Melatonin harms

What are the most common side effects of melatonin?

In the clinical studies summarized in the EMA product information for the 2 mg prolonged-release product, 1,931 patients received melatonin and 1,642 received placebo. Of those taking melatonin, 48.8%, and of those taking placebo, 37.8%, reported at least one adverse reaction; the rate of adverse reactions per 100 patient-weeks was found to be 5.743 for placebo and 3.013 for melatonin. The most frequently reported reactions (headache, nasopharyngitis, back pain, arthralgia) occurred in both the melatonin and placebo groups. ^[1]

The adverse reaction list of the same document also names conditions such as restlessness, insomnia, abnormal dreams, nightmares, anxiety, migraine, dizziness, drowsiness, hypertension, abdominal pain, nausea and dry mouth; the frequency classes are given separately in the list, and only those seen in the clinical study at a frequency not lower than placebo, together with post-marketing spontaneous reports, were included in the list. ^[1]

The Cochrane review on jet lag also found the frequency of other side effects to be low and noted a risk of sleepiness when taken at the wrong time (early in the day). ^[4]

Drowsiness and driving: The EMA states that the product may cause drowsiness and has a moderate effect on the ability to drive and use machines, and that it should be used with care in situations where drowsiness could pose a safety risk. The Turkish SmPC (KÜB) does not recommend use before driving or operating machinery. ^{[1] [2]}

Which drugs does melatonin interact with?

Melatonin metabolism proceeds mainly through the CYP1A enzymes in the liver; drugs affecting these enzymes can change melatonin levels. The summary below is compiled from the two product information documents; interaction studies were conducted only in adults. ^{[1] [2]}

This list is taken from the interaction sections of two product information documents and is not a complete interaction check. For drug groups not mentioned in these two product information documents, such as immunosuppressants, these documents contain no information; “no interaction reported” is not the same as “no interaction.” In a person who uses regular medicines, the addition of melatonin is assessed by a physician or pharmacist together with the medicine list.

In whom is melatonin not recommended or is caution needed?

• Pregnancy and those planning pregnancy: The EMA does not recommend use because there are no clinical data on exposure during pregnancy. The Turkish SmPC states that there are insufficient data, gives the pregnancy category as C, and states that use is not recommended in those planning pregnancy and that it should not be used during breastfeeding. ^{[1] [2]}
• Breastfeeding: The EMA notes that endogenous melatonin has been measured in breast milk and that externally taken melatonin probably also passes into milk, and does not recommend breastfeeding during treatment. ^[1]
• Epilepsy and seizures: The SmPC states that melatonin may increase seizure frequency in patients who have seizures and may trigger the development of seizures in children and adolescents with multiple neurological deficits. The Cochrane jet lag review also points to case reports of harm in people with epilepsy. ^{[2] [4]}
• Autoimmune diseases: Both the EMA and the SmPC state that there are no clinical data in people with autoimmune disease and do not recommend use. ^{[1] [2]}
• Liver and kidney failure: The EMA does not recommend use in liver failure; it asks for caution in kidney failure, noting that the effect has not been studied. The SmPC states that melatonin is not recommended in severe kidney failure and in liver failure. ^{[1] [2]}
• Cardiovascular disease and users of antihypertensives: The SmPC states that there are limited data suggesting melatonin may cause adverse effects on blood pressure and heart rate, that it is unclear whether this effect arises from melatonin or from drug interaction, and does not recommend use in these people. ^[2]
• Children and adolescents: The SmPC states that long-term use may adversely affect blood glucose control, pubertal development and sexual maturation. The evidence and discussion in children are on a separate page.

What do high doses and overdose do?

The EMA and the SmPC state that doses of melatonin up to 300 mg daily have been reported in the literature to have been given without clinically significant adverse reactions, that drowsiness is expected in overdose and that the active substance is expected to be eliminated within about 12 hours of ingestion; no specific treatment is stated to be required. The EMA also states that the 2 mg product was given in clinical studies at daily doses of 5 mg for 12 months and that this did not significantly change the nature of adverse reactions. ^{[1] [2]}

In the systematic review examining doses of 10 mg and above in adults (79 randomized trials, 3,861 participants; over 30), 29 of the studies (37%) made no mention of the presence or absence of adverse events and only four met the criteria for low risk of bias. In this small subset, melatonin did not cause a detectable increase in serious adverse events (odds ratio 0.88; 95% CI 0.52–1.50) or in discontinuation because of adverse events (0.93; 0.24–3.56); however, adverse events such as drowsiness, headache and dizziness increased (1.40; 1.15–1.69). The authors state that safety reporting was limited and that the confidence intervals are wide because of the scarcity of data. ^[3]

That is, the statement “no serious harm was seen at high doses” rests on low-quality and incompletely reported data; this is not proof that high doses are safe.

Is melatonin addictive, and what happens on stopping?

The EMA product information contains two observations: in an outpatient study with 3 weeks of treatment and a 2-week placebo withdrawal period, sleep variables returned gradually to baseline “without rebound, increase in adverse reactions and increase in withdrawal symptoms.” In another study lasting up to six months, no withdrawal symptoms and no rebound insomnia were seen; the benefit was maintained up to month 3 and the primary analysis failed at month 6. ^[1]

These data belong to weeks-to-months use of the licensed product; the study durations are not sufficient to answer whether dependence or tolerance develops with use lasting years and at high doses. The statement “it is not addictive” should therefore be read as limited by study duration and dose.

Is the safety of long-term use known?

For licensed products the duration is limited: the recommended duration of use for the EMA product is up to 13 weeks; in the SmPC of the 3 mg tablet licensed in Türkiye, use for jet lag is at most 5–7 days depending on the destination. ^{[1] [2]} Continuous use beyond these durations (for example every night for years) has no licensing basis; the longest observation is the administration of the 5 mg daily dose in clinical studies for up to 12 months, as stated by the EMA. The Menczel Schrire review also emphasizes the need for better safety reporting. ^[3]

Why does accidental ingestion in children matter?

In the analysis by Lelak and colleagues of the US National Poison Data System, 260,435 isolated melatonin exposures in people aged 19 and under were reported between 2012 and 2021; the annual number increased by 530% and its share among all reports of ingestion by children rose from 0.6% in 2012 to 4.9% in 2021. Of the exposures, 83.8% were in children aged 5 and under and 94.3% were unintentional. Of 27,795 cases managed at a health care facility, 4,097 (14.7%) were hospitalized and 287 were admitted to intensive care; five children required mechanical ventilation and two deaths were reported (the relation of the deaths to melatonin was classified as “unknown” in the system). Most children had a minor effect or no effect (30.1% no effect, 67.8% minor effect). ^[5]

The MMWR erratum of July 8, 2022 corrected the sentence “84.4% of children were asymptomatic” and some rows in the table; the numbers above are taken from the corrected table. Because melatonin is regulated as a supplement in the US, these data cannot be applied directly to the context of licensed medicines in Türkiye; however, they show the risk of accidental ingestion for any melatonin product kept where children can reach it. ^[5]

Is product quality a safety problem?

In the analysis by Erland and Saxena, the melatonin amount in products sold as supplements varied between −83% and +478% of the label value, the difference between batches of the same product reached 465%, and serotonin was detected in eight products. That the amount on the label is not the amount actually taken makes both the effect and the risk of side effects unpredictable. ^[6] The legal basis and status details for why melatonin has not been permitted to be sold as a supplement in Türkiye since June 9, 2025 are described on the main page.

This guide does not recommend personal doses or medicine intervals; the product information and the opinion of a physician or pharmacist take priority.