FPIN's Clinical Inquiries

Melatonin to Treat Insomnia in Older Adults


Am Fam Physician. 2021 Sep ;104(2):297-298.

Clinical Question

How safe and effective are melatonin receptor agonists for treating insomnia in older adults?

Evidence-Based Answer

Melatonin preparations reduce sleep-onset latency, increase total sleep time, and slightly improve sleep efficiency. (Strength of Recommendation [SOR]: B, based on meta-analysis of primarily small randomized crossover trials.) Prolonged-release melatonin reduces sleep-onset latency in older adults and has rates of adverse effects similar to those of placebo. (SOR: B, based on randomized controlled trials [RCTs] from a single research team.) Ramelteon (Rozerem; a melatonin receptor agonist) also reduces sleep-onset latency and may increase total sleep time. (SOR: B, based on large RCTs from a single research team.) Ramelteon use is not associated with severe traumatic accidents (e.g., falls, head injuries, motor vehicle crashes). (SOR: B, based on a retrospective cohort study.)

Evidence Summary


A systematic review and meta-analysis included 15 primarily randomized crossover trials (N = 284) using objective measures to assess the effect of melatonin on sleep.1 Healthy young adults (six trials; n = 71) and adults older than 50 years (seven trials; n = 195) with insomnia comprised most of the participants. Eleven trials used oral immediate-release melatonin (0.1 to 80 mg nightly, with most patients receiving 1 to 5 mg nightly), and four used prolonged-release melatonin (0.5 to 2.5 mg nightly). Overall, melatonin treatment reduced sleep-onset latency (mean difference [MD] = −7.5 minutes; 95% CI, −9.9 to −5.2), increased total sleep time (MD = 12.8 minutes; 95% CI, 2.9 to 22.8), and improved sleep efficiency (MD = 2%; 95% CI, 0.2% to 4.2%) compared with placebo. Authors performed no subanalyses of older adults or various types of melatonin and did not address possible adverse effects. Most studies were crossover trials, enrolled fewer than 30 patients, and gave medication for two weeks or less.

Three industry-sponsored RCTs evaluated prolonged-release melatonin in older adults.24 In the first study, researchers randomized 281 patients 65 to 80 years of age (mean age = 71 years) with primary insomnia to prolonged-release

Address correspondence to Jon O. Neher, MD, at jon_neher@valleymed.org. Reprints are not available from the authors.

Author disclosure: No relevant financial affiliations.

Copyright © Family Physicians Inquiries Network. Used with permission.


show all references

1. Brzezinski A, Vangel MG, Wurtman RJ, et al. Effects of exogenous melatonin on sleep: a meta-analysis. Sleep Med Rev. 2005;9(1):41–50....

2. 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.

3. 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):2597–2605.

4. 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):372–380.

5. Roth T, Seiden D, Sainati S, et al. Effects of ramelteon on patient-reported sleep latency in older adults with chronic insomnia. Sleep Med. 2006;7(4):312–318.

6. Mini LJ, Wang-Weigand S, Zhang J. Self-reported efficacy and tolerability of ramelteon 8 mg in older adults experiencing severe sleep-onset difficulty. Am J Geriatr Pharmacother. 2007;5(3):177–184.

7. Roth T, Seiden D, Wang-Weigand S, et al. A 2-night, 3-period, crossover study of ramelteon's efficacy and safety in older adults with chronic insomnia. Curr Med Res Opin. 2007;23(5):1005–1014.

8. Avidan AY, Palmer LA, Doan JF, et al. Insomnia medication use and the probability of an accidental event in an older adult population. Drug Healthc Patient Saf. 2010;2:225–232.

9. Choosing Wisely. American Academy of Sleep Medicine. Five things physicians and patients should question. December 2, 2014. Accessed July 16, 2020. https://www.choosingwisely.org/wp-content/uploads/2015/02/AASM-Choosing-Wisely-List.pdf

10. Sateia MJ, Buysse DJ, Krystal AD, et al. Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2017;13(2):307–349.

Clinical Inquiries provides answers to questions submitted by practicing family physicians to the Family Physicians Inquiries Network (FPIN). Members of the network select questions based on their relevance to family medicine. Answers are drawn from an approved set of evidence-based resources and undergo peer review. The strength of recommendations and the level of evidence for individual studies are rated using criteria developed by the Evidence-Based Medicine Working Group (https://www.cebm.net).

The complete database of evidence-based questions and answers is copyrighted by FPIN. If interested in submitting questions or writing answers for this series, go to https://www.fpin.org or email: questions@fpin.org.

This series is coordinated by John E. Delzell Jr., MD, MSPH, associate medical editor.

A collection of FPIN's Clinical Inquiries published in AFP is available at https://www.aafp.org/afp/fpin.



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