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Levodopa-induced Dyskinesias Relieved With Anti-epileptics : Presented at AAN

By Ed Susman

SAN FRANCISCO, CA -- April 30, 2004 -- Subjects with Parkinson's disease who have levodopa-induced dyskinesias may obtain relief by adding dosages of the anti-epileptic agent levetiracetam, according to results of a recent pilot study.

"Although we only had a few patients in this study, the results we saw are promising enough for us to plan a Phase-II trial that may give patients a therapeutic option when their dyskinesias become troublesome," said Theresa Zesiewicz, MD, Associate Professor of Neurology, Parkinson's Disease and Movement Disorders Center, University of South Florida, Tampa, United States.

Dr. Zesiewicz recruited 9 patients with Parkinson's Disease for the pilot study, all of whom were suffering from troublesome movement disorders associated with long-term treatment with levodopa, the drug commonly used by patients with the disorder. "After 10 or 15 years, most patients on levodopa developed these dyskinesias," Dr. Zesiewicz said at her poster presentation at the 56^th annual meeting of the American Academy of Neurology. Reduction of the dose of levodopa to reduce the unwanted and debilitating movements may result in increased Parkinsonian tremors.

In the study, patients who were able to tolerate levetiracetam had marked improvements in dyskinesia. "Our study showed levetiracetam reduced dyskinesia and, importantly, did not interfere with the efficacy of levodopa in controlling Parkinson's disease symptoms," Dr. Zesiewicz said.

Five of the 9 patients dropped out of the study, however, because the use of levetiracetam caused somnolence in 3 patients, obtundation in another and dizziness in a third. Dr. Zesiewicz noted that while levetiracetam itself causes somnolence, so does levodopa, and so does Parkinson's disease.

"We believe that we started these patients at too high a dose of levetiracetam," Dr. Zesiewicz noted. "In the Phase-II study we are planning, we would use the liquid form of levetiracetam, and start patients at 25 mg, and slowly titrate them upwards as their tolerance for the drug and symptoms warranted."

The pilot study was not funded by UCB Pharma, the maker of levetiracetam, but the company did supply the drug for the patients. Dr. Zesiewicz said she would be seeking funding from UCB Pharma for an expanded Phase-II clinical trial.

Dr. Zesiewicz said she currently uses levetiracetam in patients who are having difficulty with troublesome levodopa-associated dyskinesia. Animal studies, she said, support the use of levetiracetam in these patients, which is why she attempted their use in the pilot study. She said that, as far as she knows, her study was the first to use anti-epileptics in levodopa-induced dyskinesia.

In the study, patients who were able to maintain levetiracetam treatment for 60 days showed an improvement in "on" time -- the period when levodopa treatment is effective -- from 43% at baseline to 61% at the end of the study. That difference, even with the small numbers of patients, still achieved statistical significance at the P = .02 level, Dr. Zesiewicz noted.


[Presentation title: "Levetiracetam (Keppra) in the Treatment of Levodopa-Induced Dyskinesia in Parkinson's Disease." Abstract #P06.138.]

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