Effect of selegiline on mortality in patients with Parkinson's disease: a meta-analysis.
BACKGROUND
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.


CONCLUSIONS
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.
Olanow
C W
CW
Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Myllylä
V V
VV
Sotaniemi
K A
KA
Larsen
J P
JP
Pålhagen
S
S
Przuntek
H
H
Heinonen
E H
EH
Kilkku
O
O
Lammintausta
R
R
Mäki-Ikola
O
O
Rinne
U K
UK
D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy / Q000401:mortality*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D012642:Selegiline / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D015996:Survival Rate
D000978:Antiparkinson Agents; D008996:Monoamine Oxidase Inhibitors; D018696:Neuroprotective Agents; D012642:Selegiline; D007980:Levodopa