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.


METHODS
Open, long term, prospective randomised trial.


METHODS
93 hospitals throughout United Kingdom.


METHODS
520 patients with early Parkinson's disease who were not receiving dopaminergic treatment.


METHODS
Treatment with levodopa and dopa decarboxylase inhibitor (arm 1) or levodopa and decarboxylase inhibitor in combination with selegiline (arm 2).


METHODS
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.
Lees
A J
AJ
Parkinson's Disease Research Group of the United Kingdom, National Hospital for Neurology and Neurosurgery, London.
D000978:Antiparkinson Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001545:Benserazide / Q000008:administration & dosage / Q000627:therapeutic use; D001971:Bromocriptine / Q000008:administration & dosage / Q000627:therapeutic use; D002423:Cause of Death; D004185:Disability Evaluation; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage / Q000627:therapeutic use*; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy* / Q000401:mortality*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012642:Selegiline / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D013997:Time Factors; D017211:Treatment Failure
D000978:Antiparkinson Agents; D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline; D001971:Bromocriptine; D007980:Levodopa; D001545:Benserazide