Pramipexole vs levodopa as initial treatment for Parkinson disease: A randomized controlled trial. Parkinson Study Group

JAMA. 2000 Oct 18;284(15):1931-8. doi: 10.1001/jama.284.15.1931.


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-beta-carboxymethoxy-3-beta-(4-iodophenyl)tropane (beta-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 beta-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. JAMA. 2000;284:1931-1938.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antiparkinson Agents / adverse effects
  • Antiparkinson Agents / pharmacology
  • Antiparkinson Agents / therapeutic use*
  • Benzothiazoles
  • Carrier Proteins / metabolism*
  • Cocaine / analogs & derivatives*
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / metabolism*
  • Dopamine / metabolism*
  • Dopamine Agents / adverse effects
  • Dopamine Agents / pharmacology
  • Dopamine Agents / therapeutic use*
  • Dopamine Agonists / pharmacology
  • Dopamine Agonists / therapeutic use
  • Dopamine Plasma Membrane Transport Proteins
  • Double-Blind Method
  • Dyskinesias
  • Female
  • Humans
  • Iodine Radioisotopes
  • Levodopa / adverse effects
  • Levodopa / pharmacology
  • Levodopa / therapeutic use*
  • Male
  • Membrane Glycoproteins*
  • Membrane Transport Proteins*
  • Middle Aged
  • Nerve Tissue Proteins / metabolism
  • Parkinson Disease / diagnosis
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / physiopathology
  • Pramipexole
  • Proportional Hazards Models
  • Quality of Life
  • Radiopharmaceuticals
  • Thiazoles / adverse effects
  • Thiazoles / pharmacology
  • Thiazoles / therapeutic use*
  • Tomography, Emission-Computed, Single-Photon


  • Antiparkinson Agents
  • Benzothiazoles
  • Carrier Proteins
  • Dopamine Agents
  • Dopamine Agonists
  • Dopamine Plasma Membrane Transport Proteins
  • Iodine Radioisotopes
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Radiopharmaceuticals
  • Thiazoles
  • Levodopa
  • 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane
  • Pramipexole
  • Cocaine
  • Dopamine