Dataset Information

Oral Levodopa Formulation Does Not Affect Progression of Parkinson Disease.

ABSTRACT:

Objective

Motor fluctuations develop in most patients treated with carbidopa/levodopa for Parkinson disease. The continuous dopamine stimulation hypothesis suggests that longer-acting forms of levodopa might improve outcomes, but this has been inadequately tested in humans. We undertook to determine if there is any difference in symptom progression rate among patients taking immediate-release carbidopa/levodopa (IR), controlled-release carbidopa/levodopa (CR), or carbidopa/levodopa/entacapone (CLE) using standard outcome measures in a naturalistic study.

Methods

We evaluated Parkinson disease subjects prospectively followed for up to 48 months in the Parkinson's Disease Biomarker Project. Bayesian linear or generalized linear mixed-effects models were developed to determine if oral levodopa formulation influenced the rate of symptom progression as measured by 8 outcome measures.

Results

At baseline, the IR, CR, and CLE groups were similar except that the CR group had milder disease and was represented at only 1 site, and the CLE group had a longer disease duration. In the primary analysis, there was no difference in rate of symptom progression as measured by the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale Part II, Part IV, or total score. In the secondary exploratory analysis, there was no difference in progression rate as measured by change in levodopa equivalent daily dose, Montreal Cognitive Assessment, Parkinson's Disease Questionnaire mobility subscore, Schwab and England Activities of Daily Living Scale, or a global composite outcome.

Conclusions

We found no difference in symptom progression rate in patients taking IR, CR, or CLE. This clinical observation supports pharmacokinetic studies demonstrating that none of these oral levodopa formulations achieve continuous dopamine stimulation.

SUBMITTER: Sethi A

PROVIDER: S-EPMC8283796 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Treatment of Parkinson disease commonly includes levodopa and dopamine agonists; however, the interaction of these 2 drugs is poorly understood.To examine the effects of a dopamine agonist on the motor response to levodopa.Double-blind, randomized, placebo-controlled, crossover clinical trial.Ambulatory academic referral center. Patients Thirteen patients with idiopathic Parkinson disease taking levodopa and experiencing motor fluctuations and dyskinesia.Eligible individuals were randomly assigned to receive pramipexole dihydrochloride or placebo for 4 weeks followed by a 2-hour intravenous levodopa infusion on consecutive days at 2 rates and with blinded assessments. They were then crossed over to the alternate oral therapy for 4 weeks followed by levodopa infusion and reassessment.Change in finger-tapping speed, measured using the area under the curve (AUC) for finger taps per minute across time; peak finger-tapping speed; duration of response; time to "ON" (defined as a 10% increase in finger-tapping speed above baseline); walking speed; and dyskinesia AUC.Pramipexole with levodopa infusion increased finger-tapping speed beyond the change in baseline by a mean (SE) of 170 (47.2) per minute x minutes (P = .006) and more than doubled the AUC for finger-tapping speed. Pramipexole increased peak finger-tapping speed by a mean (SE) of 18 (8.5) taps per minute (P = .02) and improved mean (SE) walking speed (15.9 [0.70] vs 18.9 [0.70] seconds, P = .004). Pramipexole prolonged duration of response after levodopa infusion and shortened time to ON. Pramipexole increased mean (SE) baseline dyskinesia scores (26.0 [5.85] vs 12.1 [5.85] points, P = .05) and peak dyskinesia scores with levodopa infusion.Pramipexole augmented the motor response to levodopa beyond a simple additive effect and increased the severity of levodopa-induced dyskinesia. When considering a combination of these therapies, an appropriate balance should be maintained regarding gain of motor function vs worsening of dyskinesia. Trial Registration clinicaltrials.gov Identifier: NCT00666653.