New Study Suggests Levodopa May Slow Parkinson's Disease
Levodopa is the most powerful drug available to treat the symptoms of Parkinson disease, and almost all patients with the disease will
eventually need to take it.
But there has long been controversy about when it should be started, in part because of concern that the medicine itself might cause further
damage to the brain cells that are impaired in this disease.
To resolve the controversy, a Columbia University scientist led a team of experts from the Parkinson Study Group to study levodopa's effect on
the rate of progression of the disease.
The study, reported in the December 9 issue of The New England Journal of Medicine, showed not only that levodopa does not appear to worsen
the disease, but that it may actually slow its progression.
A total of 38 Parkinson Study Group sites across the U.S. and Canada conducted this multi-center, placebo-controlled, double-blind clinical
trial involving 361 newly diagnosed Parkinson disease patients.
Stanley Fahn, M.D., professor of neurology at Columbia University Medical Center, was the principal investigator of the study. Although there
is still uncertainty on how to interpret the study and further investigation will be necessary to prove levodopa's value beyond reasonable doubt,
we found that levodopa did not accelerate the pace of Parkinson disease, said Dr. Fahn. Now patients can feel more secure about the drug and may
wish to start it sooner rather than later.
The co-principal investigator, Ira Shoulson, M.D., professor of neurology at the University of Rochester, added, The results of this study are
important because they help provide confidence for both patients with Parkinson disease and their doctors about the safety of levodopa. Drs. Fahn
and Shoulson advised, however, The results do not prove that levodopa slows the underlying nerve degeneration of Parkinson disease, and a
differently designed clinical study will be necessary to address this concept.
A follow-up study is already in the planning stages. Drs. Fahn and Shoulson further cautioned, The high dose required for the best effect
produced more undesirable side effects, such as abnormal involuntary movements, which is another reason patients have delayed starting
Parkinson's disease is a progressive neurological disorder that affects approximately 1.5 million Americans. The disease is characterized by
tremor, stiffness, slowness and eventually poor balance control. The symptoms are due to loss of nerve cells in the brain that contain
The most effective treatment for Parkinson's is dopamine replacement therapy with the drug levodopa, which is changed to dopamine in the
brain. Levodopa is commonly sold in combination with carbidopa under the brand name Sinemet or its generic equivalent. Over time, Parkinson
disease continues to worsen, and new symptoms emerge that do not respond as favorably to levodopa therapy. Because Parkinson's is a progressive
disorder, the symptoms worsen with time.
Research physicians at Columbia University Medical Center and 37 other Parkinson Study Group sites in the United States and Canada evaluated
361 newly diagnosed participants with early Parkinson disease. There were four treatment groups: (1) carbidopa/levodopa 12.5/50 mg three times
daily; (2) carbidopa/levodopa 25/100 mg three times daily; (3) carbidopa/levodopa 50/200 mg three times daily; and (4) matching placebo. Neither
the study participants nor the investigators were aware of the treatment assignments.
After 40 weeks (9 months) of treatment, the medications were withdrawn, and 2 weeks later, after allowing the symptomatic benefit of levodopa
to dissipate, the subjects were evaluated to see how far the disease had worsened since the baseline examination 42 weeks earlier. The
placebo-treated group represented the natural progression of the illness.
The primary outcome of the study was to measure Parkinson impairment between the beginning of the study (week zero) and the end of the study
(week 42). If levodopa accelerated disease progression, then those treated with levodopa would be expected to have more severe impairment than
the placebo-treated group after the symptomatic benefit of levodopa had been eliminated through the 2-week washout phase. If levodopa slowed
progression, then the levodopa-treated subjects would be expected to have less severe Parkinson disease than the placebo-treated group.
The clinical results showed a clear-cut benefit in favor of levodopa. Moreover, the higher the dosage, the more beneficial the result. A
question remains, however, as to whether the 2-week washout of the drug was sufficient to account for the elimination of all of levodopa's
The study also contained a brain imaging component that showed the opposite effect from the clinical research evaluations. Participants
underwent evaluation of their dopamine neurons at the beginning of the study and again after 40 weeks of treatment. These results suggest that
levodopa could possibly have accelerated the loss of dopamine neurons. These findings also raise the question as to whether levodopa treatment
interfered with the imaging by temporarily altering the chemistry of the dopamine neurons.
The PSG (www.Parkinson-Study-Group.org) is a non-profit, cooperative group of Parkinson
disease experts from medical centers in the United States and Canada who are dedicated to improving treatment for persons affected by Parkinson
The National Institutes of Health and the Department of Defense's Neurotoxin Project provided financial support for this study, known as the
ELLDOPA (Earlier versus Later LevoDOPA Therapy in Parkinson Disease) Study. Teva Pharmaceuticals Industries of Netanya, Israel, which markets
generic levodopa, provided the supply of levodopa and matching placebos gratis.
Columbia University Medical Center provides international leadership in basic, pre-clinical and clinical research, medical education, and
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and institutions. With a strong history of some of the most important discoveries in health care, its researchers are leading the development of
novel therapies and advances to address a wide range of health conditions.