Clinical

Lamotrigine and valproate: drugs of choice for newly diagnosed epilepsy

Last Updated: 2007-03-22 18:46:02 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Results of two concurrent, randomized controlled trials comparing Standard and New Antiepileptic Drugs (SANAD) suggest that in the absence of mitigating circumstances, lamotrigine should be considered the first-choice treatment for patients newly diagnosed with partial epilepsy. For patients with generalized and unclassifiable epilepsy, valproate appears to be better as the initial medication.

The British research team, led by Dr. Anthony G. Marson from the University of Liverpool, notes that carbamazepine is considered the drug of first choice for partial epilepsy. Many new anti-epileptics have come to market, but because trials were short and often failed to address quality of life issues and costs, there is no consensus regarding which drugs are better.

Between 1999 and 2004, the SANAD study recruited 1721 patients older than age 4 with partial onset seizures, who were randomized to carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate. Follow-up lasted until 2006.

As the authors note in their report, published in the March 24th issue of The Lancet, treatment was not blinded. The treating clinicians determined dosage and rate of titration.

The researchers found that gabapentin and topiramate were the poorest performing drugs. Oxcarbazepine was included in 2001, so the trial was not powered to fully assess this drug. Therefore, the final analysis was between lamotrigine and carbamazepine.

Lamotrigine was significantly better than carbamazepine for time to treatment failure and was better tolerated. Lamotrigine was also more cost-effective than carbamazepine in cost per seizure avoided and cost per quality-adjusted life year (QALY) gained.

Dr. Marson and his associates note that some situations -- such as risk of teratogenicity, bone health, and drug interactions - may affect treatment decisions. Otherwise, lamotrigine appears to be the best first choice treatment for patients with partial epilepsy.

In the second portion of the SANAD trial, Dr. Marson's group recruited 716 patients with generalized onset seizures or seizures that were difficult to classify. The drug of first choice for these patients has been valproate. The patients were randomized to valproate, lamotrigine, or topiramate.

Although valproate had the lowest cost per seizure avoided, topiramate had the lowest cost per QALY. Still, "valproate is better tolerated than topiramate and more efficacious than lamotrigine," the authors note, "and should remain the drug of first choice for many patients with generalized and unclassified epilepsies."

Dr. Marson and his associates caution, however, that valproate may cause fetal malformations, so other treatment should probably be considered for women of childbearing age.

In a related editorial, Dr. Jacqueline A. French, of the University of Pennsylvania in Philadelphia, lauds the SANAD trial for overcoming many limitations of previous trials and providing data for some of the new anti-epileptic drugs.

She also comments that selecting drug therapy to treat epilepsy is "not completely cut and dried," partly because of the many variables that trials like SANAD cannot control.

Dr. French emphasizes that by designating one drug as first choice, physicians may fail to consider individual patients' needs and characteristics. For example, lamotrigine can cause insomnia so it might not be a good choice for patients who have sleep disorders. It is also cleared much more quickly during pregnancy, she adds.

On the other hand, in valproate is more likely to cause weight gain and is associated with life-threatening pancreatitis. It is also known to alter liver function tests and platelet counts, in addition to its potential teratogenicity.

"Simple is good, but overly simplistic may not provide the optimum benefit to our patients," Dr. French concludes.

Lancet 2007;369:970-972,1000-1026.