Long term motor complications of levodopa: clinical features, mechanisms, and management strategies
Open accessAbstract
Levodopa is the most effective symptomatic treatment of Parkinson’s disease. However, after an initial period of dramatic benefit, several limitations become apparent including, “dopa resistant” motor symptoms (postural abnormalities, freezing episodes, speech impairment), “dopa resistant” non-motor signs (autonomic dysfunction, mood and cognitive impairment, etc), and/or drug related side effects (especially psychosis, motor fluctuations, and dyskinesias). Motor complications include fluctuations, dyskinesias, and dystonias. They can be very disabling and difficult to treat. Therefore, strategies should ideally be developed to prevent them. Though mechanisms underlying motor complications are only partially understood, recent work has revealed the importance of pulsatile stimulation of postsynaptic dopamine receptors and the disease severity. As a result of intermittent stimulation there occurs a cascade of changes in cell signalling leading to upregulation of the N-methyl-D-aspartate subtype of gamma-aminobutryric acid-ergic neurones. Modified preparations of levodopa (controlled release preparations, liquid levodopa), catecholamine-o-methyltransferase inhibitors, dopamine agonists, amantidine, and various neurosurgical approaches have been used in the prevention and/or treatment of motor complications. Current management of motor complications is less than satisfactory. With better understanding of the pathogenetic mechanisms, it is hoped that future therapeutic strategies will provide a safer and targeted treatment.
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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 [5]
The Clinical Aspects section (page unavailable) links chronic levodopa use and young-onset Parkinson's disease to motor complications, and describes wearing-off as emerging with disease progression. The copy does not specifically identify higher levodopa doses as a risk factor for developing wearing-off; its young-onset statement also concerns motor complications generally rather than wearing-off specifically. (LLM, conf=0.85)
Experimental — accuracy not yet measuredWearing-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 [5]
The Clinical Aspects and Metabolism sections describe wearing-off as a motor complication that can emerge as Parkinson’s disease progresses during levodopa treatment. The Abstract says long-term motor complications are common and can be disabling, but the paper does not establish that wearing-off itself is inevitable for every patient receiving dopamine replacement therapy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredWearing-off is related to longer disease duration.
“and is related to longer disease duration [5]”
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“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], we will inadvertently include patients who are in a more advanced stage of the disease.”
Background
- Authors
- Thanvi, B. R., & Lo, T. C. N.
- Affiliations
- Leicester Royal Infirmary (GB)
- Leicester General Hospital (GB)
- Corresponding author
- Thanvi, B R
- Venue
- Postgraduate Medical Journal
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-08
- Volume
- 80
- Issue
- 946
- Pages
- 452-458
- ISSN
- 0032-5473 (ISSN-L)
- 1469-0756
- PMC
- PMC1743071
- OpenAlex
- W2106983119
- Cited by
- 194
- References
- 54
- Citations by year
- 2026: 8 · 2025: 20 · 2024: 9 · 2023: 22 · 2022: 17 · 2021: 21 · 2020: 20 · 2019: 9 · 2018: 7 · 2017: 7 · 2016: 7 · 2015: 9 · 2014: 5 · 2013: 1 · 2012: 1
- FWCI
- 0.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Postgraduate Medical Journal (publishedVersion)
- PubMed Central (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
- levodopa, Parkinson's disease, motor complications, dyskinesia, motor fluctuations, freezing of gait, dopamine agonists, amantadine, dystonia, autonomic dysfunction
- MeSH terms
- Antiparkinson Agents, Dyskinesia, Drug-Induced, Dystonia, Forecasting, Humans, Levodopa, Parkinson Disease
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