Melatonin, a hormone produced by the pineal gland, regulates circadian rhythms. It can be derived from animals, but most melatonin is manufactured synthetically. In some countries, melatonin is considered a drug and is regulated as such.
(See also Overview of Dietary Supplements and National Institutes of Health (NIH): Melatonin.)
Claims
Melatonin is used for the short-term regulation of sleep patterns, including jet lag and insomnia. Research into the use of melatonin supplementation for people affected by seasonal affective disorder, regulation of sleep patterns in people who work late shifts, and the resynchronization of the sleep/wake cycle in people with early Alzheimer disease is currently being evaluated.
Standard dosage is not established and ranges from 0.5 to 5 mg orally taken 1 hour before usual bedtime on the day of travel and 2 to 4 nights after arrival.
Melatonin is also used to manage anxiety before and after surgery; 80% of surgical patients experience anxiety.
Evidence
Some scientific evidence supports use of melatonin to minimize the effects of jet lag, especially in people traveling eastward over 2 to 5 time zones (1-2).
A meta-analysis of 19 studies (1683 subjects) found that in children and adults melatonin for treatment of primary sleep disorders decreases time to fall asleep by 7 minutes, increases overall sleep time by 8 minutes, and improves sleep quality (3). One meta-analysis of randomized controlled studies has provided evidence that melatonin decreases sleep onset latency in primary insomnia, benefits patients with delayed sleep phase syndrome, and helps regulate sleep-wake patterns in blind patients (4). Another meta-analysis found that melatonin provides benefit for secondary sleep disorders (secondary insomnia caused by sleep restriction)—specifically it reduces sleep onset latency and increases total sleep time, although it does not improve sleep efficiency (5).
A Cochrane systematic review of pharmacological interventions for sleepiness and sleep disturbances caused by shift work found low quality evidence that melatonin (1 to 10 mg) after the night shift may increase sleep length during daytime sleep by 24 minutes and night-time sleep by 17 minutes, compared to placebo (6).
Evidence supporting use of melatonin as a sleep aid in adults and children with neuropsychiatric disorders (eg, pervasive developmental disorders) is less strong. However, in 19 randomized controlled studies, melatonin significantly improved sleep onset latency, sleep duration, and wake time after sleep onset in children with neurodevelopmental disorders (7).
A 2015 Cochrane systematic review included 12 studies that involved 774 people. The review found strong evidence that melatonin is better than placebo at reducing anxiety before surgery. However, the results on melatonin’s benefits for reducing anxiety after surgery were mixed (8).
Melatonin content varies in different products (9).
Adverse Effects
Headache, dizziness, nausea, sleepiness, and transient depression may occur. Melatonin may worsen existing depression.
The 2015 guidelines by the American Academy of Sleep Medicine recommend against melatonin use by older people with dementia (10). Melatonin may stay active in older people longer than in younger people and cause daytime drowsiness.
A potential adverse effect is unintentional pediatric melatonin ingestion because of its widespread household availability and use (11).
Drug Interactions
Evidence suggests that melatonin may increase the effects of warfarin, increasing the risk of bleeding.
Melatonin may decrease the effects of antiseizure medications and increase the risk of seizures.
Melatonin may enhance the sedative effects of drugs such as benzodiazepines.
Melatonin may increase adverse effects of methamphetamine.
Fluvoxamine, estrogens, and quinolone antibiotics may increase melatonin levels. Carbamazepine and rifampin may decrease melatonin levels.
(See also table Some Possible Dietary Supplement–Drug Interactions.)
References
1. Melatonin for jet lag. Drug Ther Bull 58(2):21-24, 2020. doi: 10.1136/dtb.2019.000074
2. Buscemi N, Vandermeer B, Pandya R, et al: Melatonin for treatment of sleep disorders.Evid Rep Technol Assess (Summ) (108):1-7, 2004. doi:10.1037/e439412005-001
3. Ferracioli-Oda E, Qawasmi A, Bloch MH: Meta-analysis: melatonin for the treatment of primary sleep disorders.PLoS One 8(5):e63773, 2013. doi: 10.1371/journal.pone.0063773
4. Auld F, Maschauer EL, Morrison I, et al: Evidence for the efficacy of melatonin in the treatment of primary adult sleep disorders.Sleep Med Rev 34:10-22, 2017. doi: 10.1016/j.smrv.2016.06.005
5. Li T, Jiang S, Han M, et al: Exogenous melatonin as a treatment for secondary sleep disorders: a systematic review and meta-analysis.Front Neuroendocrinol 52:22-28, 2019. doi: 10.1016/j.yfrne.2018.06.004
6. Liira J, Verbeek JH, Costa G, et al. Pharmacological interventions for sleepiness and sleep disturbances caused by shift work. Cochrane Database Syst Rev (8):CD009776, 2014. doi:10.1002/14651858.CD009776.pub2
7. McDonagh MS, Holmes R, Hsu F: Pharmacologic treatments for sleep disorders in children: a systematic review. J Child Neurol 34(5):237-247, 2019. doi: 10.1177/0883073818821030
8. Hansen MV, Halladin NL, Rosenberg J, Gögenur I, Møller AM. Melatonin for pre- and postoperative anxiety in adults.Cochrane Database Syst Rev (4):CD009861, 2015. doi:10.1002/14651858.CD009861.pub2
9. Erland LA, Saxena PK. Melatonin natural health products and supplements: presence of serotonin and significant variability of melatonin content.J Clin Sleep Med 13(2):275-281, 2017. doi:10.5664/jcsm.6462
10. Auger RR, Burgess HJ, Emens JS, Deriy LV, Thomas SM, Sharkey KM. Clinical Practice Guideline for the Treatment of Intrinsic Circadian Rhythm Sleep-Wake Disorders: Advanced Sleep-Wake Phase Disorder (ASWPD), Delayed Sleep-Wake Phase Disorder (DSWPD), Non-24-Hour Sleep-Wake Rhythm Disorder (N24SWD), and Irregular Sleep-Wake Rhythm Disorder (ISWRD). An Update for 2015: An American Academy of Sleep Medicine Clinical Practice Guideline. J Clin Sleep Med 11(10):1199-1236, 2015 doi:10.5664/jcsm.5100
11. Lelak K, Vohra V, Neuman MI, et al: Pediatric melatonin ingestions - United States, 2012-2021.MMWR Morb Mortal Wkly Rep 71(22):725-729, 2022. doi:10.15585/mmwr.mm7122a1
More Information
The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.
National Institutes of Health (NIH), National Center for Complementary and Integrative Health:General information on the use of melatonin as a dietary supplement
