Effects of caffeine on levodopa pharmacokinetics and pharmacodynamics in Parkinson disease

Deleu, Dirk; Jacob, Peyton; Chand, Priyabrata; Sarre, Sophie; Colwell, Arthur R.

doi:10.1212/01.wnl.0000233916.57415.9d

Cited by 34 publications

(26 citation statements)

References 9 publications

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“…25,26 Numerous animal studies have found motor improvement in toxin-induced models of PD, 27 in dopamine-deficient mice, 28 and in drug-induced parkinsonism 29 with caffeine. Caffeine may also increase bioavailability and prolong the clinical effect of levodopa 30 (note that the clinical effect of caffeine may persist even after levodopa levels decline, suggesting that the D2 receptor interactions are also important). Two early smallscale human studies evaluated caffeine as a potential symptomatic agent in PD, and found no effect.…”

Section: Caffeine and Edsmentioning

confidence: 99%

Caffeine for treatment of Parkinson disease

et al. 2012

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Objective: Epidemiologic studies consistently link caffeine, a nonselective adenosine antagonist, to lower risk of Parkinson disease (PD). However, the symptomatic effects of caffeine in PD have not been adequately evaluated. Methods:We conducted a 6-week randomized controlled trial of caffeine in PD to assess effects upon daytime somnolence, motor severity, and other nonmotor features. Patients with PD with daytime somnolence (Epworth Ͼ10) were given caffeine 100 mg twice daily ϫ3 weeks, then 200 mg twice daily ϫ3 weeks, or matching placebo. The primary outcome was the Epworth Sleepiness Scale score. Secondary outcomes included motor severity, sleep markers, fatigue, depression, and quality of life. Effects of caffeine were analyzed with Bayesian hierarchical models, adjusting for study site, baseline scores, age, and sex.Results: Of 61 patients, 31 were randomized to placebo and 30 to caffeine. On the primary intention-to-treat analysis, caffeine resulted in a nonsignificant reduction in Epworth Sleepiness Scale score (Ϫ1.71 points; 95% confidence interval [CI] Ϫ3.57, 0.13). However, somnolence improved on the Clinical Global Impression of Change (ϩ0.64; 0.16, 1.13, intention-to-treat), with significant reduction in Epworth Sleepiness Scale score on per-protocol analysis (Ϫ1.97; Ϫ3.87, Ϫ0.05). Caffeine reduced the total Unified Parkinson's Disease Rating Scale score (Ϫ4.69 points; Ϫ7.7, Ϫ1.6) and the objective motor component (Ϫ3.15 points; Ϫ5.50, Ϫ0.83).Other than modest improvement in global health measures, there were no changes in quality of life, depression, or sleep quality. Adverse events were comparable in caffeine and placebo groups. Conclusions:Caffeine provided only equivocal borderline improvement in excessive somnolence in PD, but improved objective motor measures. These potential motor benefits suggest that a larger long-term trial of caffeine is warranted.

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Section: Caffeine and Edsmentioning

confidence: 99%

Caffeine for treatment of Parkinson disease

et al. 2012

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“…Moreover, the beneficial effects of caffeine in Parkinson's disease patients was also reported [66]. Furthermore, caffeine administered before levodopa may improve its pharmacokinetics in some patients with Parkinson's disease [67].…”

Section: Parkinson's Diseasementioning

confidence: 89%

Caffeine and Adenosine

Ribeiro

Sebastião

2010

JAD

407

243

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Abstract. Caffeine causes most of its biological effects via antagonizing all types of adenosine receptors (ARs): A1, A2A, A3, and A2B and, as does adenosine, exerts effects on neurons and glial cells of all brain areas. In consequence, caffeine, when acting as an AR antagonist, is doing the opposite of activation of adenosine receptors due to removal of endogenous adenosinergic tonus. Besides AR antagonism, xanthines, including caffeine, have other biological actions: they inhibit phosphodiesterases (PDEs) (e.g., PDE1, PDE4, PDE5), promote calcium release from intracellular stores, and interfere with GABA-A receptors. Caffeine, through antagonism of ARs, affects brain functions such as sleep, cognition, learning, and memory, and modifies brain dysfunctions and diseases: Alzheimer's disease, Parkinson's disease, Huntington's disease, Epilepsy, Pain/Migraine, Depression, Schizophrenia. In conclusion, targeting approaches that involve ARs will enhance the possibilities to correct brain dysfunctions, via the universally consumed substance that is caffeine.

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“…Caffeine may shorten the time to maximum concentration and increase the magnitude of the response. 253 To tailor therapy to an individual patient, the clinician should be aware of the magnitude and duration of the motor response after a dose of levodopa/ carbidopa, and the relationship between "on" and "off " periods and dyskinesias. This can sometimes be determined from the patient history but occasionally may require monitoring of the patient during several dosing cycles.…”

Section: 242mentioning

confidence: 99%

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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Effects of caffeine on levodopa pharmacokinetics and pharmacodynamics in Parkinson disease

Cited by 34 publications

References 9 publications

Caffeine for treatment of Parkinson disease

Caffeine for treatment of Parkinson disease

Caffeine and Adenosine

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

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