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Comparison of therapeutic effects and mortality data of levodopa and levodopa combined with selegiline in patients with early, mild Parkinson's disease

^a Parkinson's Disease Research Group of the United Kingdom, National Hospital for Neurology and Neurosurgery, London WC1N 3BG

Abstract

Objective: To compare effectiveness of levodopa and levodopa combined with selegiline in treating early, mild Parkinson's disease.
Design: Open, long term, prospective randomised trial.
Setting: 93 hospitals throughout United Kingdom.
Subjects: 520 patients with early Parkinson's disease who were not receiving dopaminergic treatment.
Interventions: Treatment with levodopa and dopa decarboxylase inhibitor (arm 1) or levodopa and decarboxylase inhibitor in combination with selegiline (arm 2).
Main outcome measures: Assessments of serial disability, frequency and severity of adverse events, and deaths from all causes.
Results: After average of 5.6 years' follow up, mortality ratio in arm 2 compared with arm 1 was 1.57 (95% confidence interval 1.09 to 2.30), and difference in survival between the two arms was significant (log rank test, P=0.015). Hazard ratio adjusted for age and sex was 1.49 (1.02 to 2.16), and after adjustment for other baseline factors it increased to 1.57 (1.07 to 2.31). Patients in arm 1 had slightly worse disability scores than those in arm 2, but differences were not significant. Functionally disabling peak dose dyskinesias and on/off fluctuations were more frequent in arm 2 than arm 1. During the trial the dose of levodopa required to produce optimum motor control steadily increased in arm 1 (median daily dose 375 mg at 1 year and 625 mg at 4 years), but median dose in arm 2 did not change (375 mg).
Conclusions: Levodopa in combination with selegiline seemed to confer no clinical benefit over levodopa alone in treating early, mild Parkinson's disease. Moreover, mortality was significantly higher with combination treatment, casting doubts on its chronic use in Parkinson's disease.

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• Davie, C. A. (2008). A review of Parkinson's disease. Br Med Bull 86: 109-127 [Abstract] [Full text]  
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• Wheatley, K., Stowe, R. L, Clarke, C. E, Hills, R. K, Williams, A. C, Gray, R. (2002). Evaluating drug treatments for Parkinson's disease: how good are the trials?. BMJ 324: 1508-1511 [Full text]  
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• Miyasaki, J. M., Martin, W., Suchowersky, O., Weiner, W. J., Lang, A. E. (2002). Practice parameter: Initiation of treatment for Parkinson's disease: An evidence-based review: Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 58: 11-17 [Abstract] [Full text]  
• Guttman, M., Slaughter, P. M., Theriault, M.-E., DeBoer, D. P., Naylor, C. D. (2001). Parkinsonism in Ontario: Increased mortality compared with controls in a large cohort study. Neurology 57: 2278-2282 [Abstract] [Full text]  
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• Olanow, C. W., Watts, R. L., Koller, W. C. (2001). An algorithm (decision tree) for the management of Parkinson's disease (2001):: Treatment. Neurology 56: S1-S88 [Full text]  
• Langston, J. W., Tanner, C. M. (2000). Selegiline and Parkinson's disease: It's deja vu--again. Neurology 55: 1770-1771 [Full text]  
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• Münchau, A, Bhatia, K P (2000). Pharmacological treatment of Parkinson's disease. Postgrad. Med. J. 76: 602-610 [Full text]  
• Larner, A J, Farmer, S F (1999). Recent advances: Neurology. BMJ 319: 362-366 [Full text]  
• (1999). Developments in the treatment of Parkinson's disease. DTB 37: 36-40 [Abstract] [Full text]  
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• Lang, A. E., Lozano, A. M. (1998). Parkinson's Disease- Second of Two Parts. NEJM 339: 1130-1143 [Full text]  
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• Thorogood, M., Armstrong, B., Nichols, T., Hollowell, J. (1998). Mortality in people taking selegiline: observational study. BMJ 317: 252-254 [Abstract] [Full text]  
• Ben-Shlomo, Y, Churchyard, A, Head, J, Hurwitz, B, Overstall, P, Ockelford, J, Lees, A J (1998). Investigation by Parkinson's Disease Research Group of United Kingdom into excess mortality seen with combined levodopa and selegiline treatment in patients with early, mild Parkinson's disease: further results of randomised trial and confidential inquiry. BMJ 316: 1191-1196 [Full text]  
• STEUR, E. N H J., BALLERING, L. A P (1997). Moclobemide and selegeline in the treatment of depression in Parkinson's disease. J. Neurol. Neurosurg. Psychiatry 63: 547-547 [Full text]  
• , M. T S., , A. H V S., , P. J. (1997). Unexpected findings of study of selegiline have not been treated with caution its authors advised. BMJ 315: 370-370 [Full text]  
• Churchyard, A, Mathias, C J, Boonkongchuen, P, Lees, A J (1997). Autonomic effects of selegiline: possible cardiovascular toxicity in Parkinson's disease. J. Neurol. Neurosurg. Psychiatry 63: 228-234 [Abstract] [Full text]  
• Anderson, K E, Girdwood, A C, Wilson, J A (1996). Stopping selegiline may lead to problems for patients. BMJ 312: 702-702 [Full text]  
• Silva, M. T, Watts, P. M, Jenner, P. (1996). Parkinson's disease is rarely a primary cause of death. BMJ 312: 703-703 [Full text]  
• Jellinger, K A (1996). Causes of death need confirmation. BMJ 312: 704-704 [Full text]  
• Olanow, C W., Godbold, J. H, Koller, W. (1996). Patients taking selegiline may have received more levodopa than necessary. BMJ 312: 702a-703 [Full text]  
• Olanow, C W., Godbold, J. H, Koller, W. (1996). Patients taking selegiline may have received more levodopa than necessary. BMJ 312: 702b-703 [Full text]  
• Yu, P H, Lai, C T, Boulton, A A (1996). Selegiline may be toxic in presence of increased dopamine concentrations. BMJ 312: 703a-704 [Full text]  
• Yu, P H, Lai, C T, Boulton, A A (1996). Selegiline may be toxic in presence of increased dopamine concentrations. BMJ 312: 703b-704 [Full text]  
• Lees, A J, Head, J, Ben-Shlomo, Y (1996). Authors' reply. BMJ 312: 704a-705 [Full text]  
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• (1996). Selegiline May Not Be So Good for Early Parkinsonism. JWatch Psychiatry 1996: 16-16 [Full text]  
• (1996). SELEGILINE MAY NOT BE SO GOOD FOR EARLY PARKINSONISM. JWatch General 1996: 6-6 [Full text]