This Article  • 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  • Related letter  • Related articles  • Similar articles in JAMA  Topic Collections  • Neurology  • Randomized Controlled Trial  • Alert me on articles by topic

A Randomized Controlled Trial

Parkinson Study Group

JAMA. 2000;284:1931-1938.

Context  Pramipexole and levodopa both ameliorate the motor symptoms of early Parkinson disease (PD), but no controlled studies have compared long-term outcomes after initiating dopaminergic therapy with pramipexole vs levodopa.

Objective  To compare the development of dopaminergic motor complications after initial treatment of early PD with pramipexole vs levodopa.

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

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

Patients  Three hundred one patients with early PD who required dopaminergic therapy to treat emerging disability, enrolled between October 1996 and August 1997.

Interventions  Subjects were randomly assigned to receive pramipexole, 0.5 mg 3 times per day, with levodopa placebo (n = 151); or carbidopa/levodopa, 25/100 mg 3 times per day, with pramipexole placebo (n = 150). For patients with residual disability, the dosage was escalated during the first 10 weeks. From week 11 to month 23.5, investigators were permitted to add open-label levodopa to treat continuing or emerging disability.

Main Outcome Measures  Time to the first occurrence of any of 3 dopaminergic complications: wearing off, dyskinesias, or on-off motor fluctuations; changes in scores on the Unified Parkinson's Disease Rating Scale (UPDRS), assessed at baseline and follow-up evaluations; and, in a subgroup of 82 subjects evaluated at baseline and 23.5 months, ratio of specific to nondisplaceable striatal iodine 123 2--carboxymethoxy-3--(4-iodophenyl)tropane (-CIT) uptake on single photon emission computed tomography imaging of the dopamine transporter.

Results  Initial pramipexole treatment resulted in significantly less development of wearing off, dyskinesias, or on-off motor fluctuations (28%) compared with levodopa (51%) (hazard ratio, 0.45; 95% confidence interval [CI], 0.30-0.66; P<.001). The mean improvement in total UPDRS score from baseline to 23.5 months was greater in the levodopa group than in the pramipexole group (9.2 vs 4.5 points; P<.001). Somnolence was more common in pramipexole-treated patients than in levodopa-treated patients (32.4% vs 17.3%; P = .003), and the difference was seen during the escalation phase of treatment. In the subgroup study, patients treated initially with pramipexole (n = 39) showed a mean (SD) decline of 20.0% (14.2%) in striatal -CIT uptake compared with a 24.8% (14.4%) decline in subjects treated initially with levodopa (n = 39; P = .15).

Conclusions  Fewer patients receiving initial treatment for PD with pramipexole developed dopaminergic motor complications than with levodopa therapy. Despite supplementation with open-label levodopa in both groups, the levodopa-treated group had a greater improvement in total UPDRS compared with the pramipexole group.

RELATED LETTER

Brain Imaging to Assess the Effects of Dopamine Agonists on Progression of Parkinson Disease
J. Eric Ahlskog, Demetrius M. Maraganore, Ryan J. Uitti, George R. Uhl, Roger L. Albin, Thomas E. Nichols, Kirk A. Frey, Paul K. Morrish, Kenneth Marek, John Seibyl, Michael McDermott, Stanley Fahn, and Anthony Lang
JAMA. 2002;288(3):311-313.
EXTRACT | FULL TEXT  

RELATED ARTICLES

Dopamine Agonists in Early Therapy for Parkinson Disease: Promise and Problems
Caroline M. Tanner
JAMA. 2000;284(15):1971-1973.
EXTRACT | FULL TEXT  

October 18, 2000
JAMA. 2000;284(15):1993-1994.
EXTRACT | FULL TEXT  

Parkinson Disease
JAMA. 2000;284(15):2012.
PDF  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Assessing Multiple Medication Use With Probabilities of Benefits and Harms
Murphy et al.
J Aging Health 2008;20:694-709.
ABSTRACT  

Agonist or levodopa for Parkinson disease?: Ultimately, it doesn't matter; neither is good enough
Weiner and Reich
Neurology 2008;71:470-471.
FULL TEXT  

Fourteen-year final report of the randomized PDRG-UK trial comparing three initial treatments in PD
Katzenschlager et al.
Neurology 2008;71:474-480.
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  

A review of Parkinson's disease
Davie
Br Med Bull 2008;86:109-127.
ABSTRACT | FULL TEXT  

Invited Article: Changing concepts in Parkinson disease: Moving beyond the Decade of the Brain
Marras and Lang
Neurology 2008;70:1996-2003.
ABSTRACT | FULL TEXT  

Role of the Pharmacist in the Effective Management of Wearing-Off in Parkinson's Disease
Simonson et al.
The Annals of Pharmacotherapy 2007;41:1842-1849.
ABSTRACT | FULL TEXT  

Presentation and Management of Psychosis in Parkinson's Disease and Dementia With Lewy Bodies
Weintraub and Hurtig
Am. J. Psychiatry 2007;164:1491-1498.
FULL TEXT  

Peripheral Edema and Dopamine Agonists in Parkinson Disease
Tan
Arch Neurol 2007;64:1546-1547.
FULL TEXT  

Treatment Options in the Modern Management of Parkinson Disease
Schapira
Arch Neurol 2007;64:1083-1088.
FULL TEXT  

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  

Transdermal Rotigotine: Double-blind, Placebo-Controlled Trial in Parkinson Disease
Jankovic et al.
Arch Neurol 2007;64:676-682.
ABSTRACT | FULL TEXT  

The Implications of Using US-Specific EQ-5D Preference Weights for Cost-Effectiveness Evaluation
Noyes et al.
Med Decis Making 2007;27:327-334.
ABSTRACT  

Rotigotine: Transdermal Dopamine Agonist Treatment of Parkinson's Disease and Restless Legs Syndrome
Splinter
The Annals of Pharmacotherapy 2007;41:285-295.
ABSTRACT | FULL TEXT  

Randomized, blind, controlled trial of transdermal rotigotine in early Parkinson disease
Watts et al.
Neurology 2007;68:272-276.
ABSTRACT | FULL TEXT  

Factors Associated With the Development of Motor Fluctuations and Dyskinesias in Parkinson Disease
Hauser et al.
Arch Neurol 2006;63:1756-1760.
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  

Initial pharmacotherapy in a population of veterans with Parkinson disease
Swarztrauber et al.
Neurology 2006;66:1425-1426.
ABSTRACT | FULL TEXT  

Selegiline slows the progression of the symptoms of Parkinson disease
Palhagen et al.
Neurology 2006;66:1200-1206.
ABSTRACT | FULL TEXT  

Practice Parameter: neuroprotective strategies and alternative therapies for Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.
Suchowersky et al.
Neurology 2006;66:976-982.
ABSTRACT | FULL TEXT  

Clinical management of Parkinson's disease dementia: pitfalls and progress
Samuel et al.
Adv. Psychiatr. Treat. 2006;12:121-129.
ABSTRACT | FULL TEXT  

Levodopa-Associated Dyskinesia Risk Among Parkinson Disease Patients in Olmsted County, Minnesota, 1976-1990
Van Gerpen et al.
Arch Neurol 2006;63:205-209.
ABSTRACT | FULL TEXT  

Non-linearity of Parkinson's disease progression: implications for sample size calculations in clinical trials
Guimaraes et al.
Clin Trials 2005;2:509-518.
ABSTRACT  

Sudden Uncontrollable Somnolence and Medication Use in Parkinson Disease
Avorn et al.
Arch Neurol 2005;62:1242-1248.
ABSTRACT | FULL TEXT  

A novel dopamine agonist for the transdermal treatment of Parkinson's disease
Jenner
Neurology 2005;65:S3-S5.
ABSTRACT | FULL TEXT  

Clinical studies with transdermal rotigotine in early Parkinson's disease
Poewe and Luessi
Neurology 2005;65:S11-S14.
FULL TEXT  

Intermittent vs Continuous Levodopa Administration in Patients With Advanced Parkinson Disease: A Clinical and Pharmacokinetic Study
Stocchi et al.
Arch Neurol 2005;62:905-910.
ABSTRACT | FULL TEXT  

"Levodopa phobia": A new iatrogenic cause of disability in Parkinson disease
Kurlan
Neurology 2005;64:923-924.
FULL TEXT  

Nonlinear Progression of Parkinson Disease as Determined by Serial Positron Emission Tomographic Imaging of Striatal Fluorodopa F 18 Activity
Hilker et al.
Arch Neurol 2005;62:378-382.
ABSTRACT | FULL TEXT  

The role of radiotracer imaging in Parkinson disease
Ravina et al.
Neurology 2005;64:208-215.
ABSTRACT | FULL TEXT  

Initial Treatment of Parkinson Disease: Levodopa or Dopamine Agonists
Weiner
Arch Neurol 2004;61:1966-1969.
FULL TEXT  

Dopamine Agonists Modify the Course of Parkinson Disease
Stern
Arch Neurol 2004;61:1969-1971.
FULL TEXT  

The comparative effects of medical therapies for Parkinson's disease
Horn and Stern
Neurology 2004;63:S7-S12.
FULL TEXT  

Clinical trials of neuroprotection for Parkinson's disease
LeWitt
Neurology 2004;63:S23-S31.
FULL TEXT  

Pramipexole v. Levodopa as Initial Treatment for Parkinson's Disease: A Randomized Clinical-Economic Trial
Noyes et al.
Med Decis Making 2004;24:472-485.
ABSTRACT  

Double-blind, Placebo-Controlled Study of Entacapone in Levodopa-Treated Patients With Stable Parkinson Disease
Olanow et al.
Arch Neurol 2004;61:1563-1568.
ABSTRACT | FULL TEXT  

Neuropsychiatric Complications of Medical and Surgical Therapies for Parkinson's Disease
Burn and Troster
J Geriatr Psychiatry Neurol 2004;17:172-180.
ABSTRACT  

Improvement of motor function in early Parkinson disease by safinamide
Stocchi et al.
Neurology 2004;63:746-748.
ABSTRACT | FULL TEXT  

Biomarkers and Parkinson's disease
Michell et al.
Brain 2004;127:1693-1705.
ABSTRACT | FULL TEXT  

Pramipexole vs Levodopa as Initial Treatment for Parkinson Disease: A 4-Year Randomized Controlled Trial
The Parkinson Study Group
Arch Neurol 2004;61:1044-1053.
ABSTRACT | FULL TEXT  

Slowing Parkinson's disease progression: Recent dopamine agonist trials
Montgomery et al.
Neurology 2004;62:343-345.
FULL TEXT  

Neuroprotection in Parkinson Disease: Mysteries, Myths, and Misconceptions
Schapira and Olanow
JAMA 2004;291:358-364.
ABSTRACT | FULL TEXT  

Unmet medical needs in Parkinson's disease
Koller and Tse
Neurology 2004;62:S1-8.
ABSTRACT | FULL TEXT  

New developments in levodopa therapy
LeWitt and Nyholm
Neurology 2004;62:S9-16.
ABSTRACT | FULL TEXT  

The role of COMT inhibition in the treatment of Parkinson's disease
Poewe
Neurology 2004;62:S31-38.
ABSTRACT | FULL TEXT  

Continuous dopaminergic stimulation in early and advanced Parkinson's disease
Stocchi and Olanow
Neurology 2004;62:S56-63.
ABSTRACT | FULL TEXT  

Introduction: Adenosine A2A receptor modulation of motor systems for symptomatic therapy in Parkinson's disease
Standaert
Neurology 2003;61:S30-31.
FULL TEXT  

Treatments of Parkinson Disease: Circa 2003
Shults
Arch Neurol 2003;60:1680-1684.
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  

Agonists versus levodopa in PD: The thrilla of whitha
Montgomery et al.
Neurology 2003;61:1462-1463.
FULL TEXT  

Orthostatic Hypotension in De Novo Parkinson Disease
Bonuccelli et al.
Arch Neurol 2003;60:1400-1404.
ABSTRACT | FULL TEXT  

The MPTP-treated primate as a model of motor complications in PD: Primate model of motor complications
Jenner
Neurology 2003;61:S4-11.
ABSTRACT | FULL TEXT  

Clinical strategies to prevent and delay motor complications
Barone
Neurology 2003;61:S12-16.
ABSTRACT | FULL TEXT  

Present and future directions in the management of motor complications in patients with advanced PD
Olanow
Neurology 2003;61:S24-33.
FULL TEXT  

Neuroprotection in PD--A role for dopamine agonists?
Schapira
Neurology 2003;61:S34-42.
FULL TEXT  

Imaging the dopamine system to assess disease-modifying drugs: Studies comparing dopamine agonists and levodopa
Marek et al.
Neurology 2003;61:S43-48.
FULL TEXT  

Disease-modifying strategies and challenges in PD: Interactive breakout sessions
Schapira
Neurology 2003;61:S56-63.
FULL TEXT  

Neuroprotective agents for clinical trials in Parkinson's disease: A systematic assessment
Ravina et al.
Neurology 2003;60:1234-1240.
ABSTRACT | FULL TEXT  

Update on Parkinson Disease
Siderowf and Stern
ANN INTERN MED 2003;138:651-658.
ABSTRACT | FULL TEXT  

Agonists vs levodopa in PD: The thrilla of whitha
Wooten
Neurology 2003;60:360-362.
FULL TEXT  

Slowing Parkinson's disease progression: Recent dopamine agonist trials
Ahlskog
Neurology 2003;60:381-389.
ABSTRACT | FULL TEXT  

Initial agonist treatment of Parkinson disease: A critique
Albin and Frey
Neurology 2003;60:390-394.
ABSTRACT | FULL TEXT  

Current concepts in the diagnosis and management of Parkinson's disease
Guttman et al.
CMAJ 2003;168:293-301.
ABSTRACT | FULL TEXT  

Measuring motor complications in clinical trials for early Parkinson's disease
Marras and Lang
J. Neurol. Neurosurg. Psychiatry 2003;74:143-146.
FULL TEXT  

A possible substrate for dopamine-related changes in mood and behavior: Prefrontal and limbic effects of a D3-preferring dopamine agonist
Black et al.
Proc. Natl. Acad. Sci. USA 2002;99:17113-17118.
ABSTRACT | FULL TEXT  

Drugs for Parkinson's disease
Lees
J. Neurol. Neurosurg. Psychiatry 2002;73:607-610.
FULL TEXT  

Long term tolerability of high dose ergoline derived dopamine agonist therapy for the treatment of Parkinson's disease
Navan and Bain
J. Neurol. Neurosurg. Psychiatry 2002;73:602-603.
FULL TEXT  

Practice parameter: Initiation of treatment for Parkinson's disease: An evidence-based review
Inzelberg et al.
Neurology 2002;59:1292-1292.
FULL TEXT  

Prospective randomized trial of lisuride infusion versus oral levodopa in patients with Parkinson's disease
Stocchi et al.
Brain 2002;125:2058-2066.
ABSTRACT | FULL TEXT  

Brain Imaging to Assess the Effects of Dopamine Agonists on Progression of Parkinson Disease
Ahlskog et al.
JAMA 2002;288:311-313.
FULL TEXT  

Preference-based quality-of-life in patients with Parkinson's disease
Siderowf et al.
Neurology 2002;59:103-108.
ABSTRACT | FULL TEXT  

Sleep attacks in patients taking dopamine agonists: review
Homann et al.
BMJ 2002;324:1483-1487.
ABSTRACT | FULL TEXT  

Dopamine Transporter Brain Imaging to Assess the Effects of Pramipexole vs Levodopa on Parkinson Disease Progression
Parkinson Study Group
JAMA 2002;287:1653-1661.
ABSTRACT | FULL TEXT  

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

MEDICAL MANAGEMENT OF PARKINSON'S DISEASE
Clarke
J. Neurol. Neurosurg. Psychiatry 2002;72:i22-27.
FULL TEXT  

Pharmacology of dopamine agonists in the treatment of Parkinson's disease
Jenner
Neurology 2002;58:S1-8.
ABSTRACT | FULL TEXT  

Neuroprotection and dopamine agonists
Schapira
Neurology 2002;58:S9-18.
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  

Tremor and dopamine agonists
Elble
Neurology 2002;58:S57-62.
ABSTRACT | FULL TEXT  

Treatment of early Parkinson's disease
Koller
Neurology 2002;58:S79-86.
ABSTRACT | FULL TEXT  

Excessive Daytime Sleepiness and Sudden-Onset Sleep in Parkinson Disease: A Survey by the Canadian Movement Disorders Group
Hobson et al.
JAMA 2002;287:455-463.
ABSTRACT | FULL TEXT  

Daytime Sleepiness, Agonist Therapy, and Driving in Parkinson Disease
Comella
JAMA 2002;287:509-511.
FULL TEXT  

Practice parameter: Initiation of treatment for Parkinson's disease: An evidence-based review: Report of the Quality Standards Subcommittee of the American Academy of Neurology
Miyasaki et al.
Neurology 2002;58:11-17.
ABSTRACT | FULL TEXT  

Ten-year follow-up of three different initial treatments in de-novo PD: A randomized trial
Lees et al.
Neurology 2001;57:1687-1694.
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  

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

Practice Parameter: neuroprotective strategies and alternative therapies for Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.
Suchowersky et al.
Neurology 2006;66:976-982.
ABSTRACT | FULL TEXT