Topic
Levodopa
About: Levodopa is a research topic. Over the lifetime, 5253 publications have been published within this topic receiving 200631 citations.
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Papers
TL;DR: Patients experiencing complications, such as worsening symptoms and functional impairment when a medication dose wears off ("off periods"), medication-resistant tremor, and dyskinesias, benefit from advanced treatments such as therapy with levodopa-carbidopa enteral suspension or deep brain stimulation.
Abstract: Importance Parkinson disease is the most common form of parkinsonism, a group of neurological disorders with Parkinson disease–like movement problems such as rigidity, slowness, and tremor. More than 6 million individuals worldwide have Parkinson disease. Observations Diagnosis of Parkinson disease is based on history and examination. History can include prodromal features (eg, rapid eye movement sleep behavior disorder, hyposmia, constipation), characteristic movement difficulty (eg, tremor, stiffness, slowness), and psychological or cognitive problems (eg, cognitive decline, depression, anxiety). Examination typically demonstrates bradykinesia with tremor, rigidity, or both. Dopamine transporter single-photon emission computed tomography can improve the accuracy of diagnosis when the presence of parkinsonism is uncertain. Parkinson disease has multiple disease variants with different prognoses. Individuals with a diffuse malignant subtype (9%-16% of individuals with Parkinson disease) have prominent early motor and nonmotor symptoms, poor response to medication, and faster disease progression. Individuals with mild motor-predominant Parkinson disease (49%-53% of individuals with Parkinson disease) have mild symptoms, a good response to dopaminergic medications (eg, carbidopa-levodopa, dopamine agonists), and slower disease progression. Other individuals have an intermediate subtype. For all patients with Parkinson disease, treatment is symptomatic, focused on improvement in motor (eg, tremor, rigidity, bradykinesia) and nonmotor (eg, constipation, cognition, mood, sleep) signs and symptoms. No disease-modifying pharmacologic treatments are available. Dopamine-based therapies typically help initial motor symptoms. Nonmotor symptoms require nondopaminergic approaches (eg, selective serotonin reuptake inhibitors for psychiatric symptoms, cholinesterase inhibitors for cognition). Rehabilitative therapy and exercise complement pharmacologic treatments. Individuals experiencing complications, such as worsening symptoms and functional impairment when a medication dose wears off (“off periods”), medication-resistant tremor, and dyskinesias, benefit from advanced treatments such as therapy with levodopa-carbidopa enteral suspension or deep brain stimulation. Palliative care is part of Parkinson disease management. Conclusions and Relevance Parkinson disease is a heterogeneous disease with rapidly and slowly progressive forms. Treatment involves pharmacologic approaches (typically with levodopa preparations prescribed with or without other medications) and nonpharmacologic approaches (such as exercise and physical, occupational, and speech therapies). Approaches such as deep brain stimulation and treatment with levodopa-carbidopa enteral suspension can help individuals with medication-resistant tremor, worsening symptoms when the medication wears off, and dyskinesias.
2,039 citations
TL;DR: Electrical stimulation of the subthalamic nucleus is an effective treatment for advanced Parkinson's disease and the severity of symptoms off medication decreases, and the dose of levodopa can be reduced with consequent reduction in dyskinesias.
Abstract: Background In many patients with idiopathic Parkinson's disease, treatment with levodopa is complicated by fluctuations between an “off” period (also referred to as “off medication”), when the medication is not working and the motor symptoms of parkinsonism are present, and an “on” period, when the medication is causing improved mobility (also referred to as “on medication”), often accompanied by debilitating dyskinesias. In animal models of Parkinson's disease, there is overactivity in the subthalamic nucleus, and electrical stimulation of the subthalamic nucleus improves parkinsonism. We therefore sought to determine the efficacy and safety of electrical stimulation of the subthalamic nucleus in patients with Parkinson's disease. Methods We studied 24 patients with idiopathic Parkinson's disease in whom electrodes were implanted bilaterally in the subthalamic nucleus under stereotactic guidance with imaging and electrophysiologic testing of the location. Twenty were followed for at least 12 months. Clin...
2,005 citations
TL;DR: The clinical data suggest that levodopa either slows the progression of Parkinson's disease or has a prolonged effect on the symptoms of the disease, and the neuroimaging data suggest either thatlevodopa accelerates the loss of nigrostriatal dopamine nerve terminals or that its pharmacologic effects modify the dopamine transporter.
Abstract: background Despite the known benefit of levodopa in reducing the symptoms of Parkinson’s disease, concern has been expressed that its use might hasten neurodegeneration. This study assessed the effect of levodopa on the rate of progression of Parkinson’s disease. methods In this randomized, double-blind, placebo-controlled trial, we evaluated 361 patients with early Parkinson’s disease who were assigned to receive carbidopa–levodopa at a daily dose of 37.5 and 150 mg, 75 and 300 mg, or 150 and 600 mg, respectively, or a matching placebo for a period of 40 weeks, and then to undergo withdrawal of treatment for 2 weeks. The primary outcome was a change in scores on the Unified Parkinson’s Disease Rating Scale (UPDRS) between baseline and 42 weeks. Neuroimaging studies of 142 subjects were performed at baseline and at week 40 to assess striatal dopamine-transporter density with the use of iodine-123–labeled 2- b -carboxymethoxy3- b -(4-iodophenyl)tropane ([ 123 I] b -CIT) uptake. results The severity of parkinsonism increased more in the placebo group than in all the groups receiving levodopa: the mean difference between the total score on the UPDRS at baseline and at 42 weeks was 7.8 units in the placebo group, 1.9 units in the group receiving levodopa at a dose of 150 mg daily, 1.9 in those receiving 300 mg daily, and i1.4 in those receiving 600 mg daily (P<0.001). In contrast, in a substudy of 116 patients the mean percent decline in the [ 123 I] b -CIT uptake was significantly greater with levodopa than placebo (–6 percent among those receiving levodopa at 150 mg daily, –4 percent in those receiving it at 300 mg daily, and –7.2 percent among those receiving it at 600 mg daily, as compared with –1.4 percent among those receiving placebo; 19 patients with no dopaminergic deficits on the baseline scans were excluded from the analysis) (P=0.036). The subjects receiving the highest dose of levodopa had significantly more dyskinesia, hypertonia, infection, headache, and nausea than those receiving placebo. conclusions The clinical data suggest that levodopa either slows the progression of Parkinson’s disease or has a prolonged effect on the symptoms of the disease. In contrast, the neuroimaging data suggest either that levodopa accelerates the loss of nigrostriatal dopamine nerve terminals or that its pharmacologic effects modify the dopamine transporter. The potential long-term effects of levodopa on Parkinson’s disease remain uncertain.
1,810 citations
TL;DR: Early Parkinson's disease can be managed successfully for up to five years with a reduced risk of dyskinesia by initiating treatment with ropinirole alone and supplementing it with levodopa if necessary.
Abstract: Background There is debate about whether the initial treatment for patients with Parkinson's disease should be levodopa or a dopamine agonist. Methods In this prospective, randomized, double-blind study, we compared the safety and efficacy of the dopamine D2–receptor agonist ropinirole with that of levodopa over a period of five years in 268 patients with early Parkinson's disease. If symptoms were not adequately controlled by the assigned study medication, patients could receive supplementary levodopa, administered in an open-label fashion. The primary outcome measure was the occurrence of dyskinesia. Results Eighty-five of the 179 patients in the ropinirole group (47 percent) and 45 of the 89 patients in the levodopa group (51 percent) completed all five years of the study. In the ropinirole group, 29 of the 85 patients (34 percent) received no levodopa supplementation. The analysis of the time to dyskinesia showed a significant difference in favor of ropinirole (hazard ratio for remaining free of dyski...
1,631 citations
TL;DR: Evidence is provided that dopamine plays an important role in a specific cortical function in rhesus monkeys and that this role can be pharmacologically reversed with dopamine agonists.
Abstract: Depletion of dopamine in a circumscribed area of association cortex in rhesus monkeys produces an impairment in spatial delayed alternation performance nearly as severe as that caused by surgical ablation of the same area. This behavioral deficit can be pharmacologically reversed with dopamine agonists such as L-dopa and apomorphine. These data provide direct evidence that dopamine plays an important role in a specific cortical function.
1,620 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2026 | 1 |
| 2025 | 156 |
| 2024 | 241 |
| 2023 | 329 |
| 2022 | 543 |
| 2021 | 126 |