Time course of loss of clinical benefit following withdrawal of levodopa/carbidopa and bromocriptine in early Parkinson's disease

Hauser, Robert A.; Koller, William C.; Hubble, Jean; Malapira, Teresita; Busenbark, Karen; Olanow, C. Warren

doi:10.1002/1531-8257(200005)15:3<485::aid-mds1010>3.0.co;2-f

Cited by 61 publications

(39 citation statements)

References 15 publications

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“…Indeed, levodopa washout studies suggest that benefits can persist for weeks to months. 182,241 Benefits observed with levodopa treatment could also relate to preventing decompensation as a result of the early administration of a symptomatic drug (see Figure 8). In any event, the clinical results certainly do not provide any evidence to suggest that levodopa is toxic or accelerates the development of disability in patients with PD.…”

Section: Apoptosismentioning

confidence: 80%

The scientific and clinical basis for the treatment of Parkinson disease (2009)

Olanow¹,

Stern²,

Sethi³

2009

Neurology

760

658

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Parkinson disease (PD) is an age-related neurodegenerative disorder that affects as many as 1-2% of persons aged 60 years and older. With the aging of the population, the frequency of PD is expected to increase dramatically in the coming decades. Current therapy is largely based on a dopamine replacement strategy, primarily using the dopamine precursor levodopa. However, chronic treatment is associated with the development of motor complications, and the disease is inexorably progressive. Further, advancing disease is associated with the emergence of features such as freezing, falling, and dementia which are not adequately controlled with dopaminergic therapies. Indeed, it is now appreciated that these nondopaminergic features are common and the major source of disability for patients with advanced disease. Many different therapeutic agents and treatment strategies have been evaluated over the past several years to try and address these unmet medical needs, and many promising approaches are currently being tested in the laboratory and in the clinic. As a result, there are now many new therapies and strategic approaches available for the treatment of the different stages of PD, with which the treating physician must be familiar in order to provide patients with optimal care. This monograph provides an overview of the management of PD patients, with an emphasis on pathophysiology, and the results of recent clinical trials. It is intended to provide physicians with an understanding of the different treatment options that are available for managing the different stages of the disease and the scientific rationale of the different approaches. 1 PD is the second most common neurodegenerative disorder, with an average age at onset of about 60 years. An estimated 5 million people throughout the world have PD, with 1 million individuals each in the United States and in Europe with the disorder. PD affects approximately 0.3% of the population and 1% to 2% of those older than 60 years.2 With the aging of the population and the substantial increase in the number of at-risk individuals older than 60 years, it is anticipated that the prevalence of PD will increase dramatically in the coming decades.

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Section: Apoptosismentioning

confidence: 80%

The scientific and clinical basis for the treatment of Parkinson disease (2009)

Olanow¹,

Stern²,

Sethi³

2009

Neurology

760

658

View full text Add to dashboard Cite

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“…However, there is no direct evidence to support the hypothesis that all levodopa effects will eventually be washed out. In contrast the close quantitative prediction of the observed effects based on the DATATOP cohort (13) and the study by Hauser et al (33) provide strong support for the observed ELLDOPA results being due to a combination of continuing protective effect and partial washout of symptomatic effect.…”

Section: Implications For Interpretation Of Elldopa Resultsmentioning

confidence: 99%

Levodopa Slows Progression of Parkinson’s Disease. External Validation by Clinical Trial Simulation

2007

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This simulation work confirmed the conclusion of the DATATOP analysis finding that levodopa slows disease progression. The simulation results also showed that a dose-related increased rate of progression in Parkinson's disease, obscured by symptomatic benefit, is very unlikely. Finally, the simulation results also shown that 2 weeks washout period was not adequate to completely eliminate the symptomatic benefits of levodopa.

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“…The long duration response to levodopa is more prominent in the earlier stages of Parkinson's disease and can last for several days. 39 Although the overnight 12 hour drug withdrawal in this study was sufficient to cause a significant increase in motor impairment (UPDRS), it may not have been sufficient to affect the motor component of response time, which did not differ from the control subjects.…”

Section: Discussionmentioning

confidence: 70%

Cognitive slowing in Parkinson's disease resolves after practice

Press

Mechanic²,

Tarsy³

et al. 2002

Journal of Neurology, Neurosurgery &Amp; Psychiatry

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Objective: To assess the effect of dopaminergic repletion on working memory in Parkinson's disease. Methods: The role of dopaminergic state on working memory in patients with Parkinson's disease was determined using the Sternberg item recognition paradigm, a continuous performance task that dissociates the motor and cognitive components of response time. Ten patients with Parkinson's disease were tested in an "on" state (on dopaminergic drug treatment) and a practical "off" state in two sessions held one week apart in counterbalanced order; 10 controls matched for age and education were studied at the same time points. Results: Patients with Parkinson's disease showed impaired working memory, independent of motor slowing. During session 1, the performance of the patients was worse than the controls, regardless of dopaminergic state. The patients showed a significant improvement in the cognitive component of task performance during the second session, such that they no longer differed from the controls. The performance of the control subjects remained stable over the two sessions. Conclusions: Working memory performance of patients with Parkinson's disease did not change in association with dopaminergic state; rather, the performance improved over time. The pattern of improvement over time suggests a delay in proceduralising the task, similar to the deficits shown by such patients in procedural learning of other tasks.

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Time course of loss of clinical benefit following withdrawal of levodopa/carbidopa and bromocriptine in early Parkinson's disease

Cited by 61 publications

References 15 publications

The scientific and clinical basis for the treatment of Parkinson disease (2009)

The scientific and clinical basis for the treatment of Parkinson disease (2009)

Levodopa Slows Progression of Parkinson’s Disease. External Validation by Clinical Trial Simulation

Cognitive slowing in Parkinson's disease resolves after practice

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