Advertisement

Drugs & Aging

, Volume 29, Issue 11, pp 911–923 | Cite as

Melatonin Prolonged Release

In the Treatment of Insomnia in Patients Aged ≥55 years
  • Katherine A. Lyseng-Williamson
Adis Drug Profile

Abstract

Melatonin prolonged release (PR) 2 mg is approved for the treatment of primary insomnia characterized by poor sleep quality in patients aged ≥55 years in the EU and elsewhere. Patients may receive treatment with melatonin PR for up to 13 weeks. Production of endogenous nocturnal melatonin, which helps regulate circadian rhythm, may be decreased in older adults. Administration of melatonin PR 2 mg 1–2 h before bedtime mimics the natural secretion pattern of melatonin, thereby leading to improvements in the circadian regulation of the sleep–wake cycle. In older adults, melatonin PR 2 mg had no effect on psychomotor functions, memory recall or driving skills during the night or the next morning relative to placebo, and was associated with significantly less impairment on many of these tasks relative to zolpidem 10 mg alone or in combination with melatonin PR 2 mg. In 3-week and 6-month, randomized, double-blind clinical trials in patients with primary insomnia aged ≥55 years, melatonin PR 2 mg 1–2 h before bedtime was associated with significant improvements relative to placebo in many sleep and daytime parameters, including sleep quality and latency, morning alertness and health-related quality of life. Melatonin PR 2 mg was very well tolerated in clinical trials in older patients, with a tolerability profile that was similar to that of placebo. Short- or longer-term treatment with melatonin PR 2 mg was not associated with dependence, tolerance, rebound insomnia or withdrawal symptoms.

Keywords

Melatonin Zolpidem Pittsburgh Sleep Quality Index Sleep Latency Zopiclone 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Disclosure

The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made by the authors on the basis of scientific and editorial merit.

References

  1. 1.
    Wilson SJ, Nutt DJ, Alford C, et al. British Association for Psychopharmacology consensus statement on evidence-based treatment of insomnia, parasomnias and circadian rhythm disorders. J Psychopharmacol. 2010;24(11):1577–601.PubMedCrossRefGoogle Scholar
  2. 2.
    Bloom HG, Ahmed I, Alessi CA, et al. Evidence-based recommendations for the assessment and management of sleep disorders in older persons. J Am Geriatr Soc. 2009;57(5):761–89.PubMedCrossRefGoogle Scholar
  3. 3.
    Schutte-Rodin S, Broch L, Buysse D, et al. Clinical guideline for the evaluation and management of chronic insomnia in adults. J Clin Sleep Med. 2008;4(5):487–504.PubMedGoogle Scholar
  4. 4.
    Zisapel N. Drugs for insomnia. Expert Opin Emerg Drugs. 2012;17(3):299–317.PubMedCrossRefGoogle Scholar
  5. 5.
    Léger D, Morin CM, Uchiyama M, et al. Chronic insomnia, quality-of-life, and utility scores: comparison with good sleepers in a cross-sectional international survey. Sleep Med. 2012;13(1):43–51.PubMedCrossRefGoogle Scholar
  6. 6.
    Roth T, Franklin M, Bramley TJ. The state of insomnia and emerging trends. Am J Managed Care. 2007;13(5 Suppl):S117–20.Google Scholar
  7. 7.
    Ohayon MM, Carskadon MA, Guilleminault C, et al. Meta-analysis of quantitative sleep parameters from childhood to old age in healthy individuals: developing normative sleep values across the human lifespan. Sleep. 2004;27(7):238–9.Google Scholar
  8. 8.
    Conn DK, Madan R. Use of sleep-promoting medications in nursing home residents: risks versus benefits. Drugs Aging. 2006;23(4):271–87.PubMedCrossRefGoogle Scholar
  9. 9.
    Glass J, Lanctot KL, Herrmann N, et al. Sedative hypnotics in older people with insomnia: meta-analysis of risks and benefits. BMJ. 2005;331(7526):1169.PubMedCrossRefGoogle Scholar
  10. 10.
    Huang AR, Mallet L, Rochefort CM, et al. Medication-related falls in the elderly: causative factors and preventative strategies. Drugs Aging. 2012;29(5):359–76.PubMedCrossRefGoogle Scholar
  11. 11.
    McIntyre IM, Norman TR, Burrows GD, et al. Alterations to plasma melatonin and cortisol after evening alprazolam administration in humans. Chronobiol Int. 1993;10(3):205–13.PubMedCrossRefGoogle Scholar
  12. 12.
    Terzano MG, Rossi M, Palomba V, et al. New drugs for insomnia: comparative tolerability of zopiclone, zolpidem and zaleplon. Drug Saf. 2003;26(4):61–82.CrossRefGoogle Scholar
  13. 13.
    Zammit G. Comparative tolerability of newer agents for insomnia. Drug Saf. 2009;32(9):735–48.PubMedCrossRefGoogle Scholar
  14. 14.
    Dolder C, Nelson M, McKinsey J. Use of non-benzodiazepine hypnotics in the elderly: are all agents the same? CNS Drugs. 2007;21(5):389–405.PubMedCrossRefGoogle Scholar
  15. 15.
    Srinivasan V, Pandi-Perumal SR, Trahkt I, et al. Melatonin and melatonergic drugs on sleep: possible mechanisms of action. Int J Neurosci. 2009;119(6):821–46.PubMedCrossRefGoogle Scholar
  16. 16.
    Cardinali DP, Srinivasan V, Brzezinski A, et al. Melatonin and its analogs in insomnia and depression. J Pineal Res. 2012;52(4):365–75.PubMedCrossRefGoogle Scholar
  17. 17.
    Circadin 2 mg prolonged-release tablets: summary of product characteristics. London: European Medicines Agency; 2012.Google Scholar
  18. 18.
    Hardeland R, Poeggeler B, Srinivasan V, et al. Melatonergic drugs in clinical practice. Arzneimittelforschung. 2008;58(1):1–10.PubMedGoogle Scholar
  19. 19.
    Pandi-Perumal SR, Srinivasan V, Spence DW, et al. Role of the melatonin system in the control of sleep: therapeutic implications. CNS Drugs. 2007;21(12):995–1018.PubMedCrossRefGoogle Scholar
  20. 20.
    Hardeland R. New approaches in the management of insomnia: weighing the advantages of prolonged-release melatonin and synthetic melatoninergic agonists. Neuropsychiatr Dis Treat. 2009;5(1):341–54.PubMedCrossRefGoogle Scholar
  21. 21.
    Haimov I. Melatonin rhythm abnormalities and sleep disorders in the elderly. CNS Spectr. 2001;6(6):502–6.PubMedGoogle Scholar
  22. 22.
    Leger D, Laudon M, Zisapel N. Nocturnal 6-sulfatoxymelatonin excretion in insomnia and its relation to the response to melatonin replacement therapy. Am J Med. 2004;116(2):91–5.PubMedCrossRefGoogle Scholar
  23. 23.
    Garfinkel D, Laudon M, Nof D, et al. Improvement of sleep quality in elderly people by controlled-release melatonin. Lancet. 1995;346(8974):541–4.PubMedCrossRefGoogle Scholar
  24. 24.
    Garfinkel D, Laudon M, Zisapel N. Improvement of sleep quality by controlled-release melatonin in benzodiazepine-treated elderly insomniacs. Arch Gerontol Geriatr. 1997;24(2):223–31.PubMedCrossRefGoogle Scholar
  25. 25.
    Lissoni P, Rovelli F, Pittalis S, et al. Therapy with melatonin does not suppress its endogenous production in healthy volunteers [in Italian]. Recenti Prog Med. 1999;90(2):84–5.PubMedGoogle Scholar
  26. 26.
    Lemoine P, Garfinkel D, Laudon M, et al. Prolonged-release melatonin for insomnia: an open-label long-term study of efficacy, safety, and withdrawal. Ther Clin Risk Manag. 2011;7:301–11.PubMedGoogle Scholar
  27. 27.
    Garfinkel D, Zorin M, Wainstein J, et al. Efficacy and safety of prolonged-release melatonin in insomnia patients with diabetes: a randomized, double-blind, crossover study. Diabetes Metab Syndr Obes. 2011;4:307–13.PubMedGoogle Scholar
  28. 28.
    Luthringer R, Muzet M, Zisapel N, et al. The effect of prolonged-release melatonin on sleep measures and psychomotor performance in elderly patients with insomnia. Int Clin Psychopharmacol. 2009;24(5):239–49.PubMedCrossRefGoogle Scholar
  29. 29.
    Otmani S, Demazieres A, Staner C, et al. Effects of prolonged-release melatonin, zolpidem, and their combination on psychomotor functions, memory recall, and driving skills in healthy middle aged and elderly volunteers. Hum Psychopharmacol Clin Exp. 2008;23(8):693–705.CrossRefGoogle Scholar
  30. 30.
    Otmani S, Metzger D, Guichard N, et al. Effects of prolonged-release melatonin and zolpidem on postural stability in older adults. Hum Psychopharmacol Clin Exp. 2012;27(3):270–6.CrossRefGoogle Scholar
  31. 31.
    Paul MA, Gray G, Kenny G, et al. Impact of melatonin, zaleplon, zopiclone, and temazepam on psychomotor performance. Aviat Space Environ Med. 2003;74(12):1263–70.PubMedGoogle Scholar
  32. 32.
    European public assessment report for Circadin: scientific discussion. London: European Medicines Agency; 2007.Google Scholar
  33. 33.
    Aperis G, Prakash P, Paliouras C, et al. The role of melatonin in patients with chronic kidney disease undergoing haemodialysis. J Ren Care. 2012;38(2):86–92.PubMedCrossRefGoogle Scholar
  34. 34.
    Lemoine P, Nir T, Laudon M, et al. Prolonged-release melatonin improves sleep quality and morning alertness in insomnia patients aged 55 years and older and has no withdrawal effects. J Sleep Res. 2007;16(4):372–80.PubMedCrossRefGoogle Scholar
  35. 35.
    Wade AG, Ford I, Crawford G, et al. Efficacy of prolonged release melatonin in insomnia patients aged 55–80 years: quality of sleep and next-day alertness outcomes. Curr Med Res Opin. 2007;23(10):2597–605.PubMedCrossRefGoogle Scholar
  36. 36.
    Wade AG, Crawford G, Ford I, et al. Prolonged release melatonin in the treatment of primary insomnia: evaluation of the age cut-off for short- and long-term response. Curr Med Res Opin. 2011;27(1):87–98.PubMedCrossRefGoogle Scholar
  37. 37.
    Parrott AC, Hindmarch I. The Leeds Sleep Evaluation Questionnaire in psychopharmacological investigations: a review. Psychopharmacology (Berl). 1980;71(2):173–9.CrossRefGoogle Scholar
  38. 38.
    Backhaus J, Junghanns K, Broocks A, et al. Test–retest reliability and validity of the Pittsburgh Sleep Quality Index in primary insomnia. J Psychosom Res. 2002;53(3):737–40.PubMedCrossRefGoogle Scholar
  39. 39.
    Bech P, Olsen LR, Kjoller M, et al. Measuring well-being rather than the absence of distress symptoms: a comparison of the SF-36 Mental Health subscale and the WHO-Five Well-Being Scale. Int J Methods Psychiatr Res. 2003;12(2):85–91.PubMedCrossRefGoogle Scholar
  40. 40.
    Wade AG, Ford I, Crawford G, et al. Nightly treatment of primary insomnia with prolonged release melatonin for 6 months: a randomized placebo controlled trial on age and endogenous melatonin as predictors of efficacy and safety. BMC Med. 2010;8:51.PubMedCrossRefGoogle Scholar
  41. 41.
    Lemoine P, Wade AG, Katz A, et al. Efficacy and safety of prolonged-release melatonin for insomnia in middle-aged and elderly patients with hypertension: a combined analysis of controlled clinical trials. Integr Blood Press Control. 2012;5:9–17.PubMedGoogle Scholar
  42. 42.
    Garfinkel D, Zisapel N, Wainstein J, et al. Facilitation of benzodiazepine discontinuation by melatonin: a new clinical approach. Arch Intern Med. 1999;159(20):2456–60.PubMedCrossRefGoogle Scholar
  43. 43.
    Kunz D, Bineau S, Maman K, et al. Benzodiazepine discontinuation with prolonged-release melatonin: hints from a German longitudinal prescription database. Expert Opin Pharmacother. 2012;13(1):9–16.PubMedCrossRefGoogle Scholar
  44. 44.
    British Medical Association and the Royal Pharmaceutical Society of Great Britain. British national formulary. No. 63. London: BMJ Publishing Group Ltd and RPS Publishing; 2012.Google Scholar

Copyright information

© Springer International Publishing Switzerland 2012

Authors and Affiliations

  1. 1.AdisAucklandNew Zealand

Personalised recommendations