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.
To compare the development of dopaminergic motor complications after
initial treatment of early PD with pramipexole vs levodopa.
Multicenter, parallel-group, double-blind, randomized controlled trial.
Academic movement disorders clinics at 22 sites in the United States
Three hundred one patients with early PD who required dopaminergic therapy
to treat emerging disability, enrolled between October 1996 and August 1997.
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-β-carboxymethoxy-3-β-(4-iodophenyl)tropane (β-CIT) uptake
on single photon emission computed tomography imaging of the dopamine transporter.
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 β-CIT uptake compared with a 24.8% (14.4%)
decline in subjects treated initially with levodopa (n = 39; P = .15).
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.