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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Levodopa and the progression of parkinson’s disease
New England Journal of Medicine, Volume 351, No. 24, Year 2004
Notification
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Description
Background Despite the known benefit of levodopa in reducing the symptoms of Parkinson’s disease, concern has been expressed that its use might hasten neurodegeneration. This study assessed the effect of levodopa on the rate of progression of Parkinson’s disease. methods In this randomized, double-blind, placebo-controlled trial, we evaluated 361 patients with early Parkinson’s disease who were assigned to receive carbidopa-levodopa at a daily dose of 37.5 and 150 mg, 75 and 300 mg, or 150 and 600 mg, respectively, or a matching placebo for a period of 40 weeks, and then to undergo withdrawal of treatment for 2 weeks. The primary outcome was a change in scores on the Unified Parkinson’s Disease Rating Scale (UPDRS) between baseline and 42 weeks. Neuroimaging studies of 142 subjects were performed at baseline and at week 40 to assess striatal dopamine-transporter density with the use of iodine-123-labeled 2-β-carboxymethoxy-3-β-(4-iodophenyl)tropane ([123I] β-CIT) uptake. results The severity of parkinsonism increased more in the placebo group than in all the groups receiving levodopa: the mean difference between the total score on the UPDRS at baseline and at 42 weeks was 7.8 units in the placebo group, 1.9 units in the group receiving levodopa at a dose of 150 mg daily, 1.9 in those receiving 300 mg daily, and -1.4 in those receiving 600 mg daily (P<0.001). In contrast, in a substudy of 116 patients the mean percent decline in the [123I] β-CIT uptake was significantly greater with levodopa than placebo (-6 percent among those receiving levodopa at 150 mg daily,-4 percent in those receiving it at 300 mg daily, and-7.2 percent among those receiving it at 600 mg daily, as compared with-1.4 percent among those receiving placebo; 19 patients with no dopaminergic deficits on the baseline scans were excluded from the analysis) (P=0.036). The subjects receiving the highest dose of levodopa had significantly more dyskinesia, hypertonia, infection, headache, and nausea than those receiving placebo. conclusions The clinical data suggest that levodopa either slows the progression of Parkinson’s disease or has a prolonged effect on the symptoms of the disease. In contrast, the neuroimaging data suggest either that levodopa accelerates the loss of nigrostriatal dopamine nerve terminals or that its pharmacologic effects modify the dopamine transporter. The potential long-term effects of levodopa on Parkinson’s disease remain uncertain. © 2004 Massachusetts Medical Society. All rights reserved.
Authors & Co-Authors
Fahn, Stanley
United States, New York
Columbia University
Kieburtz, Karl D.
Unknown Affiliation
Lang, Anthony E.
Canada, Toronto
Toronto Western Hospital University of Toronto
Olanow, Charles Warren
United States, New York
Icahn School of Medicine at Mount Sinai
Tanner, Caroline M.
United States, Sunnyvale
Parkinson's Institute
Schifitto, Giovanni
United States, Rochester
University of Rochester
Goetz, Christopher G.
United States, Chicago
Rush University Medical Center
Ford, Blair
United States, New York
Columbia University
Jankovic, Joseph J.
United States, Houston
Baylor College of Medicine
Hunter, Christine B.
United States, Houston
Baylor College of Medicine
Friedman, Joseph Harold
United States, Providence
Brown University
Standaert, David G.
United States, Boston
Massachusetts General Hospital
Schwarzschild, Michael A.
United States, Boston
Massachusetts General Hospital
Gauthier, Serge G.
Canada, Verdun
Mcgill University Research Centre for Studies in Aging
Manyam, Bala V.
United States, Temple
Scott and White
Martin, W. R. Wayne
Canada, Edmonton
University of Alberta
Hauser, Robert A.
United States, Tampa
University of South Florida, Tampa
Perlmutter, Joel S.
United States, St. Louis
Washington University in St. Louis
Racette, Brad A.
United States, St. Louis
Washington University in St. Louis
Suchowersky, Oksana
Canada, Calgary
University of Calgary
Kurlan, Roger M.
United States, Rochester
University of Rochester
Adler, Charles H.
United States, Scottsdale
Mayo Clinic Scottsdale-phoenix, Arizona
Simuni, Tanya
United States, Philadelphia
University of Pennsylvania
Lyons, Kelly E.
United States, Coral Gables
University of Miami
Brin, Mitchell F.
United States, New York
Icahn School of Medicine at Mount Sinai
Pahwa, Rajesh
United States, Lawrence
University of Kansas
Wszołek, Zbigniew K.
United States, Jacksonville
Mayo Clinic in Jacksonville, Florida
Uitti, Ryan J.
United States, Jacksonville
Mayo Clinic in Jacksonville, Florida
Waters, Cheryl H.
United States, Los Angeles
University of Southern California
Kumar, Rajeev T.S.
United States, Englewood
Colorado Neurological Institute
Dawson, Ted M.
United States, Baltimore
Johns Hopkins University
Reich, Stephen G.
United States, Baltimore
Johns Hopkins University
Statistics
Citations: 1,523
Authors: 32
Affiliations: 35
Identifiers
Doi:
10.1056/NEJMoa033447
ISSN:
00284793
Research Areas
Disability
Study Design
Case-Control Study