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Effect of exogenous melatonin on sleep and motor dysfunction in Parkinson's disease

A randomized, double blind, placebo-controlled study

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Abstract

Insomnia, sleep fragmentation and excessive daytime sleepiness are common in Parkinson's disease (PD) and may contribute to the reduction of cognition and alertness in those patients. Melatonin has been shown to improve sleep in several conditions. In experimental models of PD, melatonin can ameliorate motor symptoms. To evaluate the effect of melatonin on sleep and motor dysfuntion in PD, we studied 18 patients (Hoehn & Yahr I to III) from a PD clinic. Prior to treatment, motor dysfunction was assessed by UPDRS II, III and IV. Subjective sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI) and daytime somnolence by the Epworth Sleepiness Scale (ESS). Full polysomnography (PSG) was performed in all subjects. Patients were then randomized to receive melatonin (3mg) or placebo one hour before bedtime for four weeks. All measures were repeated at the end of treatment. On initial assessment, 14 patients (70%) showed poor quality sleep (PSQI > 6) and eight (40%) excessive daytime sleepiness (ESS > 10). Increased sleep latency (50%), REM sleep without atonia (66%), and reduced sleep efficiency (72%) were found on PSG. Eight patients had an apnea/ hipopnea index greater than 15 but no severe oxygen desaturation was observed. Sleep fragmentation tended to be more severe in patients on lower doses of levodopa (p = 0.07). Although melatonin significantly improved subjective quality of sleep (p = 0.03) as evaluated by the PSQI index, PSG abnormalities were not changed. Motor dysfunction was not improved by the use of melatonin. Undetected differences in motor scores and PSG findings may have been due to a small sample size and a type II error.

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References

  1. Larsen JP, Tandberg E (2001) Sleep disorders in patients with Parkinson's disease: epidemiology and management. CNS Drugs 15:267–275

    Article  PubMed  CAS  Google Scholar 

  2. Clarenbach P (2000) Parkinson's disease and sleep. J. Neurol 247:20–2

    Article  Google Scholar 

  3. Arnulf I (2005) Excessive daytime sleepiness in parkinsonism. Sleep Med 9:185–200

    Article  Google Scholar 

  4. Hebert M, Martin SK, Lee C, Eastman CA (2002) The effects of prior light history on the suppression of melatonin by light in humans. J Pineal Res 33:198–203

    Article  PubMed  CAS  Google Scholar 

  5. Dijk DJ, Lockley SW (2002) Integration of human sleep-wake regulation and circadian rhythmicity. J Appl Physiol 92:852–862

    PubMed  Google Scholar 

  6. Cagnacci A (1996) Melatonin in elation to physiology in adult humans. J Pineal Res 21:200–213

    Article  PubMed  CAS  Google Scholar 

  7. Arendt J, Skene DJ (2005) Melatonin as a chronobiotic. Sleep Med Rev 9:25–39

    Article  PubMed  Google Scholar 

  8. Pandi-Perumal SR, Zisapel N, Srinivasan V, Cardinali DP (2005) Melatonin and sleep in aging population. Exp Gerontol 40:911–925

    Article  PubMed  CAS  Google Scholar 

  9. Campos FL, Silva-Júnior FP, De Bruin VMS, De Bruin PFC (2004) Melatonin Improves Sleep in Asthma. Am J Resp Crit Care 170:947–951

    Article  Google Scholar 

  10. Dabbeni-Sala F, Di Santo S, Franceschini D, Skaper SD, Giusti P (2001) Melatonin protects against 6-OHDA-induced neurotoxicity in rats: a role for mitochondrial complex I activity. FASEB J 15:164–170

    Article  PubMed  CAS  Google Scholar 

  11. Absi E, Ayala A, Machado A, Parrado J (2000) Protective effect of melatonin against the 1-methyl-4-phenylpyridinium-induced inhibition of complex I of the mitochondrial respiratory chain. J Pineal Res 29:40–47

    Article  PubMed  CAS  Google Scholar 

  12. Willis GL, Armstrong SM (1999) A therapeutic role for melatonin antagonism in experimental models of Parkinson's disease. Physiol Behav 66:785–795

    Article  PubMed  CAS  Google Scholar 

  13. Rechtshaffen A, Kales A, editors. A Manual Of Standardized Terminology, Techniques And Scoring System For Sleep Stages Of Human Subjects. Los Angeles CA: BIS/BRI, UCLA; 1968

  14. Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ (1989) The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res 28:193–213

    Article  PubMed  CAS  Google Scholar 

  15. Johns MW (1991) A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 14:540–545

    PubMed  CAS  Google Scholar 

  16. Brzezinski A, Vangel MG, Wurtman RJ, Norrie G, Zhdanova I, Ben-Shushan A, Ford I (2005) Effects of exogenous melatonin on sleep: a meta-analysis. Sleep Med Rev 9:41–50

    Article  PubMed  Google Scholar 

  17. Vgontzas AN, Bixler EO, Kales A, Manfredi RL, Tyson K (1994) Validity and clinical utility of sleep laboratory criteria for insomnia. Int J Neurosci 77:11–21

    Article  PubMed  CAS  Google Scholar 

  18. Dowling GA, Mastick J, Colling E, Carter JH, Singer CM, Aminoff MJ (2005) Melatonin for sleep disturbances in Parkinson's Disease. Sleep Med 6:459–466

    Article  PubMed  Google Scholar 

  19. Arnulf I, Konofal E, Merino-Andreu M, Houeto JL, Mesnage V, Welter ML, Lacomblez L, Golmard JL, Derenne JP, Agid Y (2002) Parkinson's disease and sleepiness: an integral part of PD. Neurology 58:1019–1024

    PubMed  CAS  Google Scholar 

  20. Happe S, Anderer P, Pirker W, Klosch G, Gruber G, Saletu B, Zeitlhofer J (2004) Sleep microstructure and neurodegeneration as measured by [123I]beta-CIT SPECT in treated patients with Parkinson's disease. J Neurol 251:1465–1471

    Article  PubMed  Google Scholar 

  21. Kaynak D, Kiziltan G, Kaynak H, Benbir G, Uysal O (2005) Sleep and sleepiness in patients with Parkinson's disease before and after dopaminergic treatment. Eur J Neurol 12:199–207

    Article  PubMed  CAS  Google Scholar 

  22. Romigi A, Brusa L, Marciani MG, Pierantozzi M, Placidi F, Izzi F, Sperli F, Testa F, Stanzione P (2005) Sleep episodes and daytime somnolence as result of individual susceptibility to different dopaminergic drugs in a PD patient: a polysomnographic study. J Neurol Sci 228:7–10

    Article  PubMed  CAS  Google Scholar 

  23. Diederich NJ, Vaillant M, Leischen M, Mancuso G, Golinval S, Nati R, Schlesser M (2005) Sleep apnea syndrome in Parkinson's disease. A casecontrol study in 49 patients. Mov Disord 20:1413–1418

    Article  PubMed  Google Scholar 

  24. Monte FS, da Silva-Junior FP, Braga- Neto P, Nobre e Souza MA, Sales de Bruin VM (2004) Snoring and excessive daytime sleepiness in Parkinson's disease. J Neurol Sci 217:41–45

    Article  Google Scholar 

  25. Seabra ML, Bignotto M, Pinto LR Jr, Tufik S (2000) Randomized, doubleblind clinical trial, controlled with placebo, of the toxicology chronic melatonin treatment. J Pineal Res 29:193–200

    Article  PubMed  CAS  Google Scholar 

  26. Dowling GA, Mastick J, Aminoff MJ (2003) Melatonin treatment for insomnia in Parkinson's disease: A pilot Study. Sleep Research Online 5:99–103

    Google Scholar 

  27. Bruguerolle B, Simon N (2002) Biologic rhythms and Parkinson's disease: a chronopharmacologic approach to considering fluctuations in function. Clin Neuropharmacol 25:194–201

    Article  PubMed  Google Scholar 

  28. Bordet R, Devos D, Brique S, Touitou Y, Guieu JD, Libersa C, Destee A (2003) Study of circadian melatonin secretion pattern at different stages of Parkinson's disease. Clin Neuropharmacol 26:65–72

    Article  PubMed  CAS  Google Scholar 

  29. Camara Magalhaes S, Vitorino Souza C, Rocha Dias T, Felipe Carvalhedo de Bruin P, Meireles Sales de Bruin V (2005) Lifestyle regularity measured by the social rhythm metric in Parkinson's disease. Chronobiol Int 22:917–924

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Dept. of Medicine, Federal University of Ceará, Rua Prof. Costa Mendes 1608 – 4 Andar, 60430 040, Fortaleza (Ceará), Brazil

    Pedro Felipe Carvalhedo de Bruin, Lívia Ariane Lopes, Maria Cecília Magalhães & Veralice Meireles Sales de Bruin

  2. Dept. of Pharmacy, Federal University of Ceará, Ceará, Brazil

    Camila Andrade Mendes Medeiros

  3. Dept. of Psychobiology Paulo, Federal University of São , São Paulo, Brazil

    Maria de Lourdes Seabra

Authors
  1. Camila Andrade Mendes Medeiros
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  2. Pedro Felipe Carvalhedo de Bruin
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  3. Lívia Ariane Lopes
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  4. Maria Cecília Magalhães
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  5. Maria de Lourdes Seabra
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  6. Veralice Meireles Sales de Bruin
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Correspondence to Veralice Meireles Sales de Bruin.

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Medeiros, C.A.M., Carvalhedo de Bruin, P.F., Lopes, L.A. et al. Effect of exogenous melatonin on sleep and motor dysfunction in Parkinson's disease. J Neurol 254, 459–464 (2007). https://doi.org/10.1007/s00415-006-0390-x

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  • DOI: https://doi.org/10.1007/s00415-006-0390-x

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