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This article was written by Anna Furman, PharmD. Her full bio is provided below.
Most prescription sleep aids, such as benzodiazepines (BZD), BZD-receptor agonists, and tricyclic antidepressants, should be avoided in older adults per the 2019 American Geriatrics Society Beers criteria.1 These medications put older adults at risk for adverse events such as over-sedation, falls, and fractures.1 Thus, clinicians are left with few sleep medications to choose from including the over-the-counter medication melatonin. While there is a widespread belief that melatonin is a “natural” benign substance, there is limited evidence regarding its safety and efficacy for insomnia.2,3 With aging, endogenous secretion of melatonin by the pineal gland decreases, as do the plasma concentrations of the hormone. In addition to this age-related decline, approximately one-third of people over the age of 50 experience symptoms of insomnia and 50% to 80% of adults over 65 report problems with sleep, which makes people believe in the possible therapeutic role of exogenous melatonin.4,5
The FDA classifies melatonin as a dietary supplement that does not require FDA regulations, such as restriction to a maximally effective dose, or the provision of information concerning dosage and potential side effects to consumers.4 One regulatory body, the European Food Safety Authority (EFSA), published an evaluation of data from several meta-analyses and provided a dosing recommendation related to the health claim of reduction of sleep onset latency. The EFSA recommends using a dose of no more than 0.3 to 1 mg of melatonin to obtain the claimed effect, noting that the relationship between melatonin and reduction of sleep latency was established in studies including such doses.6 While an optimal dose of melatonin has yet to be determined by U.S. regulatory bodies, a systematic review of the evidence in studies of older adults revealed that doses ranging from 0.5 to 6 mg had a statistically significant effect on sleep compared to placebo.3 Doses greater than 6 mg were not associated with significant sleep improvement compared to placebo.3
Studies have shown that exposure to supra-physiological plasma concentrations can lead to melatonin receptor desensitization.3,4 The range of maximally effective doses (0.3-1 mg) of exogenous melatonin was determined when the Massachusetts Institute of Technology first patented the medication. Since then, higher doses of up to 10 mg have been made available on the market. Although recent evidence suggests that doses greater than 6 mg of melatonin provide little benefit, additional research is required to determine the specific doses of melatonin that may be supra-therapeutic and subsequently interfere with the natural sleep-wake cycle or worsen insomnia from receptor desensitization.4 Appropriate monitoring and recommendations should be made to limit the dose being used on a regular basis in elderly people.3,4
In conclusion, while the efficacy of melatonin remains unclear, current evidence suggests that scheduled lower doses may improve sleep onset latency. If melatonin is preferred in a patient with an increased risk of experiencing adverse events from prescription sleep aids, lower doses may be recommended to reduce the risk of worsening insomnia.
Dr. Anna Furman received her PharmD degree from the Ohio Northern University Raabe College of Pharmacy in Ada, Ohio in 2019. During her schooling, she worked as a healthcare interpreter for the elderly Russian-speaking population and as a pharmacy intern at University Hospitals in Cleveland, Ohio. She is currently completing a PGY1 pharmacy practice residency at Tabula Rasa Healthcare in Moorestown, New Jersey with a focus in geriatric personalized medicine and targeted therapeutics.