Selegiline delays the onset of disability in de novo parkinsonian patients

被引:119
作者
Pålhagen, S [1 ]
Heinonen, EH
Hägglund, J
Kaugesaar, T
Kontants, H
Mäki-Ikola, O
Palm, R
Turunen, J
机构
[1] Ryhov Hosp, Dept Neurol, S-55185 Jonkoping, Sweden
[2] Orion Corp Farmos, ORION PHARMA, Turku, Finland
[3] Orion Corp Farmos, ORION PHARMA, Stockholm, Sweden
[4] Linkoping Univ Hosp, Dept Neurol, Linkoping, Sweden
[5] Malar Hosp, Eskilstuna, Sweden
[6] Cent Hosp, Dept Neurol & Rehabil, Karlstad, Sweden
关键词
D O I
10.1212/WNL.51.2.520
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Objective: The objective of this study was to investigate the effect of selegiline first as monotherapy and then in combination with levodopa in the early phase of PD. Methods: A total of 157 de novo PD patients were randomized to receive either selegiline or placebo in a double-blind study until levodopa therapy became necessary. Thereafter, the drugs were withdrawn for an 8-week washout period to evaluate the possible symptomatic effect of selegiline. Results: Analysis of Kaplan-Meier survival curves for each group showed that selegiline delayed significantly the need for levodopa therapy (p = 0.028). The semiannual rate of disability progression was slowed down significantly in the selegiline group analyzed with the Unified Parkinson's Disease Rating Scale (total and motor scores, p < 0.001). Selegiline had a "wash-in" effect (i.e., an initial symptomatic amelioration of PD at 6 weeks and 3 months). However, after the 8-week washout period, no significant differences in the deterioration of disability between the groups was revealed in any of the scales, suggesting that besides having a slight symptomatic effect, selegiline mag also have neuroprotective effects. Similarly, the progression of symptoms from baseline to the end of the washout period was significantly slower (p = 0.033) in the selegiline group when the progression was adjusted by the time to reach the end point. Selegiline was well tolerated. Conclusions: Selegiline delayed significantly the need to start levodopa in early PD. After a 2-month washout period (before the start of levodopa therapy) no significant symptomatic effect of selegiline was seen in comparison with the placebo group, supporting the concept of neuroprotective properties of the drug.
引用
收藏
页码:520 / 525
页数:6
相关论文
共 25 条
[1]  
[Anonymous], 1989, Quantification of Neurological Deficit
[2]  
[Anonymous], NEUROLOGY S
[3]   COMPARATIVE-STUDY OF SELEGILINE PLUS L-DOPA-CARBIDOPA VERSUS L-DOPA-CARBIDOPA ALONE IN THE TREATMENT OF PARKINSONS-DISEASE [J].
BRANNAN, T ;
YAHR, MD .
ANNALS OF NEUROLOGY, 1995, 37 (01) :95-98
[4]  
DAGHER A, 1996, NEUROLOGY, P46
[5]   MINI-MENTAL STATE - PRACTICAL METHOD FOR GRADING COGNITIVE STATE OF PATIENTS FOR CLINICIAN [J].
FOLSTEIN, MF ;
FOLSTEIN, SE ;
MCHUGH, PR .
JOURNAL OF PSYCHIATRIC RESEARCH, 1975, 12 (03) :189-198
[6]   SLOW RECOVERY OF HUMAN BRAIN MAO-B AFTER L-DEPRENYL (SELEGELINE) WITHDRAWAL [J].
FOWLER, JS ;
VOLKOW, ND ;
LOGAN, J ;
WANG, GJ ;
MACGREGOR, RR ;
SCHLYER, D ;
WOLF, AP ;
PAPPAS, N ;
ALEXOFF, D ;
SHEA, C ;
DORFLINGER, E ;
KRUCHOWY, L ;
YOO, K ;
FAZZINI, E ;
PATLAK, C .
SYNAPSE, 1994, 18 (02) :86-93
[7]   METHODS OF ASSESSING THE EFFECT OF DRUG-THERAPY ON QUALITY OF LIFE [J].
GANZ, PA .
DRUG SAFETY, 1990, 5 (04) :233-242
[8]   A RATING SCALE FOR DEPRESSION [J].
HAMILTON, M .
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 1960, 23 (01) :56-62
[9]   PARKINSONISM - ONSET PROGRESSION AND MORTALITY [J].
HOEHN, MM ;
YAHR, MD .
NEUROLOGY, 1967, 17 (05) :427-&
[10]   The effects of early selegiline therapy on long-term levodopa treatment and parkinsonian disability: An interim analysis of a Norwegian-Danish 5-year study [J].
Larsen, JP ;
Boas, J ;
Aasly, J ;
Boesen, F ;
Boisen, E ;
Borgmann, R ;
Dupont, E ;
Erdal, JE ;
Gilhus, NE ;
Heinonen, E ;
Hunstad, N ;
Kilkku, O ;
Mai, J ;
Mellgren, SI ;
Mikkelsen, B ;
Nessler, E ;
Selseth, B ;
Vilming, S ;
Wermuth, L ;
WormPetersen, J ;
Okseter, K .
MOVEMENT DISORDERS, 1997, 12 (02) :175-182