Tuft C, Matar E, Menczel Schrire Z, Grunstein RR, Yee BJ, Hoyos CM. Current Insights into the Risks of Using Melatonin as a Treatment for Sleep Disorders in Older Adults. Clin Interv Aging. 2023;18:49-59. Published 2023 Jan 12. doi:10.2147/CIA.S361519
This narrative review summarizes literature findings regarding the safety of using melatonin in the gaining population (>65 years old) for sleep disorders. There is limited data specific to this age population, as many studies will include age groups to include younger adults. With the current data available, the authors of this review article concluded that melatonin, when administered at the lowest effective dose, is a safe treatment option for sleep disorders in older adults.
Our clinical takeaways from the article
With increased use and variations in doses of melatonin, we are committed to monitoring the safeness of its use. As it is well-documented that endogenous production of melatonin decreases with age, and therefore, older adults can experience sleep disorders. In fact, as stated in the article, 50% of individuals 60 years and older report insomnia, circadian rhythm sleep-wake phase disorders are more common, and sleep disturbances are present in diseases of aging, including Alzheimer’s disease, dementia, and Parkinson’s disease.
This narrative review summarized current evidence and reported that melatonin is a safe therapy for sleep disorders in older adults, with non-statistical significance in reported adverse effects, of which the most common are headaches, daytime fatigue, and dizziness. It is best used at the lowest therapeutic dose (<1 mg), administered 30-60 minutes before bed. Since older adults are more likely to have other health conditions and take one or more prescription medications, it is prudent for clinicians to check for possible drug interactions and monitor patients after starting melatonin therapy. Aspects of monitoring include but are not limited to, blood pressure, daytime fatigue, labs (i.e., prothrombin time for those on warfarin), and sleep quality.
This manuscript aimed to review the evidence on the safety profile of melatonin for sleep disorders, when used in older adults, which was classified as those over 65 years of age. The literature search included articles published in the past 40 years that reported on adverse effects, safety, insomnia, and circadian rhythm disorders.
The most common adverse effects included daytime sleepiness, headaches, and dizziness, though most studies found that this was not statistically different that placebo and were “minor clinical significance given the mild nature of the reported symptoms.” Rates of adverse events ranged from 0.008% to 2% of the populations studied, with an increased risk of these events occurring when melatonin is dosed 10 mg or higher. Of note, the studies included a range in the dose of melatonin used and the age groups included were not specific to just those 65 years and older, as seen in Table 1 published in the article.
Image credit: Tuft C, Matar E, Menczel Schrire Z, Grunstein RR, Yee BJ, Hoyos CM. Current Insights into the Risks of Using Melatonin as a Treatment for Sleep Disorders in Older Adults. Clin Interv Aging. 2023;18:49-59. Published 2023 Jan 12. doi:10.2147/CIA.S361519. http://creativecommons.org/licenses/by-nc/3.0/
Besage et al., mean population age in 5th decade of life.
Foley et al., majority were < 65 yo; melatonin dose included 1600 mg, though most common was 2-10 mg, with no increased risk noted with any dose. The article reporting 1600 mg of melatonin was published in 1976 using varying doses of melatonin for 6 severely depressed patients and 2 patients with Huntington’s chorea.
McCleary, et al., Cochrane review, participants had dementia.
In addition to the key findings in Table 1, the authors reported on studies that included older adults without diagnosed sleep disorders, but rather the use of melatonin was for Alzheimer’s disease, Parkinson’s disease, and dementia. Each of the trials reported either no adverse events or a non-statistically significant difference in adverse events (headache, daytime fatigue, dizziness) compared to the placebo.
Additional key findings from the review include:
Peak concentrations of melatonin have been reported as “substantially higher in older adults,” meaning the same dose given to an older adult may be more impactful.
Since older adults are more likely to be on medications, a careful assessment for drug interactions should be completed. The most common interactions include selective serotonin reuptake inhibitors (SSRIs), calcium channel blockers, warfarin, and sedatives. Rather than avoiding melatonin supplementation, it is recommended by the authors that healthcare professionals check for interactions, use a low dose of melatonin, and routinely monitor the patient, including labs, when necessary.
Melatonin has been shown to provide cardiovascular protection, including its ability to decrease blood pressure (6.1 mmHg), therefore, healthcare providers should monitor blood pressure in older adults to avoid hypotension. (Dose and duration of melatonin use for blood pressure were not noted in this study.)
Mild improvements in HbA1C (0.66% 1.15%) have been observed after 5 months of using 2 mg of melatonin.
In perimenopausal women with osteopenia, a modest improvement in bone mineral density was observed after 12 months of using melatonin at a dose of 3 mg per day.
A modest fall in body temperature (0.05 degrees) has been observed in older adults. This thermoregulation effect of melatonin is well established. (Dose and duration of melatonin use were not reported.)
While a majority of the literature includes various age groups, rather than just those over 65 years of age, the authors concluded that melatonin “appears to be safe”, with a low risk (non-statistically significant) of adverse events. Due to the possibility of other medical conditions and medication use in older adults, it is recommended that the lowest, effective dose is utilized for this population, taken 30-60 minutes before bed and that clinicians monitor their patients after beginning therapy. Additionally, further research, specific to this age population, would be warranted.
Limitations noted by Author(s)
There is limited evidence of the long-term safety data in older adults, with many studies including younger adults, teens and children.
Some trials are small.
Several trials have not reported safety data.
Regulation of melatonin as a dietary supplement vs. a pharmaceutical agent differs in countries. The authors noted that when used as a dietary supplement, there is a risk for inappropriate use, lack of medical supervision for adverse events, risk of inaccurate dosing and formulation, including possible contaminants, and varying doses are available. In certain countries, pharmaceutical melatonin requires a prescription, generally for a dose over 1 mg.
“A serious adverse effect from melatonin occurring at a rate of 0.1% would not be detected in trials involving less than 10,000 participants but would affect tens of thousands of patients in the US.”
Article review completed by Kim Ross, DCN
Content reviewed by Deanna Minich, PhD
January 26, 2023