Melatonin for the management of sleep disturbances in older adults

Contributed by:

Shailee Siddhpuria, MD¹ - View Dr. Siddhpuria's bio
Shabbir M.H. Alibhai, MD, MSc, FRCPC^2,3
Christina Reppas-Rindlisbacher, MD, FRCPC^2,3

¹Department of Family and Community Medicine, University of Toronto, Toronto, Canada  
²Division of General Internal Medicine and Geriatrics, Sinai Health System and the University Health Network, Toronto, Canada 
³Department of Medicine, University of Toronto, Toronto, Canada

Case:

Mrs. J, a 78-year-old woman, presents with difficulty sleeping. She lives independently and has a history of hypertension, osteoarthritis, osteoporosis and mild cognitive impairment. She is currently taking amlodipine, acetaminophen, alendronate and vitamin D. Mrs. J reports waking up multiple times during the night and feeling fatigued during the day, which worsens her joint pain and cognitive symptoms. She has tried over-the-counter sleep aids like diphenhydramine but discontinued them due to daytime drowsiness and confusion. She is concerned about the potential side effects of sleep medications, particularly their impact on her memory and risk of falls.

Issue:

Is melatonin a safe and effective treatment for managing sleep disturbances in older adults?

Background:

Sleep disturbances, particularly insomnia, are common in older adults, affecting about 50% of community-dwelling seniors.¹ These can be primary (e.g., insomnia, sleep apnea) or secondary to medical conditions, psychiatric issues or medications. Older adults are more susceptible to sleep problems, including increased time to sleep onset and decreased overall sleep time and efficiency.² Sleep impairment can subsequently lead to daytime fatigue, falls and reduced quality of life.³

Sedative-hypnotics such as benzodiazepines (BZDs) and Z-drugs are frequently prescribed but carry significant risks, including cognitive impairment, falls and dependence.^4,5 Melatonin, an endogenous hormone that regulates the sleep-wake cycle, is commonly perceived to be a safer alternative and is widely available in synthetic preparations over-the counter.

Evidence:

Several studies have evaluated melatonin’s efficacy in improving sleep in older adults. A 2013 meta-analysis of 19 randomized controlled trials showed small but statistically significant improvements, including reduced sleep onset latency by an average of seven minutes (95% CI: 4.37 to 9.75, p < 0.001) and increased total sleep time by eight minutes (95% CI: -4.02 to 20.98, p = 0.184) compared to placebo.⁶ More recently, a 2022 systematic review found significantly improved sleep outcomes, with subjects falling asleep an average of 13.8 minutes earlier and experiencing 21 minutes longer total sleep time compared to placebo. Objective measures showed a moderate effect on sleep latency (SMD = 0.74, p < 0.001) and on total sleep time (SMD = 0.16, p = 0.04). However, this review did not distinguish between the effects of melatonin and ramelteon (a melatonin receptor agonist not available in Canada) individually, as both were grouped together in analyses.⁷ In studies focused specifically on adults over 55 years of age there were modest improvements in sleep latency and subjective measures of sleep quality with doses of prolonged-release melatonin between 0.3 and 1 mg.^8-9

Overall, the evidence is limited by small sample sizes, variable dosing and heterogeneous formulations. For this reason, the most recent guidelines from the American Academy of Sleep Medicine provide only a weak recommendation for melatonin in delayed sleep-wake phase disorder and recommend against its use for chronic insomnia.¹⁰

The major advantage of melatonin is its safety. Unlike BZDs and Z-drugs, melatonin does not increase the risk of falls or cognitive impairment, making it a safer option for older adults.¹² Common side effects include headaches, dizziness, nausea and daytime drowsiness, but these occur at similar rates in placebo groups.^11,12 Melatonin does not cause drug dependence or tolerance and unlike BZDs and Z-drugs, there is no evidence that cessation of therapy causes increased sleep disturbance or “rebound insomnia.”¹¹ Even its use in frail older adults with dementia appears safe based on data from four studies.¹³ For this reason, the British Pharmacology Association recommends that prolonged release melatonin should be tried first when a hypnotic is indicated in patients over 55 years.¹⁴

Like many medications, melatonin is metabolized by cytochrome-P450 enzymes in the liver and eventually excreted in the kidneys. Although very few drug interactions have been studied, the available evidence suggests increased serum concentrations may occur in patients taking SSRIs.^15,16 There may also be a risk of compound effects in patients taking other sedatives concomitantly. For example, a study of older adults found that melatonin increased zolpidem’s effect on impaired psychomotor function and driving skills.¹⁷ As with all pharmacotherapies in older adults, clinicians should start with low initial doses and monitor closely for adverse effects.

Clinicians should also note that the quality and content of melatonin dietary supplements varies, with some products containing higher or lower doses than advertised.¹⁸ Lower doses (0.3 to 3 mg) taken 30 minutes to one hour before bedtime may be safer in older adults, as higher doses can cause prolonged elevated melatonin levels and daytime drowsiness.¹⁹ Prolonged release formulations have better evidence in older adults, although they can be more difficult to find in lower doses. Given the uncertainty of plasma concentrations due to variable dosing and absorption, it is important that clinicians view melatonin as a medication rather than a harmless dietary supplement, and follow the mantra of “start low, go slow” while counseling patients accordingly.

Summary:

Melatonin represents a reasonable first-line option for managing sleep disturbances in older adults, particularly those with frailty or multimorbidity, after non-pharmacological interventions such as sleep hygiene and cognitive behavioral therapy have been considered.²⁰ Given its low risk of adverse effects, melatonin is a safer alternative to sedative-hypnotics like BZDs and Z-drugs, which are associated with a high risk of falls and cognitive impairment in older adults.²¹

While the evidence supporting melatonin’s efficacy is mixed, its safety profile makes it an appropriate option for a three- to four-week trial at a dose of 1-3 mg, ideally in a prolonged release formulation, taken 30 minutes to one hour before bedtime. Clinicians should use their judgment in balancing the modest benefits with the minimal risks.

Case outcome:

For Mrs. J, melatonin offers a low-risk option to address her sleep disturbances, especially given her concerns about cognitive side effects and falls. After reinforcing non-pharmacological strategies, you prescribe a short trial of low-dose prolonged-release melatonin (1–3 mg) taken before bedtime to help improve sleep onset and quality without compromising safety. Given her mild cognitive impairment and history of daytime drowsiness with other agents, close monitoring is essential. If the melatonin proves ineffective, further evaluation or referral may be warranted to explore other underlying causes or treatment options.

References:

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