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Updated: Aug 25, 2025
Induction and Assessment of Levodopa-induced Dyskinesias in a Rat Model of Parkinson's Disease
Published on: October 14, 2021
Levodopa Response in Patients With Early Parkinson Disease: Further Observations of the LEAP Study
Henrieke L Frequin1, Jason Schouten1, Constant V M Verschuur1
1From the Department of Neurology (H.L.F., J.S., C.V.M.V., S.R.S., J.M.D., R.M.A.d.B.) and Department of Medical Psychology (J.A.B.), Amsterdam University Medical Centers; Radboud University Medical Center (B.P., B.R.B.), Department of Neurology; Leiden University Medical Center (J.J.H.), Department of Neurology; University Medical Center Groningen (T.L.), Department of Neurology; Zuyderland Medical Center (G.T.), Department of Neurology; Excellent Klinieken (A.G.M.), Dordrecht, Department of Neurology; University Medical Center Schleswig-Holstein (G.D.), Department of Neurology; Toronto Western Hospital (A.L.), University of Toronto, Department of Neurology; Amsterdam University Medical Centers (M.G.W.D.), Department of Epidemiology and Data Science; and Amsterdam University Medical Centers (R.J.H.), Clinical Research Unit.
Background And Objectives:
The Levodopa in EArly Parkinson's Disease (LEAP) study enabled us to conduct post hoc analyses concerning the effects of levodopa in patients with early Parkinson disease.
Methods:
The LEAP study was a double-blind, placebo-controlled, randomized, delayed-start trial in which patients with early Parkinson disease were randomized to receive levodopa/carbidopa 300/75 mg daily for 80 weeks (early-start group) or to placebo for 40 weeks followed by levodopa/carbidopa 300/75 mg daily for 40 weeks (delayed-start group). We analyzed the effect of levodopa with the Unified Parkinson's Disease Rating Scale on bradykinesia, rigidity, and tremor. At week 80, participants answered 3 questions regarding motor response fluctuations.
Results:
A total of 222 patients were randomized to the early-start group (mean ± SD age at baseline 64.8 ± 8.7 years; 71% male) and 223 to the delayed-start group (mean ± SD age at baseline 65.5 ± 8.8 years; 69% male). The difference between the early- and delayed-start groups in mean change from baseline to week 4, expressed as Hedges g effect size, was -0.33 for bradykinesia, -0.29 for rigidity, and -0.25 for tremor (for all symptoms indicating a small effect in favor of the early-start group); from baseline to week 22, respectively, -0.49, -0.36, and -0.44 (small to medium effect); and from baseline to week 40, respectively, -0.32, -0.19, and -0.27 (small effect). At 80 weeks, fewer patients in the early-start group (46 of 205 patients, 23%) experienced motor response fluctuations than patients in the delayed-start group (81 of 211, 38%; p < 0.01).
Discussion:
In patients with early Parkinson disease, levodopa improves bradykinesia, rigidity, and tremor to the same order of magnitude. For all 3 symptoms, effects were larger at 22 weeks compared with 4 weeks. At 80 weeks, there were fewer patients with motor response fluctuations in the group that had started levodopa earlier.
Classification Of Evidence:
This study provides Class II evidence that the effect of levodopa on bradykinesia, rigidity, and tremor is larger after 22 weeks compared with 4 weeks of treatment.
Trial Registration Information:
ISRCTN30518857, EudraCT number 2011-000678-72.
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