Pauline Anderson

December 12, 2013

WASHINGTON, DC — Researchers are making headway in determining how and when to withdraw antiepileptic drugs (AEDs) following resective surgery in patients with intractable temporal lobe epilepsy.

One new study suggests there is no difference in long-term seizure freedom in patients whose AED therapy was reduced or discontinued and those whose therapy was unchanged.

"Taking everything into account, the conclusion is that the results are the same whether you withdraw at 1 or 2 years, so if you think you're protecting patients by waiting longer, you're not," said study author, Lara Jehi, MD, research director, Epilepsy Program, Cleveland Clinic, Ohio.

This study was presented here at the American Epilepsy Society (AES) 67th Annual Meeting.

"Startling" Variability

Although the aim of epilepsy surgery is seizure freedom and use of as few AEDs as possible, there are no practice guidelines related to medication withdrawal.

"There is no standard of care when it comes to this topic," Dr. Jehi told Medscape Medical News. "There are absolutely no guidelines and no data to say when you should start reducing medications and how fast you should reduce medications."

What she finds "startling" is the amount of variability across centers and physicians as to how they deal with this issue, she said.

"Everyone knows seizures come back after surgery; the question is, are they coming back just because we withdraw the medication or were they going to come back any way," said Dr. Jehi.

Physicians typically start withdrawing medication 1 to 2 years after attaining seizure freedom. "This is a personal decision on the part of the physician and the patient, and it depends mainly on side effects the patient experiences, and this is especially true for pediatric patients where there may be cognitive concerns associated with continuing medications," noted Ruta Yardi, MD, also from the Cleveland Clinic.

Dr. Yardi was lead author of the new study, which included 609 patients who had undergone temporal lobe epilepsy surgery at the Cleveland Clinic between 1996 and 2011 and had between 6 months and 16.7 years of follow-up. The majority (86%) were adults.

Most of the patients (64%) had mesial temporal sclerosis, 17% had malformations of cortical development, 13% had tumors, 3% had vascular malformations, and 3% had other abnormalities.

The number of AEDs at the time of surgery ranged from 1 to 5, with a mean of 1.95. At last follow-up, the number of AEDs ranged from 0 to 5, with a mean of 1.42.

Also at the last follow-up, 38% of the patients had had no change in their baseline AEDs, while 62% had stopped (21%) or reduced (42%) their AEDs at some point. Continuing or withdrawing medications was independent of the side of resection, MRI findings, baseline seizure frequency, and the presence or absence of convulsions.

About 55% of the patients had a seizure recurrence at some point. Only higher baseline seizure frequency and history of generalization predicted seizure recurrence.

Of the group that had a seizure after reducing their medication and were put back on medication, more than two thirds regained their seizure freedom, said Dr. Yardi.

In those who underwent AED withdrawal, the mean timing of the earliest AED change was shorter in patients with recurrent seizures (1.04 years) than in those who were seizure free (1.44 years; P = .03).

No Long-Term Difference

However, there was no difference in the long-term rates of seizure freedom between those with AED withdrawal and those whose AEDs were not changed. For example, at almost 10 years after surgery, the rates of seizure freedom for both groups were about 40%.

An analysis that controlled for potential contributing factors found that staying on medication for 2 years compared with just 1 year did not offer any additional protection.

Dr. Yardi added that it's "reasonable" for patients to withdraw from medications a year after surgery, if they're informed that they have about a 10% risk for a breakthrough seizure. But this breakthrough seizure can be controlled by just reinstituting their previous AED dose, she said.

Today, fear of breakthrough seizures after medications are tapered is likely preventing some physicians from making medication changes, noted Dr. Yardi.

Researchers are working to find biomarkers that could more reliably predict seizure outcome in those withdrawing from AEDs, she said.

Patients often have strong feelings about staying on their AEDs or coming off them, added Dr. Jehi. A main concern is being able to drive; if patients have a seizure, they can't drive for 6 months or a year depending on where they live. Conversely, parents often want their children to come off their medications, she said.

American Epilepsy Society (AES) 67th Annual Meeting. Platform B.08. Presented December 9, 2013.


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