Levodopa and the Progression of Parkinson's Disease

• Published in: The New England journal of medicine Vol. 351; no. 24; pp. 2498 - 2508
• Main Authors: Fahn, Stanley, Oakes, David, Shoulson, Ira, Kieburtz, Karl, Rudolph, Alice, Lang, Anthony, Olanow, C Warren, Tanner, Caroline, Marek, Kenneth
• Format: Journal Article
• Language: English
• Published: Boston, MA Massachusetts Medical Society 09.12.2004
• Subjects: Aged; Antiparkinson Agents - administration & dosage; Antiparkinson Agents - therapeutic use; Biological and medical sciences; Carbidopa - administration & dosage; Carbidopa - therapeutic use; Clinical trials; Corpus Striatum - diagnostic imaging; Corpus Striatum - metabolism; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Progression; Dopamine; Dopamine Plasma Membrane Transport Proteins; Double-Blind Method; Drug Combinations; Drug dosages; Female; General aspects; Humans; Levodopa - administration & dosage; Levodopa - therapeutic use; Male; Medical sciences; Membrane Glycoproteins - metabolism; Membrane Transport Proteins - metabolism; Middle Aged; Nerve Tissue Proteins - metabolism; Neurology; Oxidative stress; Parkinson Disease - diagnostic imaging; Parkinson Disease - drug therapy; Parkinson Disease - metabolism; Parkinson's disease; Tomography, Emission-Computed, Single-Photon; Agonist; Nervous system diseases; Prognosis; Parkinson disease; Antiparkinson agent; Cerebral disorder; Medicine; D2 Dopamine receptor; Central nervous system disease; Evolution; Degenerative disease; Levodopa; Extrapyramidal syndrome
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMoa033447

This randomized trial examined the effect of levodopa on the progression of Parkinson's disease. After 40 weeks of treatment followed by another 2 weeks for washout, the clinical severity of Parkinson's disease was greater in patients receiving placebo than in those treated with levodopa. However, neuroimaging data suggested a greater loss of dopamine nerve terminals in the patients treated with levodopa. In this randomized trial the clinical data indicate that levodopa reduces symptoms without accelerating clinical progression of Parkinson's disease. However, the neuroimaging data are not concordant. Parkinson's disease is a progressively disabling neurodegenerative disorder that is manifested clinically by bradykinesia, tremor, rigidity, flexed posture, postural instability, and freezing of gait. It is characterized pathologically by the loss of pigmented dopaminergic neurons in the substantia nigra. The course of the clinical decline parallels that of the progressive degeneration of the remaining dopaminergic neurons. 1 The use of levodopa as dopamine-replacement therapy is highly effective in ameliorating the symptoms of the disease and remains the standard drug with which other therapies are compared. 2 , 3 Because levodopa and dopamine can generate reactive oxygen species and induce the degeneration of cultured . . .