Abstract
Background
Patients with dementia may suffer from poor sleep quality as well as insomnia and sleep–wake cycle alterations.
Objectives
The main objective of this study was to evaluate the efficacy of melatonin in improving sleep quality.
Methods
This was a single-center randomized, double-blinded, placebo-controlled study carried out on outpatients with dementia and sleep alterations (according to Diagnostic and Statistical Manual V criteria) from January 2016 to December 2016. Patients aged 65 years or over with a diagnosis of mild–moderate dementia (Clinical Dementia Rating 1–2) were included. Patients were randomized to receive either 5 mg of melatonin or placebo every night for 8 weeks. The primary outcome was sleep quality according to the Pittsburgh Sleep Quality Index (PSQI). Secondary measurements included Mini-Mental State Examination, Neuropsychiatric Inventory (NPI), Geriatric Depression Scale and Katz and Lawton scales for functionality.
Results
40 patients were included (21 in the melatonin group and 19 in the placebo group). Nine patients withdrew from the study, and data of 31 patients were analyzed (16 from the melatonin group and 15 in the placebo group). Baseline characteristics of the population were comparable. PSQI scores improved in both groups at every timepoint compared to baseline, but there were no significant differences between groups. At 8 weeks, there was no difference between groups in any of the secondary outcomes except for the sleep sub-item of the NPI, where melatonin group had lower median scores compared to placebo (1, Interquartile Range = 3, vs. 4.4, Interquartile Range = 4.6, p = 0.03).
Conclusion
Melatonin administered nightly to older persons with dementia was not effective in improving sleep quality. Clinicaltrials.gov Identifier: NCT03066518.
Similar content being viewed by others
References
Frohnhofen H, Schlitzer J, Netzer N (2017) Sleep in older adults and in subjects with dementia. Z Gerontol Geriatr 50:603–608
Cipriani G, Lucetti C, Danti S, Nuti A (2015) Sleep disturbances and dementia. Psychogeriatrics 15:65–74
Beaulieu-Bonneau S, Hudon C (2009) Sleep disturbances in older adults with mild cognitive impairment. Int Psychogeriatr 21:654–666
Woods DL, Phillips LR, Martin JL (2011) Biological basis for sleep disturbance and behavioral symptoms in dementia: a biobehavioral model. Res Gerontol Nurs 4:281–293
Malhotra RK (2018) Neurodegenerative disorders and sleep. Sleep Med Clin 13:63–70
Kinnunen KM, Vikhanova A, Livingston G (2017) The management of sleep disorders in dementia: an update. Curr Opin Psychiatry 30:491–497
Ooms S, Ju YE (2016) Treatment of sleep disorders in dementia. Curr Treat Options Neurol 18:40
Tordjman S, Chokron S, Delorme R, Charrier A, Bellissant E, Jaafari N et al (2017) Melatonin: pharmacology, functions and therapeutic benefits. Curr Neuropharmacol 15:434–443
Xu J, Wang LL, Dammer EB, Li CB, Xu G, Chen SD et al (2015) Melatonin for sleep disorders and cognition in dementia: a meta-analysis of randomized controlled trials. Am J Alzheimers Dis Other Demen 30:439–447
McCleery J, Cohen DA, Sharpley AL (2016) Pharmacotherapies for sleep disturbances in dementia. Cochrane Database Syst Rev 11:9178
Hughs CP, Berg L, Danziger WL, Coben LA, Martin RL (1982) A new clinical scale for the staging of dementia. Am J Psychiatry 140:566–572
Buysse DJ, Reynolds CF, 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
Folstein MF, Folstein SE, McHugh PR (1975) «Mini-Mental State » . A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198
Lawton MP, Brody EM (1969) Assessment of older people: self- maintaining and instrumental activities of daily living. Gerontologist 9:179–186
Katz S, Ford AB, Moskowitz RW, Jackson BA, Jaffe MW (1963) Studies of illness in the aged. The index of ADL: a standarized measure of biological and psychosocial function. JAMA 185:914–919
Kaiser MJ, Bauer JM, Ramsch C, Uter W, Guigoz Y, Cederholm T et al (2009) Validation of the Mini Nutritional Assessment short-form (MNAA (R)-SF): a practical tool for identification of nutritional status. J Nutr Health Aging 13:782–788
Shelk JI, Yesavage JA (1986) Geriatric Depression Scale (GDS): recent evidence and development of a shorter version. In: Brink TL (ed) Clinical Gerontology: a guide to assessment and intervention. Haworth Press, New York
Zarit SH, Reever KE, Bach-Peterson J (1980) Relatives of the impaired elderly: correlates of feelings of burden. Gerontologist 20:649–655
Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J (1994) The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology 44:2308–2314
Chien MY, Chen HC (2015) Poor sleep quality is independently associated with physical disability in older adults. J Clin Sleep Med 11:225–232
Sterniczuk R, Theou O, Rusak B, Rockwood K (2013) Sleep disturbance is associated with incident dementia and mortality. Curr Alzheimer Res 10:767–775
Pandi-Perumal SR, Zisapel N, Srinivasan V, Cardinali DP (2005) Melatonin and sleep in aging population. Exp Gerontol 40:911–925
Cherniack EP (2006) The use of alternative medicine for the treatment of insomnia in the elderly. Psychogeriatrics 6:21–30
OldeRikkert MG, Rigaud AS (2001) Melatonin in elderly patients with insomnia. A systematic review. Z Gerontol Geriatr 34:491–497
Singer C, Tractenberg RE, Kaye J, Schafer K, Gamst A, Grundman M et al (2003) Alzheimer’s Disease Cooperative Study. A multicenter, placebo-controlled trial of melatonin for sleep disturbance in Alzheimer’s disease. Sleep 26:893–901
Cardinali DP, Brusco LI, Liberczuk C, Furio AM (2002) The use of melatonin in Alzheimer’s disease. Neuro Endocrinol Lett 23:20–23
de Jonghe A, Korevaar JC, van Munster BC, de Rooij SE (2010) Effectiveness of melatonin treatment on circadian rhythm disturbances in dementia. Are there implications for delirium? A systematic review. Int J Geriatr Psychiatry 25:1201–1208
Wade AG, Farmer M, Harari G, Fund N, Laudon M, Nir T et al (2014) Add-on prolonged-release melatonin for cognitive function and sleep in mild to moderate Alzheimer’s disease: a 6-month, randomized, placebo-controlled, multicenter trial. ClinInterv Aging 9:947–961
Furio AM, Brusco LI, Cardinali DP (2007) Possible therapeutic value of melatonin in mild cognitive impairment: a retrospective study. J Pineal Res 43:404–409
Cardinali DP, Vigo DE, Olivar N, Vidal MF, Furio AM, Brusco LI (2012) Therapeutic application of melatonin in mild cognitive impairment. Am J Neurodegener Dis 1:280–291
Cardinali DP, Furio AM, Brusco LI (2011) The use of chronobiotics in the resynchronization of the sleep/wake cycle. Therapeutical application in the early phases of Alzheimer’s disease. Recent Pat EndocrMetab Immune Drug Discov 5:80–90
van der Lek Riemersma RF, Swaab DF, Twisk J, Hol EM, Hoogendijk WJ, Van Someren EJ (2008) Effect of bright light and melatonin on cognitive and noncognitive function in elderly residents of group care facilities: a randomized controlled trial. JAMA. 299:2642–2655
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare no conflict of interest.
Ethical approval
The study protocol, informed consents, and amendments were approved in writing by the appropriate local site Independent Ethics Committee (IEC)/Institutional Review Boards (IRB) (Ethics Committee of the UANL School of Medicine) and all procedures were carried out in accordance with the standards laid out in the Declaration of Helsinki.
Informed consent
Informed consent was obtained from all individual participants included in the study.
Rights and permissions
About this article
Cite this article
Morales-Delgado, R., Cámara-Lemarroy, C.R., Salinas-Martínez, R. et al. A randomized placebo-controlled trial evaluating the effect of melatonin on sleep quality in patients with mild–moderate dementia. Eur Geriatr Med 9, 449–454 (2018). https://doi.org/10.1007/s41999-018-0068-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s41999-018-0068-9