Levodopa-Induced Response Fluctuations in Patients with Parkinson???s Disease: Strategies for Management

van Laar, Teus

doi:10.2165/00023210-200317070-00002

Cited by 43Parkinson's Disease Mechanisms and TreatmentsNeurological disorders and treatmentsNeurotransmitter Receptor Influence on Behavior

Levodopa-Induced Response Fluctuations in Patients with Parkinson???s Disease: Strategies for Management

van Laar, Teus·2003·CNS Drugs

DOI 10.2165/00023210-200317070-00002

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Abstract

Fluctuations in response to levodopa in patients in the advanced stages of idiopathic Parkinson's disease occur frequently and are a difficult problem to treat. Patients who are treated with levodopa have an additional 10% risk of experiencing response fluctuations with each year of treatment: 50% of patients have this problem after 5 years of receiving levodopa therapy and almost 100% of patients after 10 years. The mechanisms by which response fluctuations occur are only partially understood and can be divided into three main types: (i) presynaptic neuronal degeneration leading to a lack of buffering of released levodopa, which is mainly related to wearing-off phenomena; (ii) postsynaptic changes in dopamine receptor sensitivity and number, partially caused by the presynaptic changes, which are clinically related to at-random response fluctuations; and (iii) pharmacokinetic and pharmacodynamic influences of exogenously administered dopaminergic agents. Several oral and parenteral treatment strategies are recommended to manage response fluctuations, such as optimisation of dopamine receptor agonist therapy in combination with a reduction of the levodopa load; use of slow-release levodopa formulations; use of catechol-O-methyltransferase inhibitors; an increase of levodopa dose frequency; use of high-dose amantadine; and intermittent or continuous use of apomorphine and/or levodopa. Continuous stimulation of dopamine receptors with dopaminergic agents is one of the crucial basic steps in the treatment of patients at an advanced stage of Parkinson's disease, and the preferential use of dopamine receptor agonists has proven to be successful in the prevention and treatment of response fluctuations.

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As Parkinson's disease progresses, increasing dopaminergic medication becomes insufficient and complicated because of the increased occurrence of dyskinesias.
“As the disease progresses, increasing dopaminergic medication (both frequency and dosage) becomes insufficient and complicated because of the increased occurrence of dyskinesias [17].”
From BEWARE: Body awareness training in the treatment of wearing-off related anxiety in patients with Parkinson's disease: study protocol for a randomized controlled trial. (2015) · cites this paper as [17]
Wearing-off is an inevitable and disabling consequence of long-term dopamine replacement therapy in patients with Parkinson's disease.
“Wearing-off is an inevitable and disabling consequence of long-term DRT in patients with PD”
From BEWARE: Body awareness training in the treatment of wearing-off related anxiety in patients with Parkinson's disease: study protocol for a randomized controlled trial. (2015) · cites this paper as [17]
The development of wearing-off is associated with long-term treatment of Parkinson's disease with dopamine replacement therapy as well as with an early onset of disease, longer disease duration, and higher doses of levodopa.
“Because the development of wearing-off is associated with long-term treatment of PD with DRT as well as with an early onset of disease, longer disease duration, and higher doses of levodopa [5, 17, 51]”
From BEWARE: Body awareness training in the treatment of wearing-off related anxiety in patients with Parkinson's disease: study protocol for a randomized controlled trial. (2015) · cites this paper as [17]
Random fluctuations appear more difficult to treat with pharmacotherapeutic approaches because they are unpredictable and not directly related to a lower level of dopamine.
“Also, random fluctuations appear to be more difficult to treat with pharmacotherapeutic approaches because they are unpredictable and not directly related to a lower level of dopamine [17].”
From BEWARE: Body awareness training in the treatment of wearing-off related anxiety in patients with Parkinson's disease: study protocol for a randomized controlled trial. (2015) · cites this paper as [17]

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Authors: van Laar, T.
Venue: CNS Drugs
Publisher: Springer Science and Business Media LLC
Published: 2003
Volume: 17
Issue: 7
Pages: 475-489
ISSN: 1172-7047 (ISSN-L)
DOI: 10.2165/00023210-200317070-00002
OpenAlex: W2136886620
Cited by: 43
References: 93
Citations by year: 2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 1 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 2 · 2014: 3 · 2012: 1
FWCI: 1.94
Type: journal article
Language: en
Open access: closed
Locations: CNS Drugs (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
Health Sciences › Medicine › Neurology › Neurological disorders and treatments
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords: Parkinson's disease, wearing-off phenomenon, dopamine receptor sensitivity, dopamine agonists, catechol-O-methyltransferase inhibitors, amantadine, apomorphine, advanced Parkinson's disease
MeSH terms: Age Factors, Antiparkinson Agents, Delayed-Action Preparations, Dose-Response Relationship, Drug, Humans, Levodopa, Motor Activity, Movement Disorders, Parkinson Disease, Time Factors, Treatment Outcome

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Levodopa-Induced Response Fluctuations in Patients with Parkinson???s Disease: Strategies for Management

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