Best First-Choice Drugs for Epilepsy ID'd

But Patient Differences Complicate Effort to Simplify Epilepsy Drug Choice

Medically Reviewed by Louise Chang, MD on March 22, 2007
From the WebMD Archives

March 22, 2007 - Lamictal is the best first-choice drug for partial epilepsy, while valproic acid is the best first choice for generalized epilepsy, two major clinical trials show.

But for patients who learn they have epilepsy, finding the right drug to control their seizures will continue to be a complicated process. That's because each epilepsy drug has different benefits and different risks for different people.

The clinical trials offer lots of new information, notes neurologist Anthony G. Marson, MD, of the University of Liverpool, England, the leader of the Standard and New Antiepileptic Drugs (SANAD) studies.

"What these trials do is give you reliable data about the likelihood of a drug's success relative to seizure control," Marson tells WebMD. "So now we can talk to patients about the relative benefits they can expect when weighing the hazards of these drugs."

Epilepsy Drug Choice Simplified

As their names imply, the trials compared standard epilepsy treatments to a wide range of newer drugs. The two trials looked at two different groups of patients.

Epilepsy comes in a multitude of forms, but experts agree on two basic types. In partial or focal epilepsy, mixed-up electrical signals start in one area of the brain and spread out, causing a seizure. In generalized epilepsy, seizures result from a surge of electrical activity all across the brain.

The first trial looked at 1,721 patients newly diagnosed with partial epilepsy. It compared an older drug, carbamazepine (a common brand name is Tegretol) to gabapentin (Gabarone, Neurontin), Lamictal, Trileptal, and Topamax.

"[Lamictal] seems to be the winner," Marson says.

The second trial looked at 716 patients newly diagnosed with generalized epilepsy. It compared the older drug valproic acid (in the U.S., Depakote is the most popular member of this drug family) to Lamictal and Topamax.

"Valproate [the British term for valproic acid] is a much better drug at controlling generalized seizure than the others," Marson says.

But these drugs aren't necessarily the best first-choice treatment for all patients, argues Jacqueline French, MD, head of Penn Epilepsy Center at the University of Pennsylvania, Philadelphia.

"This is making simple something that is not so simple," French tells WebMD.

French's editorial accompanies the Marson reports in the March 24 issue of The Lancet.

Epilepsy Drug Choice Still Complex

Marson's study looked at how well the epilepsy drugs control seizures, their general tolerability, and their cost.

Those are important things, French says. But other things are equally important, such as the likelihood a drug will cause a serious health risk or a drug's interactions with other medications.

For example, some epilepsy drugs make oral contraceptives less effective. And oral contraceptives, French says, make Lamictal less effective.

"Patients with epilepsy should think about the things that are important for them," French advises. "Say I want to get pregnant in the next five years. Or I am very nervous about side effects that might seriously compromise my health. Or I need protection against seizures from day one, which Lamictal is not going to do."

Marson agrees that the SANAD studies don't answer all these questions. But the studies do offer important new information to guide patient choices.

The most important choice patients make, French says, is their choice of doctor.

"A person should definitely ask, 'What kind of epilepsy do I have?' And if a doctor can't answer that question, it is time to find another doctor. Because not everybody should be treating epilepsy," French says.

French says that about half of patients get excellent seizure control with any of the available epilepsy drugs. The problem, she and Marson agree, is that nobody can predict which patients will respond to treatment and which are among the 30% of patients for whom none of the drugs offers sufficient seizure control.

"There are some new drugs in the pipeline. We hope one will make a big impact," French says. "But over the last decade and a half we thought we were incredibly successful by making 10 new drugs available. And yet we have not even made a dent in the number of treatment-resistant patients. That is enormously frustrating. But we'll keep trying."

That's important for far more people than is generally appreciated.

"Nobody realizes how prevalent this problem is because it is so poorly accepted by the community at large," French says. "Patients try as hard as they can to keep anybody from knowing. They keep it hidden."

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SOURCES: Marson, A.G. The Lancet, March 24, 2007; vol 369: pp 1000-1015 and 1016-1026. French, J.A. The Lancet, March 24, 2007; vol 369: pp 970-971. Anthony Marson, MD, reader and consultant neurologist, University of Liverpool, U.K. Jacqueline French, MD, professor of neurology and director, Penn Epilepsy Center, University of Pennsylvania, Philadelphia.

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