were randomly assigned to begin treatment on one of the four new drugs gabapentin, lamotrigine, oxcarbazepine or topiramate, or the standard older drug for this type of epilepsy, carbamazepine. Overall, lamotrigine had the lowest rate of "treatment failure", and a lower side effect rate than carbamazepine. Gabapentin and topiramate were the poorest performing drugs.

The authors, led by Dr Anthony Marson, concluded that lamotrigine was clinically better than the current standard carbamazepine for treating partial seizures.

Generalised epilepsy
Seven-hundred-and-sixteen patients with generalised epilepsy were enrolled in the generalised epilepsy part of the trial. They were randomly assigned to be prescribed lamotrigine or topiramate (both newer drugs) or valproic acid (the standard). Valproate and lamotrigine were about equally effective in preventing seizures in most patients, but in the subgroup of patients with idiopathic generalised epilepsy, valproate was significantly better. Valproate caused fewer side effects than topiramate.

The authors concluded that since valproate was more effective than lamotrigine and caused fewer side effects than topiramate, it should remain the standard first choice treatment for patients with generalised epilepsy.

What does this mean?
This doesn't mean that everybody with partial seizures should take lamotrigine and everybody with generalised seizures should take valproate. These are simply the recommended first try drugs for most newly-diagnosed patients. There are exceptions: both lamotrigine and valproate have significant drawbacks for women with epilepsy of childbearing age, as they are associated with causing higher rates of birth defects. For these patients, other drugs may suit them better.

It's also important to note that two new drugs, levetiracetam and zonisamide, which are now available in the UK, were licensed too recently to be included in this trial. We still need comparison data about these.

The study (published in two parts: partial epilepsy and generalised epilepsy ) and a commentary article were published in the March edition of The Lancet.

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