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

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.