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New Study Suggests Levetiracetam May Benefit Patients with Parkinson’s Disease

SAN FRANCISCO, April 29 /PRNewswire/ -- In patients with Parkinson's disease, the antiepileptic drug levetiracetam (Keppra®) reduced the involuntary movements (dyskinesia) associated with levodopa, the medication most commonly used to treat Parkinson's disease, according to a study presented today at the 56th annual meeting of the American Academy of Neurology.(1) The independent study is one of the first to specifically evaluate an antiepileptic drug for the treatment of levodopa-induced dyskinesia in Parkinson's patients.

"Levodopa-induced dyskinesia remains one of the biggest challenges in treating Parkinson's disease because it is a common side effect and is difficult to manage," said lead investigator Theresa Zesiewicz, M.D., assistant director of the Parkinson's Disease and Movement Disorders Center, and associate professor of neurology at the University of South Florida. She explained that levodopa can effectively control Parkinson's disease symptoms -- stiffness, slow movement and tremors -- but after five to eight years, it often causes the side effect of dyskinesia. "Our study showed levetiracetam reduced dyskinesia and, importantly, did not interfere with the efficacy of levodopa in controlling Parkinson's disease symptoms," she said. An anticonvulsant with a novel mechanism of action, levetiracetam is currently approved by the U.S. Food and Drug Administration for the adjunctive treatment of partial-onset seizures in adults.

Study and Findings

The prospective, open-label pilot study included nine Parkinson's disease patients (three women and six men, average age 65 years) being treated with levodopa and who were experiencing peak-dose dyskinesia for at least 25 percent of their waking hours. Two patients dropped out before completing their diaries, leaving seven patients for the efficacy analysis. Ten days of treatment with levetiracetam resulted in changes suggesting improvement in levodopa-induced dyskinesia. Further analysis after 60 days of treatment with levetiracetam yielded the following results:

* A significant increase in "ON" time without dyskinesia or with non- troublesome dyskinesia by 42 percent, from 43 percent at baseline to 61 percent at 60 days (p = 0.02). ON time refers to the time when levodopa or other medications effectively treat the symptoms of Parkinson's disease. * A trend for decreased ON time with troublesome dyskinesia by 52 percent, from 23 percent at baseline to 11 percent at 60 days (p = 0.13) * No significant change in OFF time (31 percent at baseline vs. 27 percent at 60 days). OFF time occurs when Parkinson's disease medications no longer control the disease symptoms, resulting in slowness, stiffness and immobility. * Improved the clinical global impression (CGI) of dyskinesia in six patients (improvement was marked in one, moderate in two and minimal in three), and one reported no change or worsening in dyskinesia.

There were no significant changes in other standard measures, including the Abnormal Involuntary Movement Scale (AIMS) and the Unified Parkinson's Disease Rating Scale (UPDRS).

In the study, levetiracetam was administered at a starting dose of 250 mg/day and escalated up to as much as 3000 mg over a 60-day period. The investigators evaluated the patients at baseline and every 10 days thereafter, assessing the amount of ON time with no dyskinesia, with non-troublesome dyskinesia, and with troublesome dyskinesia; OFF time; and CGI, AIMS and UPDRS scores.

Of the nine patients who started the study, five withdrew due to side effects, the most frequent being increased somnolence (sleepiness), which occurred in three patients. One patient withdrew because of obtundation (dulled or reduced level of alertness or consciousness) and one due to dizziness and confusion.

"Many Parkinson's disease patients experience somnolence, either from the disease itself or from medications used to treat it -- so they may be more susceptible to somnolence from levetiracetam than are patients with epilepsy," said Dr. Zesiewicz. Because levetiracetam, nonetheless, appeared to be beneficial in reducing the dyskinesia, she recommended that "future studies in Parkinson's disease patients start with a lower dose and titrate more slowly."

About Parkinson's Disease

Parkinson's disease (PD) is a chronic and severely debilitating neurodegenerative disorder that affects more than two million people worldwide, and at least 750,000 people in the United States. PD is associated with bradykinesia (slowed movements), tremor, rigidity and postural instability. While PD most commonly affects people beginning in their 60s, it can occur as early as age 20, and as many as 10 percent of cases occur before age 40.(2)

PD is caused by degeneration of the substantia nigra (SN), a part of the brain involved in movement control. Cells in the SN interact with other movement control centers by secreting a neurotransmitter (a substance that transmits signals from nerve to nerve) known as dopamine. When these "dopaminergic" neurons in the SN die, the other centers become unregulated, resulting in most of the movement-related symptoms of PD.(2) Most PD medications either mimic the effect of dopamine, increase dopamine levels or extend the action of dopamine in the brain. Levodopa, commonly known as L- dopa, has been the traditional drug used for treatment, but it can cause side effects (e.g., spasmodic movements, called dyskinesia) and tends to become less effective over time.(3) Various brain surgical procedures are also used in severe cases of PD; research on other therapies, such as stem cell implantation, is underway.

References (1) Zesiewicz TA, Sullivan KL, Maldonado JL, Tatum WO, Hauser RA. Levetiracetam (Keppra) in the treatment of levodopa-induced dyskinesia in Parkinson's disease. Poster 138 presented at: 56th annual meeting of the American Academy of Neurology, April 24 - May 1, 2004, San Francisco, CA. (2) We Move. Parkinson's disease - frequently asked questions. http://www.wemove.org/par/par_faq.html. Accessed February 27, 2004. (3) MayoClinic.com. Parkinson's Disease. http://www.mayoclinic.com/invoke.cfm?id=DS00295. Accessed February 27, 2004.

Source: The University of South Florida

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