This Article  • References  • Full text PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Contact me when this article is cited  Related Content  • Similar articles in JAMA  Social Bookmarking   What's this?

A Randomized Dose-Ranging Study

Parkinson Study Group

JAMA. 1997;278(2):125-130.

Abstract
Context.
—Monotherapy with dopamine agonists may be useful in early Parkinson disease.

Objective.
—To evaluate dose-response relationships for tolerability, safety, and efficacy of the synthetic dopamine agonist pramipexole.

Design.
—Multicenter, multidosage, parallel-group, double-blind, placebocontrolled, randomized clinical trial.

Setting.
—University or academically based movement disorder clinics.

Patients.
—A total of 264 patients with early Parkinson disease (PD) who were not requiring or receiving levodopa or other dopamine agonists were enrolled.

Intervention.
—Subjects were randomized to 1 of 5 treatment groups: pramipexole doses of 1.5 mg/d, 3.0 mg/d, 4.5 mg/d, and 6.0 mg/d, or matching placebo. A 6-week dosage escalation period was followed by a 4-week maintenance period and a 1-week period during which active treatment was withdrawn.

Main Outcome Measures.
—The primary measure of tolerability was the proportion of subjects completing the study on the assigned treatment. The primary measure of efficacy was the change from baseline to 10 weeks in the total score on the Unified Parkinson's Disease Rating Scale (UPDRS).

Results.
—Pramipexole was generally safe and well tolerated in this 10-week study. The proportion of subjects completing the study on the originally assigned dosage was 98% for placebo and 81% for the 1.5-mg/d, 92% for the 3.0-mg/d, 78% for the 4.5-mg/d, and 67% for the 6.0-mg/d treatment groups. There was a trend toward increased frequency of adverse experiences, particularly somnolence, in the 6.0-mg/d group. After 10 weeks of treatment, pramipexole-treated subjects showed a 20% improvement in total UPDRS scores, with mean improvements in scores ranging from 5.9 to 7.0 units among active treatment groups, compared with 0.9 units for the placebo group (P<.005 for each comparison with placebo). There was also evidence that the treatment effects were more pronounced in subjects with worse UPDRS scores at baseline.

Conclusions.
—Pramipexole is safe and effective as short-term monotherapy in patients with early PD who are not receiving levodopa. Further study is warranted to determine the long-term impact of pramipexole on the progression of disability in PD and its value in comparison with levodopa therapy and other dopamine agonists.

Footnotes
A complete list of the Parkinson Study Group authors appears at the end of this article.

Reprints: Karl Kieburtz, MD, Department of Neurology, University of Rochester Medical Center, 601 Elmwood Ave, Box 673, Rochester, NY 14642.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

The scientific and clinical basis for the treatment of Parkinson disease (2009)
Olanow et al.
Neurology 2009;72:S1-S136.
ABSTRACT | FULL TEXT  

Pharmacologic Management of Parkinson Disease: Choice of Initial Therapy in Early Disease
Chen and Pahwa
Journal of Pharmacy Practice 2008;21:244-253.
ABSTRACT  

Risk factors for somnolence, edema, and hallucinations in early Parkinson disease
Biglan et al.
Neurology 2007;69:187-195.
ABSTRACT | FULL TEXT  

Risk Factors for the Development of Pedal Edema in Patients Using Pramipexole
Kleiner-Fisman and Fisman
Arch Neurol 2007;64:820-824.
ABSTRACT | FULL TEXT  

Comparison of pramipexole and modafinil on arousal, autonomic, and endocrine functions in healthy volunteers
Samuels et al.
J Psychopharmacol 2006;20:756-770.
ABSTRACT  

Dopamine Agonist Therapy in Low-Response Children Following Traumatic Brain Injury
Patrick et al.
J Child Neurol 2006;21:879-885.
ABSTRACT  

Clinical trials aimed at detecting neuroprotection in Parkinson's disease
Hauser and Zesiewicz
Neurology 2006;66:S58-S68.
ABSTRACT | FULL TEXT  

Measuring therapy adherence in Parkinson's disease: a comparison of methods
Grosset et al.
J. Neurol. Neurosurg. Psychiatry 2006;77:249-251.
ABSTRACT | FULL TEXT  

A Controlled Trial of Rotigotine Monotherapy in Early Parkinson's Disease
The Parkinson Study Group
Arch Neurol 2003;60:1721-1728.
ABSTRACT | FULL TEXT  

A Controlled Trial of Rasagiline in Early Parkinson Disease: The TEMPO Study
Parkinson Study Group
Arch Neurol 2002;59:1937-1943.
ABSTRACT | FULL TEXT  

Effects of Coenzyme Q10 in Early Parkinson Disease: Evidence of Slowing of the Functional Decline
Shults et al.
Arch Neurol 2002;59:1541-1550.
ABSTRACT | FULL TEXT  

Pramipexole in patients with Parkinson's disease and marked drug resistant tremor: a randomised, double blind, placebo controlled multicentre study
Pogarell et al.
J. Neurol. Neurosurg. Psychiatry 2002;72:713-720.
ABSTRACT | FULL TEXT  

Clinical trial end points: On the road to nowhere?
Holloway and Dick
Neurology 2002;58:679-686.
ABSTRACT | FULL TEXT  

Levodopa strengths and weaknesses
Jankovic
Neurology 2002;58:S19-32.
ABSTRACT | FULL TEXT  

The role of dopamine agonists in the treatment of early Parkinson's disease
Olanow
Neurology 2002;58:S33-41.
ABSTRACT | FULL TEXT  

Long-term studies of dopamine agonists
Hubble
Neurology 2002;58:S42-50.
ABSTRACT | FULL TEXT  

Dopamine agonists and sleep in Parkinson's disease
Cantor and Stern
Neurology 2002;58:S71-78.
ABSTRACT | FULL TEXT  

An algorithm (decision tree) for the management of Parkinson's disease (2001):: Treatment
Olanow et al.
Neurology 2001;56:S1-S88.
FULL TEXT  

Pramipexole Augmentation in Panic With Agoraphobia
MARAZZITI et al.
Am. J. Psychiatry 2001;158:498-a-499.
FULL TEXT  

A randomized, controlled trial of remacemide for motor fluctuations in Parkinson's disease
Neurology 2001;56:455-462.
ABSTRACT | FULL TEXT  

Safety of pramipexole in patients with restless legs syndrome
Stiasny et al.
Neurology 2000;55:1589-1590.
FULL TEXT  

Pramipexole vs Levodopa as Initial Treatment for Parkinson Disease: A Randomized Controlled Trial
Parkinson Study Group
JAMA 2000;284:1931-1938.
ABSTRACT | FULL TEXT  

Dopamine Agonists in Early Therapy for Parkinson Disease: Promise and Problems
Tanner
JAMA 2000;284:1971-1973.
FULL TEXT  

Clinical Characteristics of Pramipexole-Induced Peripheral Edema
Tan and Ondo
Arch Neurol 2000;57:729-732.
ABSTRACT | FULL TEXT  

Is Levodopa Toxic?
Weiner
Arch Neurol 2000;57:408-410.
FULL TEXT  

Falling asleep at the wheel: Motor vehicle mishaps in people taking pramipexole and ropinirole
Olanow et al.
Neurology 2000;54:274-274.
FULL TEXT  

New and Emerging Therapies for Parkinson Disease
Jankovic
Arch Neurol 1999;56:785-790.
ABSTRACT | FULL TEXT  

Falling asleep at the wheel: Motor vehicle mishaps in persons taking pramipexole and ropinirole
Frucht et al.
Neurology 1999;52:1908-1908.
ABSTRACT | FULL TEXT  

Developments in the treatment of Parkinson's disease
DTB 1999;37:36-40.
ABSTRACT | FULL TEXT  

Pramipexole in Refractory Bipolar Depression
GOLDBERG et al.
Am. J. Psychiatry 1999;156:798-798.
FULL TEXT  

Efficacy, safety, and tolerance of the non-ergoline dopamine agonist pramipexole in the treatment of advanced Parkinson's disease: a double blind, placebo controlled, randomised, multicentre study
Pinter et al.
J. Neurol. Neurosurg. Psychiatry 1999;66:436-441.
ABSTRACT | FULL TEXT  

Restless legs syndrome improved by pramipexole: A double-blind randomized trial
Montplaisir et al.
Neurology 1999;52:938-938.
ABSTRACT | FULL TEXT  

PRAMIPEXOLE SAFE AND EFFECTIVE FOR EARLY PARKINSON DISEASE
JWatch General 1997;1997:5-5.
FULL TEXT