The dietary supplement melatonin is an over-the-counter, nonprescription sleep aid for adults and children. The number of reported adult overdoses and pediatric ingestions has increased by 530 percent over the past 10 years, according to the Centers for Disease Control and Prevention.
It is generally a safe drug, but an ingestion by a child can result in hospitalization and serious complications, especially in those under age 5. The CDC recently examined melatonin, finding that the largest increase in ingestions and hospitalizations in children occurred during the COVID- 19 pandemic.
Pediatric Melatonin Ingestions-United States, 2012-2021
Lelak K, et al.
MMWR Morb Mortal Wkly Rep.
The authors of this CDC report looked at 260,435 ingestions by children to highlight the increasing number of overdoses in children over the past 10 years. A review of 12 meta-analyses concluded that melatonin results in a statistically significant but small improvement in sleep latency and total sleep time, with a lack of consensus on whether the effects are clinically meaningful. (J Psychiatrist Res. 2020;121:10.)
Melatonin is an endogenous neurohormone that regulates the sleep-wake cycle. Produced by the pineal gland in the evening in response to decreased light, endogenous melatonin is an agonist at CNS melatonin receptors that facilitates sleep. Commercially available, immediate-release melatonin supplements this action. The plasma level of melatonin peaks within approximately one hour of administration, and it should be taken close to bedtime.
Melatonin is used for insomnia in adults and for primary sleep disorders in children. A number of synthetic melatonin preparations are widely available OTC, but the concentration and purity of the ingredients are not guaranteed. Annual sales increased from $285 million in 2016 to $821 million in 2020.
Use is widespread, and melatonin has become the most frequently reported ingested substance among children to poison control centers. (Clinic Toxicol [Phila]. 2021;59:1282; https://bit.ly/3961XbS.) Nonetheless, the toxicity and outcomes of pediatric ingestions are still a bit vague.
The CDC assessed isolated melatonin ingestions in patients 19 and under based on the American Association of Poison Control Centers’ National Poison Data System. Melatonin accounted for 4.9 percent of all pediatric ingestions in 2021 compared with only 0.6 percent in 2012. Five children required mechanical ventilation, and two died.
The majority of ingestions were not associated with significant pathology, and 83 percent of the children were asymptomatic. Most ingestions were unintentional and involved boys under age 5, and 88 percent were managed outside of a health care facility. Most hospitalized patients were teenagers with intentional ingestions. Seventy-two percent of those treated at a health care facility were discharged, 15 percent were hospitalized, and one percent required intensive care. A total of 1.6 percent of all ingestions resulted in a serious outcome. The two children who died were 3 months and 13 months old. No details about these patients were presented, and the authors did not explain how the 3-month-old child received melatonin.
Melatonin is available in tablets, capsules, liquid, and gummies. The candy-like gummy would certainly be quite attractive to children. The COVID-19 pandemic probably increased the availability and accessibility of the supplement in the home. No child-resistant packaging is available.
Comments: It is not widely known, but sleep problems are reported in 25 percent of children and adolescents. I was amazed at the extent of sleep problems in children and the widespread use of melatonin. I was similarly amazed at the lack of regulation of melatonin. Adults are well known to experience sleep disorders, but a similar problem in children was a revelation to me. The first intervention for insomnia is cognitive behavioral therapy, with evidence showing effects stronger than those of medications, but this intervention is often forgotten in real life in favor of medications.
Melatonin is widely used in adults as a sleep aid despite minimal evidence. It also has antioxidant and anti-inflammatory properties and potential value in multiple diseases. Trends in melatonin use have only recently been studied (JAMA. 2022;327:483; https://bit.ly/3xdk5bH), and data on long-term and high-dose use are scarce.
Insomnia is one of the most common reasons adults seek medical advice. The ability to fall asleep at a desired time and maintain sleep without excessive waking is fragile and influenced by multiple factors.
Evaluating sleep disorders is complex and cannot be accomplished in an emergency department. Suggesting melatonin as a short-term fix for seemingly benign sleep trouble is appropriate, but a proper evaluation should be performed before prescribing medications. The short-term use of OTC sleep aids is reasonable for the emergency physician to suggest, but all individuals should receive a more complete evaluation before being started on long-term prescription sleep aids.
I would not prescribe strong sleep medications such as zolpidem, benzodiazepines, or other prescription sleep aids in the ED, although many physicians readily do so. A proper evaluation often entails a formal sleep study and some form of cognitive behavioral therapy. Most physicians try to eliminate obvious causes, and will simply prescribe or suggest a sleeping pill if none is found.
Of course, many patients embark on their own to buy sleeping pills, and multiple OTC products are available. Insomnia can be precipitated by pain, nocturia, or shortness of breath, and these are unlikely to improve with a sleeping pill. Obstructive sleep apnea is a common cause of sleep disturbance, and a sleeping pill can make this worse. The side effects of medications (opioids, stimulants, corticosteroids, antidepressants) are commonly overlooked as a cause of insomnia. Approximately half of patients with chronic insomnia have a psychiatric disorder, and the majority of those with a psychiatric disorder have insomnia.
Evaluating sleep problems can be a bit mind-boggling. The list of medications used to treat insomnia is likewise formidable. Many parents and individuals simply go to the drug store, read a few labels, and make their decision on what drug to use without much thinking. Melatonin is often the first choice because of clever advertising and word of mouth. No medications are approved by the FDA for children under 16 years old, so any medication is essentially used off-label.
Recommended doses are 1-2 mg in preschool children, 2-3 mg in school-aged children, and 5-10 mg in adolescents. Melatonin available in the drug store has a wide range of actual melatonin content, often nowhere near the information on the bottle. The melatonin content in one study varied from -83 to +478 percent of the label content. (J Clin Sleep Med. 2017;13:275; https://bit.ly/3zxHiIi.) It is generally considered safe, however, and its use for up to four years has failed to demonstrate significant adverse effects.
Most studies show that short-term melatonin use is safe even for children over 5 years old with few or no side effects. Adverse effects of melatonin are generally mild, consisting primarily of dizziness, headache, nausea, irritability, diarrhea, joint pain, and sleepiness. Significant toxicity is rare even in large doses, and it is difficult to find a fatality secondary to melatonin ingestion. The physician’s approach to a melatonin overdose should be conservative, and should not include oral charcoal or gastric emptying.
Little empirical evidence exists, however, about the efficacy, safety, and tolerability of these medications, especially in children. Melatonin is generally considered safe and effective for managing insomnia, but its use is based on relatively weak evidence, and additional research is clearly needed.
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dr Robertsis a professor of emergency medicine and toxicology at the Drexel University College of Medicine in Philadelphia. Read his past columns athttp://bit.ly/EMN-InFocus.
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