Pramipexole vs levodopa as initial treatment for Parkinson disease: a 4-year randomized controlled trial.
BACKGROUND
The best way to initiate dopaminergic therapy for early Parkinson disease remains unclear.


OBJECTIVE
To compare initial treatment with pramipexole vs levodopa in early Parkinson disease, followed by levodopa supplementation, with respect to the development of dopaminergic motor complications, other adverse events, and functional and quality-of-life outcomes.


METHODS
Multicenter, parallel-group, double-blind, randomized controlled trial.


METHODS
Academic movement disorders clinics at 22 sites in the United States and Canada.


METHODS
Patients with early Parkinson disease (N = 301) who required dopaminergic therapy to treat emerging disability, enrolled between October 1996 and August 1997 and observed until August 2001.


METHODS
Subjects were randomly assigned to receive 0.5 mg of pramipexole 3 times per day with levodopa placebo (n = 151) or 25/100 mg of carbidopa/levodopa 3 times per day with pramipexole placebo (n = 150). Dosage was escalated during the first 10 weeks for patients with ongoing disability. Thereafter, investigators were permitted to add open-label levodopa or other antiparkinsonian medications to treat ongoing or emerging disability.


METHODS
Time to the first occurrence of dopaminergic complications: wearing off, dyskinesias, on-off fluctuations, and freezing; changes in the Unified Parkinson's Disease Rating Scale and quality-of-life scales; and adverse events.


RESULTS
Initial pramipexole treatment resulted in a significant reduction in the risk of developing dyskinesias (24.5% vs 54%; hazard ratio, 0.37; 95% confidence interval [CI], 0.25-0.56; P<.001) and wearing off (47% vs 62.7%; hazard ratio, 0.68; 95% CI, 0.49-0.63; P =.02). Initial levodopa treatment resulted in a significant reduction in the risk of freezing (25.3% vs 37.1%; hazard ratio, 1.7; 95% CI, 1.11-2.59; P =.01). By 48 months, the occurrence of disabling dyskinesias was uncommon and did not significantly differ between the 2 groups. The mean improvement in the total Unified Parkinson's Disease Rating Scale score from baseline to 48 months was greater in the levodopa group than in the pramipexole group (2 +/- 15.4 points vs -3.2 +/- 17.3 points, P =.003). Somnolence (36% vs 21%, P =.005) and edema (42% vs 15%, P<.001) were more common in pramipexole-treated subjects than in levodopa-treated subjects. Mean changes in quality-of-life scores did not differ between the groups.


CONCLUSIONS
Initial treatment with pramipexole resulted in lower incidences of dyskinesias and wearing off compared with initial treatment with levodopa. Initial treatment with levodopa resulted in lower incidences of freezing, somnolence, and edema and provided for better symptomatic control, as measured by the Unified Parkinson's Disease Rating Scale, compared with initial treatment with pramipexole. Both options resulted in similar quality of life. Levodopa and pramipexole both appear to be reasonable options as initial dopaminergic therapy for Parkinson disease, but they are associated with different efficacy and adverse-effect profiles.
Holloway
Robert G
RG
Department of Neurology, University of Rochester, 1351 Mt. Hope Avenue, Suite 220, Rochester, NY 14620, USA. robert.holloway@ctcc.rochester.edu
Shoulson
Ira
I
Fahn
Stanley
S
Kieburtz
Karl
K
Lang
Anthony
A
Marek
Kenneth
K
McDermott
Michael
M
Seibyl
John
J
Weiner
William
W
Musch
Bruno
B
Kamp
Cornelia
C
Welsh
Mickie
M
Shinaman
Aileen
A
Pahwa
Rajesh
R
Barclay
Lynn
L
Hubble
Jean
J
LeWitt
Peter
P
Miyasaki
Janis
J
Suchowersky
Oksana
O
Stacy
Mark
M
Russell
David S
DS
Ford
Blair
B
Hammerstad
John
J
Riley
David
D
Standaert
David
D
Wooten
Frederick
F
Factor
Stewart
S
Jankovic
Joseph
J
Atassi
Farah
F
Kurlan
Roger
R
Panisset
Michel
M
Rajput
Ali
A
Rodnitzky
Robert
R
Shults
Cliff
C
Petsinger
Giselle
G
Waters
Cheryl
C
Pfeiffer
Ronald
R
Biglan
Kevin
K
Borchert
Leona
L
Montgomery
Amy
A
Sutherland
Laura
L
Weeks
Carolyn
C
DeAngelis
Maryan
M
Sime
Elspeth
E
Wood
Susan
S
Pantella
Carol
C
Harrigan
Mary
M
Fussell
Barbara
B
Dillon
Sandra
S
Alexander-Brown
Barbara
B
Rainey
Pamela
P
Tennis
Marsha
M
Rost-Ruffner
Elke
E
Brown
Diane
D
Evans
Sharon
S
Berry
Debra
D
Hall
Jean
J
Shirley
Theresa
T
Dobson
Judith
J
Fontaine
Deborah
D
Pfeiffer
Brenda
B
Brocht
Alicia
A
Bennett
Susan
S
Daigneault
Susan
S
Hodgeman
Karen
K
O'Connell
Carolynn
C
Ross
Tori
T
Richard
Karen
K
Watts
Arthur
A
D000368:Aged; D052160:Benzothiazoles; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007980:Levodopa / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D000077487:Pramipexole; D016016:Proportional Hazards Models; D011788:Quality of Life / Q000523:psychology; D012720:Severity of Illness Index; D013844:Thiazoles / Q000009:adverse effects / Q000627:therapeutic use*
D052160:Benzothiazoles; D013844:Thiazoles; D007980:Levodopa; D000077487:Pramipexole