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Monday, January 13, 2014

After Surgery, Should All Epilepsy Patients Take Medications Indefinitely to Reduce Seizure Risk?



Should all patients continue to take antiepileptic drugs (AEDs) after surgery to reduce their risk for seizures? That was the question underlying a new large retrospective study from investigators at the Cleveland Clinic, presented here in December at the annual meeting of the American Epilepsy Society meeting in Washington, DC.

Neurology fellow, Ruta Yardi, MD, and her mentor, Lara Jehi, MD, director of the Cleveland Clinic’s outcomes research program, who designed the study and carried out the analysis, said their findings suggest that the answer to that question is “no.”

In designing the current study, said Dr. Jehi, “we really needed to know whether the seizures post-surgery were occurring because medication was withdrawn or reduced, or whether patients would have had them anyway, even if they continued on their same medications.”

Candidates for surgical resection have failed two or more AEDs and continue to have seizures, she explained. The goal of the surgery is freedom from seizures but neurologists have always taken precautions and kept their patients on their baseline dose for a year or two, and often longer. The investigators wanted to know more about what happens with medications over time — and whether seizures return once medication is lowered or stopped.



Dr. Yardi and colleagues reviewed medical records of 609 patients who had surgery between 1996 and 2011 and had detailed information on their medications before and after surgery and a history of their pre-and-post surgical seizures. About 20 percent of the patients had stopped their medication altogether. They also had a group of patients whose medications were not changed, which allowed the research team to answer questions that could help resolve the controversy about how much medication to use and for how long. Other retrospective studies did not have a defined control group of patients who remained on their pre-surgical medications, so were limited in their ability to draw reasonable comparisons.

The investigators reported that withdrawing AEDs increased the risk of breakthrough seizures during the first few months — 40 percent of them had breakthrough seizures. But more than two-thirds of these patients who were put back on their pre-surgical doses did not have further seizures.

That 60 percent of the patients whose medication was lowered or stopped did not have breakthrough seizures raises the question of whether everyone benefits from the addition of medication, said Dr. Jehi. “Every patient who has been seizure free deserves a chance to know whether they need to continue taking medications,” she said.

The investigators looked at the frequency of seizures during the first and second year post-surgery and found that those who remained on medicines for another year did not have any more protection than those whose medications were reduced or stopped a year after surgery. They reviewed data at four, six, and ten years. After a decade, approximately 50 percent of the patients in both groups were seizure free.

The number of AEDs at the time of surgery averaged two per patient. By the last follow-up, patients were taking on average 1.5 medications. By the last follow-up, 38 percent of the patients had no change in their baseline AEDs; 42 percent had reduced doses and 21 percent were no longer taking antiepileptic medicines. The differences in the management of the medication were not correlated to the side of resection, the MRI findings, the baseline seizure frequency, or the presence or absence of convulsions.

The only obvious predictor of seizure recurrence was a higher baseline seizure frequency. There was a higher rate of recurrence in patients who were withdrawn early, within the first six months compared to others whose medications were changed after the first year.

“The results of this large retrospective controlled study need to be further evaluated in a well-designed prospective randomized trial,” the neurologists said.

They said that they would explain these results to patients and say that more work is needed but that it is safer to remain on their baseline dose for a year and then their neurologist can start reducing their medications. “There will be a ten percent risk for a breakthrough seizure,” Dr. Jehi explained. “But if we don’t try to withdraw patients we will never know. And our findings suggest that half of them will be able to come off medicines altogether. We just don’t know who those patients will be, and we currently have no reliable tools to identify them confidently.”

“I don’t think we can assure patients taking two or three medicines that this practice will protect them from seizures,” Dr. Jehi added. “These medicines have side effects. Many physicians are afraid to wean their post-surgical patients off medicines, but maybe medication withdrawal is not as scary as we have assumed.”

The ultimate goal, the Cleveland Clinic neurologists said, is to identify biomarkers to identify those patients who can successfully stop or reduce their medications after surgery. And then they want to figure out the best time to do so.

They are also hoping that results from a prospective study can lead to guidelines that the field can follow. “The problem right now is that everyone has an opinion and no one has facts on which to base their opinion.”

That the medications were shown to work in these previously treatment refractory patients also suggest that the surgery may have made their brains pharmacologically more responsive to medicines. 

          See the extended expert discussion on these findings and what they may mean for epilepsy patients in the Dec. 19 issue of Neurology Today. See our archives for more research on epilepsy surgery: