Caffeine for treatment of Parkinson disease
A randomized controlled trial
This article has been corrected.
VIEW CORRECTION
Abstract
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 >10) were given caffeine 100 mg twice daily ×3 weeks, then 200 mg twice daily ×3 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 (−1.71 points; 95% confidence interval [CI] −3.57, 0.13). However, somnolence improved on the Clinical Global Impression of Change (+0.64; 0.16, 1.13, intention-to-treat), with significant reduction in Epworth Sleepiness Scale score on per-protocol analysis (−1.97; −3.87, −0.05). Caffeine reduced the total Unified Parkinson's Disease Rating Scale score (−4.69 points; −7.7, −1.6) and the objective motor component (−3.15 points; −5.50, −0.83). 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.
Classification of evidence:
This study provides Class I evidence that caffeine, up to 200 mg BID for 6 weeks, had no significant benefit on excessive daytime sleepiness in patients with PD.
Get full access to this article
View all available purchase options and get full access to this article.
Supplementary Material
REFERENCES
1.
Hernan MA, Takkouche B, Caamano-Isorna F, Gestal-Otero JJ. A meta-analysis of coffee drinking, cigarette smoking, and the risk of Parkinson's disease. Ann Neurol 2002; 52: 276– 284 .
2.
Altman RD, Lang AE, Postuma RB. Caffeine in Parkinson's disease: a pilot open-label, dose-escalation study. Mov Disord 2011; 26: 2427– 2431 .
3.
Kitagawa M, Houzen H, Tashiro K. Effects of caffeine on the freezing of gait in Parkinson's disease. Mov Disord 2007; 22: 710– 712 .
4.
Schwarzschild MA, Chen JF, Ascherio A. Caffeinated clues and the promise of adenosine A(2A) antagonists in PD. Neurology 2002; 58: 1154– 1160 .
5.
Xu K, Bastia E, Schwarzschild M. Therapeutic potential of adenosine A(2A) receptor antagonists in Parkinson's disease. Pharmacol Ther 2005; 105: 267– 310 .
6.
Factor S, Mark MH, Watts R, Struck L, et al. A long-term study of istradefylline in subjects with fluctuating Parkinson's disease. Parkinsonism Relat Disord 2010; 16: 423– 426 .
7.
Hauser RA, Cantillon M, Pourcher E, et al. Preladenant in patients with Parkinson's disease and motor fluctuations: a phase 2, double-blind, randomised trial. Lancet Neurol 2011; 10: 221– 229 .
8.
Johns MW. A new method for measuring daytime sleepiness: the Epworth Sleepiness Scale. Sleep 1991; 14: 540– 545 .
9.
Barone JJ, Roberts HR. Caffeine consumption. Food Chem Toxicol 1996; 34: 119– 129 .
10.
Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression. Arch Gen Psychiatry 1961; 4: 561– 571 .
11.
Nawrot P, Jordan S, Eastwood J, Rotstein J, Hugenholtz A, Feeley M. Effects of caffeine on human health. Food Addit Contam 2003; 20: 1– 30 .
12.
Merino-Andreu M, Arnulf I, Konofal E, Derenne JP, Agid Y. Unawareness of naps in Parkinson's disease and in disorders with excessive daytime sleepiness. Neurology 2003; 60: 1553– 1554 .
13.
Hogl B, Saletu M, Brandauer E, et al. Modafinil for the treatment of daytime sleepiness in Parkinson's disease: a double-blind, randomized, crossover, placebo-controlled polygraphic trial. Sleep 2002; 25: 905– 909 .
14.
Adler CH, Caviness JN, Hentz JG, Lind M, Tiede J. Randomized trial of modafinil for treating subjective daytime sleepiness in patients with Parkinson's disease. Mov Disord 2003; 18: 287– 293 .
15.
Ondo WG, Fayle R, Atassi F, Jankovic J. Modafinil for daytime somnolence in Parkinson's disease: double blind, placebo controlled parallel trial. J Neurol Neurosurg Psychiatry 2005; 76: 1636– 1639 .
16.
Fahn S, Elton R, members of the UDC. The Unified Parkinson's Disease Rating Scale. In:, Fahn S, Marsden CD, Calne D, Goldstein M, eds. Recent Developments in Parkinson's Disease. Florham Park, NJ: MacMillan HealthCare Information; 1987:153–163.
17.
Guy W. ECDEU Assessment Manual for Psychopharmacology: Revised: US Department of Health, Education, and Welfare, Public Health Service, Alcohol, Drug Abuse, and Mental Health Administration. NIMH Psychopharmacology Research Branch, Division of Extramural Research Programs; 1976:218– 222.
18.
Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD. The Fatigue Severity Scale: application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol 1989; 46: 1121– 1123 .
19.
Buysse DJ, Reynolds CF III, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res 1989; 28: 193– 213 .
20.
Peto V, Jenkinson C, Fitzpatrick R. PDQ-39: a review of the development, validation and application of a Parkinson's disease quality of life questionnaire and its associated measures. J Neurol 1998; 245 (suppl 1): S10– S14 .
21.
Ware JE, Sherbourne CD. The MOS 36-item Short Form health survey (SF-36): I: conceptual framework and item selection. Med Care 1992; 30: 473– 483 .
22.
Hagell P, Broman JE. Measurement properties and hierarchical item structure of the Epworth Sleepiness Scale in Parkinson's disease. J Sleep Res 2007; 16: 102– 109 .
23.
Razmy A, Lang AE, Shapiro CM. Predictors of impaired daytime sleep and wakefulness in patients with Parkinson disease treated with older (ergot) vs newer (nonergot) dopamine agonists. Arch Neurol 2004; 61: 97– 102 .
24.
Jenner P. Istradefylline, a novel adenosine A2A receptor antagonist, for the treatment of Parkinson's disease. Expert Opin Investig Drugs 2005; 14: 729– 738 .
25.
Benarroch EE. Adenosine and its receptors: multiple modulatory functions and potential therapeutic targets for neurologic disease. Neurology 2008; 70: 231– 236 .
26.
Fredholm BB, Svenningsson P. Adenosine-dopamine interactions: development of a concept and some comments on therapeutic possibilities. Neurology 2003; 61 (11 suppl 6): S5– S9 .
27.
Yu L, Schwarzschild MA, Chen JF. Cross-sensitization between caffeine- and L-dopa-induced behaviors in hemiparkinsonian mice. Neurosci Lett 2006; 393: 31– 35 .
28.
Kim DS, Palmiter RD. Adenosine receptor blockade reverses hypophagia and enhances locomotor activity of dopamine-deficient mice. Proc Natl Acad Sci USA 2003; 100: 1346– 1351 .
29.
Moo-Puc RE, Gongora-Alfaro JL, Alvarez-Cervera FJ, Pineda JC, Rankowsky-Sandoval G, Heredia-Lopez F. Caffeine and muscarinic antagonists act in synergy to inhibit haloperidol-induced catalepsy. Neuropharmacology 2003; 45: 493– 503 .
30.
Deleu D, Jacob P, Chand P, Sarre S, Colwell A. Effects of caffeine on levodopa pharmacokinetics and pharmacodynamics in Parkinson disease. Neurology 2006; 67: 897– 899 .
31.
Kartzinel R, Shoulson I, Calne DB. Studies with bromocriptine: III. Concomitant administration of caffeine to patients with idiopathic parkinsonism. Neurology 1976; 26: 741– 743 .
32.
Shoulson I, Chase T. Caffeine and the antiparkinsonian response to levodopa or piribedil. Neurology 1975; 25: 722– 724 .
33.
Fernandez HH, Greeley DR, Zweig RM, Wojcieszek J, Mori A, Sussman NM. Istradefylline as monotherapy for Parkinson disease: results of the 6002-US-051 trial. Parkinsonism Relat Disord 2010; 16: 16– 20 .
34.
Mizuno Y, Hasegawa K, Kondo T, Kuno S, Yamamoto M. Clinical efficacy of istradefylline (KW-6002) in Parkinson's disease: a randomized, controlled study. Mov Disord 2010; 25: 1437– 1443 .
35.
de Lau LM, Breteler MM. Epidemiology of Parkinson's disease. Lancet Neurol 2006; 5: 525– 535 .
36.
Tan EK, Chua E, Fook-Chong SM, et al. Association between caffeine intake and risk of Parkinson's disease among fast and slow metabolizers. Pharmacogenet Genomics 2007; 17: 1001– 1005 .
37.
Ascherio A, Chen H. Caffeinated clues from epidemiology of Parkinson's disease. Neurology 2003; 61 (11 suppl 6): S51– S54 .
38.
Poewe W, Mahlknecht P. The clinical progression of Parkinson's disease. Parkinsonism Relat Disord 2009; 15 (suppl 4): S28– S32 .
39.
Schapira AH, Obeso J. Timing of treatment initiation in Parkinson's disease: a need for reappraisal? Ann Neurol 2006; 59: 559– 562 .
Information & Authors
Information
Published In
Copyright
Copyright © 2012 by AAN Enterprises, Inc.
Publication History
Received: November 10, 2011
Accepted: January 25, 2012
Published online: August 1, 2012
Published in print: August 14, 2012
Disclosure
The authors report no disclosures relevant to the manuscript. Go to Neurology.org for full disclosures.
Authors
Author Contributions
R.B. Postuma was responsible for study concept, obtaining funding, acquisition of data, analysis and interpretation of data, and drafting of the manuscript. A.E. Lang was responsible for obtaining funding, acquisition of data, interpretation of data, and manuscript revision. Renato Munhoz was responsible for acquisition of data, interpretation of data, and manuscript revision. Katia Charland was responsible for statistical analysis and manuscript revision. Amelie Pelletier was responsible for generation of data, interpretation of data, and manuscript revision. Mariana Moscovich was responsible for acquisition of data and manuscript revision. Luciane Filla was responsible for acquisition of data and manuscript revision. Debora Zanatta was responsible for statistical assistance, interpretation of data, and manuscript revision. Silvia Rios-Romenets was responsible for acquisition of data and manuscript revision. Robert Altman was responsible for acquisition of data and manuscript revision. Rosa Chuang was responsible for acquisition of data and manuscript revision. Binit Shah was responsible for acquisition of data and manuscript revision.
Metrics & Citations
Metrics
Citations
Download Citations
If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Select your manager software from the list below and click Download.
Cited By
- Therapeutic Potential of Natural Compounds in Neurodegenerative Diseases: Insights from Clinical Trials, Pharmaceutics, 15, 1, (212), (2023).https://doi.org/10.3390/pharmaceutics15010212
- The Potential of Spent Coffee Grounds in Functional Food Development, Nutrients, 15, 4, (994), (2023).https://doi.org/10.3390/nu15040994
- Neurological Insights into Sleep Disorders in Parkinson’s Disease, Brain Sciences, 13, 8, (1202), (2023).https://doi.org/10.3390/brainsci13081202
- Therapeutic Potential of Heterocyclic Compounds Targeting Mitochondrial Calcium Homeostasis and Signaling in Alzheimer’s Disease and Parkinson’s Disease, Antioxidants, 12, 6, (1282), (2023).https://doi.org/10.3390/antiox12061282
- Daytime sleepiness in Parkinson's disease: a multifaceted symptom, Frontiers in Sleep, 2, (2023).https://doi.org/10.3389/frsle.2023.1302021
- Physical Exercise as a Potential Treatment for Fatigue in Parkinson’s Disease? A Systematic Review and Meta-Analysis of Pharmacological and Non-Pharmacological Interventions, Journal of Parkinson's Disease, 13, 5, (659-679), (2023).https://doi.org/10.3233/JPD-225116
- Should patients with Parkinson’s disease only visit a neurologist’s office? - a narrative review of neuropsychiatric disorders among people with Parkinson’s disease, Current Problems of Psychiatry, 23, 4, (220-236), (2023).https://doi.org/10.2478/cpp-2022-0021
- An Update on Nondopaminergic Treatments for Motor and Non-motor Symptoms of Parkinson’s Disease, Current Neuropharmacology, 21, 8, (1806-1826), (2023).https://doi.org/10.2174/1570159X20666220222150811
- ALSUntangled #70: caffeine, Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 24, 7-8, (766-770), (2023).https://doi.org/10.1080/21678421.2023.2220742
- The role of istradefylline in the Parkinson’s disease armamentarium, Expert Opinion on Pharmacotherapy, 24, 7, (863-871), (2023).https://doi.org/10.1080/14656566.2023.2201374
- See more
Loading...
View Options
Get Access
Login options
Check if you have access through your login credentials or your institution to get full access on this article.
Personal login Institutional LoginPurchase Options
Purchase this article to get full access to it.