WEST PALM BEACH, Fla., Feb. 5 (UPI) -- In a head-to-head comparison, the newer anti-epileptic drug levetiracetam -- marketed as Keppra -- proved it was the equal of an established older medication in keeping patients seizure-free for at least a year, researchers said Monday.
"This study is the first to clearly demonstrate that levetiracetam is as effective as an older, commonly prescribed anti-seizure agent, carbamazepine, when used as monotherapy -- the sole drug therapy without the addition of other antiepileptic medication," said Steven Pacia, chief of the division of neurology and director of the Lenox Hill Hospital Comprehensive Epilepsy Center in New York, who did not participate in the study.
"Because patients with seizures differ in their tolerance to the side effects of antiepileptic medications, it is important for neurologists to have alternatives to offer their patients," Pacia told United Press International. "Levetiracetam is an effective and usually well-tolerated anti-epileptic medication that is gaining popularity with physicians who treat patients with seizure disorders."
Scottish researchers who conducted the study agreed.
"Selecting the most appropriate anti-epileptic drug for a patient with newly diagnosed epilepsy remains a significant challenge," said Martin Brodie, professor of medicine and clinical pharmacology at the Western Infirmary at the University of Glasgow in Scotland. "Although some of the newer agents may show better tolerability than anti-epileptic drugs, no comparative study has demonstrated improved efficacy for any of these over carbamazepine, phenytoin, or valproic acid."
In the study, to be published Tuesday in Neurology, the scientific journal of the Minneapolis-based American Academy of Neurology, Brodie and colleagues in Europe and South Africa enrolled 288 patients to receive Keppra and 291 patients to receive controlled-release carbamazepine. All the patients in the studies had at least two seizures in the previous 12 months.
Brodie said that doctors were allowed to change dosing of either drug to reduce side effects and improve tolerability as well as to control seizures to mimic how patients are treated in a clinical setting. He noted that other studies have had rigid dosing schedules or may have compared one drug with less-than-optimal available treatments.
For example, in some studies, newer drugs have been compared with carbamazepine -- but not in the controlled-release formulation -- giving the comparator drug a heightened advantage in having fewer side effects.
However, Brodie noted that his study "is the first study to comply with European regulations for the evaluation of new anti-epilepsy drugs" using optimized dosages and a clinically relevant endpoint.
At a recent meeting of North American epilepsy organizations, Gregory Barkley, clinical vice chairman of the department of neurology at Henry Ford Health System in Detroit, told United Press International that, to be meaningful for patients, seizures have to be halted for at least six months to a year.
"Patients need to be seizure-free for that length of time to be able to get a license to drive a car" in many states, Barkley said, noting he did not participate in the new study. Just reducing seizures to a few per week or per month is not sufficient, he said.
Brodie reported that about 73 percent of the patients in both the Keppra and carbamazepine groups were seizure-free for six months and about 57 percent of Keppra patients and about 59 percent of the carbamazepine patients were seizure-free for a year. Those differences were not statistically significant.
"The selection of treatment for a patient with newly diagnosed epilepsy must take side effects and long-term safety into consideration," Brodie reported. "More carbamazepine-treated patients discontinued treatment because of adverse events -- about 19.2 percent versus 14.4 percent, although this difference was not significant.
"Patients taking levetiracetam were more likely to report depression and insomnia, whereas those assigned to carbamazepine reported back pain more often," he said.
"The fast and sustained efficacy and good tolerability of levetiracetam in adults and children with partial-onset seizures, together with its favorable pharmacokinetic profile, lack of enzyme-inducing properties, and low potential for pharmacokinetic interactions, make it a promising anti-epileptic drug for use as initial monotherapy in newly diagnosed epilepsy," Brodie said.
"Compared with many other seizure medications on the market," Pacia said, "levetiracetam offers advantages that include infrequent allergies, few drug interactions, a broad spectrum of action and no reported adverse liver or bone marrow effects."
The study was sponsored by UCB of Brussels, Belgium. The company was involved in the design and conduct of the study; collection, management and analysis of the data; and preparation and review of the manuscript. All the authors of the study received honoraria from UCB.
