Melatonin

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.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.Melatonin is also used to manage anxiety before and after surgery; 80% of surgical patients experience anxiety.

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 (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 patients) 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 (A meta-analysis of 19 studies (1683 patients) 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 trials 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 (). One meta-analysis of randomized trials 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 (). 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 (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 (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 including 12 randomized trials with 774 patients found 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 (A 2015 Cochrane systematic review including 12 randomized trials with 774 patients found 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 may also help diminish the behavioral symptoms associated with sundowning (Melatonin may also help diminish the behavioral symptoms associated with sundowning (9). A meta-analysis of 7 randomized trials including 462 patients with Alzheimer disease reported that melatonin may improve sleep quality in such patients (). A meta-analysis of 7 randomized trials including 462 patients with Alzheimer disease reported that melatonin may improve sleep quality in such patients (10).

Melatonin content varies in different products (Melatonin content varies in different products (11).

Headache, dizziness, nausea, sleepiness, and transient depression may occur. Melatonin may worsen existing depression. 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 adults with dementia, due to insufficient evidence (The 2015 guidelines by the American Academy of Sleep Medicine recommend against melatonin use by older adults with dementia, due to insufficient evidence (12). A report on use of melatonin in older adults suggested that overall melatonin use may be safe but the effects of long-term use are unknown (). A report on use of melatonin in older adults suggested that overall melatonin use may be safe but the effects of long-term use are unknown (13). It is important to consider that melatonin may stay active in older adults longer than in younger people and cause daytime drowsiness. Thus, more studies are needed to evaluate the safety of melatonin in older adults as well as those with dementia.). It is important to consider that melatonin may stay active in older adults longer than in younger people and cause daytime drowsiness. Thus, more studies are needed to evaluate the safety of melatonin in older adults as well as those with dementia.

Unintentional pediatric melatonin ingestion occurs because of its widespread household availability and use (Unintentional pediatric melatonin ingestion occurs because of its widespread household availability and use (14).

Evidence suggests that melatonin may increase the effects of warfarin, increasing the risk of bleeding.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 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 enhance the sedative effects of drugs such as benzodiazepines.

Melatonin may increase adverse effects of methamphetamine.Melatonin may increase adverse effects of methamphetamine.

Fluvoxamine, estrogens, and quinolone antibiotics may increase melatonin levels. Carbamazepine and rifampin may decrease melatonin levels.Fluvoxamine, estrogens, and quinolone antibiotics may increase melatonin levels. Carbamazepine and rifampin may decrease melatonin levels.

(See also table Some Possible Dietary Supplement–Medication Interactions.)

1. 1. Melatonin for jet lag. Drug Ther Bull. 58(2):21-24, 2020. doi: 10.1136/dtb.2019.000074

2. 2. Buscemi N, Vandermeer B, Pandya R, et al. Melatonin for treatment of sleep disorders. . Melatonin for treatment of sleep disorders.Evid Rep Technol Assess (Summ). (108):1-7, 2004. doi:10.1037/e439412005-001

3. 3. Ferracioli-Oda E, Qawasmi A, Bloch MH. Meta-analysis: melatonin for the treatment of primary sleep disorders. . Meta-analysis: melatonin for the treatment of primary sleep disorders.PLoS One. 8(5):e63773, 2013. doi: 10.1371/journal.pone.0063773

4. 4. Auld F, Maschauer EL, Morrison I, et al. Evidence for the efficacy of melatonin in the treatment of primary adult sleep disorders. . 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. 5. Li T, Jiang S, Han M, et al. Exogenous melatonin as a treatment for secondary sleep disorders: a systematic review and meta-analysis. . 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. 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. 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. 8. Hansen MV, Halladin NL, Rosenberg J, Gögenur I, Møller AM. Melatonin for pre- and postoperative anxiety in adults. . Melatonin for pre- and postoperative anxiety in adults.Cochrane Database Syst Rev. (4):CD009861, 2015. doi:10.1002/14651858.CD009861.pub2

9. 9. de Jonghe A, Korevaar JC, van Munster BC, de Rooij SE. Effectiveness of melatonin treatment on circadian rhythm disturbances in dementia. Are there implications for delirium? A systematic review. . Effectiveness of melatonin treatment on circadian rhythm disturbances in dementia. Are there implications for delirium? A systematic review.Int J Geriatr Psychiatry. 2010 Dec;25(12):1201-8. doi: 10.1002/gps.2454. PMID: 21086534.

10. 10. Wang YY, Zheng W, Ng CH, Ungvari GS, Wei W, Xiang YT. Meta-analysis of randomized, double-blind, placebo-controlled trials of melatonin in Alzheimer's disease.. Meta-analysis of randomized, double-blind, placebo-controlled trials of melatonin in Alzheimer's disease. Int J Geriatr Psychiatry. 2017 Jan;32(1):50-57. doi: 10.1002/gps.4571. Epub 2016 Sep 19. PMID: 27645169.

11. 11. Erland LA, Saxena PK. Melatonin natural health products and supplements: presence of serotonin and significant variability of melatonin content. . 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

12. 12. 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

13. 13. 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. . Current Insights into the Risks of Using Melatonin as a Treatment for Sleep Disorders in Older Adults.Clin Interv Aging. 2023 Jan 12;18:49-59. doi: 10.2147/CIA.S361519

14. 14. Lelak K, Vohra V, Neuman MI, et al. Pediatric melatonin ingestions - United States, 2012-2021. . Pediatric melatonin ingestions - United States, 2012-2021.MMWR Morb Mortal Wkly Rep. 71(22):725-729, 2022. doi:10.15585/mmwr.mm7122a1

The following English-language resource may be useful. Please note that The Manual is not responsible for the content of this resource.

1. National Institutes of Health (NIH), National Center for Complementary and Integrative Health: Melatonin in as a dietary supplement