Joseph Jankovic, MD

Joseph Jankovic, MD

Levodopa or L-dopa – long an accepted treatment in Parkinson's disease – remains the gold standard, said an expert at Baylor College of Medicine (BCM).

Joseph Jankovic, MD, professor of neurology and director of the Parkinson's Disease Center and Movement Disorders Clinic at BCM, participated in the Early versus Later Levodopa (ELLDOPA) study published recently in the New England Journal of Medicine by the Parkinson's Study Group.

Jankovic said the study was the first thorough assessment of the effectiveness and toxicity of levodopa or L-dopa in treating patients with the disorder.

"L-dopa is clearly the most effective drug in the treatment of the symptoms of Parkinson's, but there are many unresolved questions about how the drug should be used in the management of patients with Parkinson's Disease," said Jankovic. "The ELLDOPA study clearly demonstrates that L-dopa is safe and does not cause toxicity."

The finding is important because some experts have had reservations about levodopa, he said.

"Because of the concern that levodopa may be toxic, some people have argued that it should be used only in advanced stages of the disease," said Jankovic, the principal investigator of BCM's portion of the study. "The other reason why in some patients levodopa should be used later in the course of the disease is because it is otherwise associated with side effects including abnormal involuntary muscle contractions and movements (dyskinesia) or a ‘wearing-off' effect,' in which the duration of benefits shortens with chronic use."

The nationwide study tracked the progress of 361 Parkinson's patients for 40 weeks. During that time, they received varying dosages of levodopa. The medication was then withdrawn, and patients were monitored for an additional two weeks.

Although some participants experienced side effects – the most common being nausea, jerky movements, and a decline in the drug's potency over time –L-dopa's benefits appeared to outnumber its drawbacks.

Concerns over levodopa's effect on nerve cells that produce dopamine have in the past raised questions over how it should be administered -- if at all, said Jankovic. Some medical experts have speculated that levodopa causes these nerve cells to degenerate over time.
Although the long-term effects of the drug are still not completely understood, clinical data from the ELLDOPA study indicate that levodopa clearly suppresses the symptoms of Parkinson's disease and may even slow down its progression.

"If L-dopa were toxic, we would expect that those patients who were treated with a higher dose to have a more severe form of the disease after the withdrawal of the drug, but that did not turn out to be the case," Jankovic said.

Levodopa, designed to replenish dwindling supplies of dopamine in the brain, has been used since the 1960's primarily as a treatment for Parkinson's and less commonly in other neurological disorders. Until the ELLDOPA study, a thorough analysis of the drug's effects had never been conducted.

"What is amazing is that levodopa has been around for a long time, but there are still unresolved issues about it," said Jankovic. "There have been other studies that have had all kinds of pathological flaws, but this is the first really well-designed study."

Jankovic recommends that younger Parkinson's patients who will require levodopa for long periods of time hold off using it and instead initially try alternative treatments such as dopamine agonists, which stimulate brain's dopamine receptors and cause the brain to "think" it is receiving dopamine.

"When the symptoms, such as tremor, slowness of movement, stiffness of muscles and problems with gait and balance begin to cause disability, levodopa should be administered," said Jankovic.

Approximately 30 institutions participated in the nationwide study.

The citation for the article to which Jankovic refers is N Engl J Med 2004; 351:2498-2508, Dec 9, 2004.

Funding for this study came from grants from the National Institute of Neurological Disorders and Stroke, the U.S. Department of Defense and the General Clinical Research Center of the National Center for Research Resources of the National Institutes of Health. Teva Pharmaceuticals of Israel provided the carbidopa-levodopa and matching placebo tablets.