Older epilepsy drugs do not prevent first seizure from brain tumors

Many physicians prescribe antiepileptic medications to patients with brain tumors, even to those with no seizure history. Now, a new review of studies casts doubt on the wisdom of using these drugs — which can carry serious side effects — to prevent a first seizure in these patients.

“There has always been a question about whether it is worth using antiepileptic medications to protect against seizures in patients with a brain tumor even though we can’t predict who will actually have a seizure,” said lead review author Ivo Tremont-Lukats, M.D.

Tremont-Lukats is staff neurologist at the Culicchia Neurological Clinic in New Orleans and a clinical assistant professor of neurology at Louisiana State University.

The review appears in the latest issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

The review included five studies looking at outcomes in 404 patients with brain tumors but no previous history of seizures. Some received one of three common antiseizure drugs: phenytoin (Dilantin), phenobarbital or divalproex sodium (Depakote). Others patients received a placebo or underwent close observation. Researchers found no differences in preventing the first seizure among the three groups.

“The results are such that we really can’t recommend seizure prevention using these three older anticonvulsants,” Tremont-Lukats said. “There was not a protective effect seen when using these drugs.”

In addition, the risk of side effects — such as drowsiness, bruising and unusual bleeding — was much higher for those using the drugs.

This review looked only at older medications. Because of a lack of usable studies, the researchers could not assess if newer antiepileptic medications might be more useful in stopping first seizures.

“We need to look at the newer generation of anticonvulsants to see if they can protect against first seizures,” Tremont-Lukats said. “These drugs are more specific and have fewer side effects, but we still do not know scientifically if they have a protective effect.”

Tremont-Lukats stressed that this recommendation is only for those who do not have a history of having seizures. If someone has a seizure, then antiepileptic drugs are indicated.

“If a physician wants to put a patient on these medications for more than seven days after surgery, then there may be a problem that the patient should bring up with their doctor,” says Tremont-Lukats. “After a week, there is no evidence that they help and ample evidence of side effects.”

Omkar Markand, M.D., director of the Comprehensive Epilepsy Program at the Indiana University School of Medicine, said that automatically placing people with brain tumors on antiepileptic medications is a common occurrence despite there being no scientific proof that it is useful.

“There is good evidence that all three of the medications have side effects that need to be weighed against any possible benefits,” Markand said. “For those medications, the side effects are worse than any possible benefit. This research is another indication that patients should probably ask their neurosurgeon or other physician if it is really necessary to place them on antiepileptic medication prior to experiencing a seizure.”

Markand stressed that recommendations based on this review are only applicable to the older medications phenytoin, phenobarbital and divalproex sodium.

“The take-home message is that the patients should not accept an automatic placement on antiepileptic medications,” Markand said. “They should ask questions about why these drugs are being prescribed. The needs of the individual should be determined instead of putting everyone on antiepileptic medications.”

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The Cochrane Collaboration is an international nonprofit, independent organization that produces and disseminates systematic reviews of health care interventions and promotes the search for evidence in the form of clinical trials and other studies of interventions. Visit cochrane.org for more information.

Tremont-Lukats IW, et al. Antiepileptic drugs for preventing seizures in people with brain tumors (Review). Cochrane Database of Systemic Reviews. 2008. Issue 2.

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