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Effect of selegiline on mortality in patients with Parkinson's disease

A meta-analysis

From the Department of Neurology (Dr. Olanow), Mount Sinai School of Medicine, New York, NY; Department of Neurology (Drs. Myllylä and Sotaniemi), Oulu University Hospital, Oulu, Finland; Department of Neurology (Dr. Larsen), Central Hospital of Rogaland, Stavanger, Norway; Department of Neurology (Dr. Pålhagen), Ryhov Hospital, Jönköping, Sweden; Department of Neurology (Dr. Przuntek), Ruhr University, Bochum, Germany; and Orion Pharmaceuticals (Drs. Heinonen, Kilkku, Lammintausta, and Mäki-Ikola) and Department of Neurology (Dr. Rinne), University of Turku, Turku, Finland.

Address correspondence and reprint requests to Dr. C. Warren Olanow, Professor and Chairman, Department of Neurology, Mount Sinai School of Medicine, 1 Gustave Levy Place, Box 1137, New York, NY 10029.

Introduction: The Parkinson's Disease Research Group of the United Kingdom (PDRG-UK) reported increased mortality in PD patients treated with levodopa plus selegiline compared with those treated with levodopa alone.

Methods: We performed a meta-analysis on five long-term, prospective, randomized trials of selegiline in patients with untreated PD. Included in the analysis were four randomized, double-blind, placebo-controlled studies and one randomized, double-blind, placebo-controlled study of 2 years' duration followed by long-term, open follow-up.

Results: The mean duration of follow-up was 4.1 ± 1.8 years. There were 14 deaths in 297 selegiline-treated patients (4.7%) and 17 deaths in 292 non-selegiline-treated patients (5.8%). The hazard ratio for mortality was 1.02 (95% CI 0.44 to 2.37; p = 0.96). An analysis restricted to patients receiving only levodopa with or without selegiline noted 11 deaths in 257 levodopa/selegiline-treated patients (4.3%) and 11 deaths in 254 patients treated with levodopa alone (4.3%). The hazard ratio was 1.06(95% CI 0.44 to 2.55; p = 0.90). Death rate per 1,000 patient years was 11.4 in the selegiline group and 14.2 in the nonselegiline group. Kaplan-Meier survival curves reflecting pooled survival data showed no significant difference in duration of survival. The hazard ratio was 0.84(95% CI 0.41 to 1.70; p = 0.63) for selegiline-versus non-selegiline-treated patients and 1.05 (95% CI 0.46 to 2.43;p = 0.91) for selegiline/levodopa- versus levodopa-treated patients.

Conclusion: These results contrast with those of the PDRG-UK study and demonstrate no increase in mortality associated with selegiline treatment whether or not patients also received levodopa.

*See the Appendix on page 829 for the names of participants in the study groups.

Received April 14, 1997. Accepted in final form May 13, 1998.

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