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BMJ. 1995 December 16; 311(7020): 1602–1607.
PMCID: PMC2551499

Comparison of therapeutic effects and mortality data of levodopa and levodopa combined with selegiline in patients with early, mild Parkinson's disease. Parkinson's Disease Research Group of the United Kingdom.


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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Selected References

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