Melatonin
Sleep hormone supplement for jet lag and circadian rhythm sleep disorders
Melatonin is a synthetic version of the naturally occurring hormone produced by the pineal gland that helps regulate the body's sleep-wake cycle (circadian rhythm). It is prescribed for the short-term treatment of jet lag in adults and for insomnia in children and adolescents aged 6–17 with ADHD when non-pharmacological sleep hygiene measures have been insufficient. In many European countries melatonin requires a prescription, while in some regions it is available over the counter. This guide covers approved uses, dosage, side effects, drug interactions, and safety information based on international clinical guidelines.
Quick Facts
Key Takeaways
- Melatonin is a hormone-based sleep aid that works by supporting the body's natural circadian rhythm rather than sedating the brain directly.
- It is clinically proven to reduce jet lag symptoms, particularly when crossing five or more time zones in an eastward direction.
- For children aged 6–17 with ADHD, melatonin can improve sleep onset when sleep hygiene measures alone are insufficient.
- Unlike benzodiazepines and Z-drugs, melatonin does not cause physical dependence, withdrawal symptoms, or rebound insomnia.
- Common side effects include headache and drowsiness; serious reactions are rare. Use with caution in diabetes, epilepsy, autoimmune conditions, and during pregnancy.
What Is Melatonin and What Is It Used For?
Melatonin belongs to a group of compounds known as indoleamines and is naturally produced by the pineal gland, a small endocrine gland located in the centre of the brain. Under normal physiological conditions, melatonin secretion rises sharply in the evening as darkness falls, peaks during the middle of the night, and declines toward dawn. This rhythmic pattern plays a central role in signalling to the body when it is time to sleep and when to wake, forming the core of the circadian sleep-wake cycle.
Exogenous (externally administered) melatonin mimics the action of the endogenous hormone by binding to MT1 and MT2 melatonin receptors in the suprachiasmatic nucleus (SCN) of the hypothalamus, which serves as the body's master clock. By doing so, it can advance or delay the timing of sleep onset, making it therapeutically valuable in situations where the circadian rhythm has been disrupted.
Melatonin has several approved clinical indications. In adults, it is licensed for the short-term treatment of jet lag — the collection of symptoms (fatigue, insomnia, difficulty concentrating, gastrointestinal discomfort) caused by rapid travel across multiple time zones. Clinical trials and systematic reviews, including a Cochrane review, have confirmed that melatonin taken close to bedtime at the destination significantly reduces both the subjective severity and duration of jet lag, particularly after eastward flights crossing five or more time zones.
In children and adolescents aged 6 to 17 years with attention deficit hyperactivity disorder (ADHD), melatonin is approved for the treatment of insomnia when other sleep-promoting measures — such as consistent bedtime routines, limiting screen exposure, and creating a dark, quiet sleep environment — have proved insufficient. Sleep difficulties are extremely common in ADHD, affecting up to 70% of children with the condition, and chronic sleep deprivation can worsen ADHD symptoms during the day. Melatonin helps these patients fall asleep more quickly without the sedative hangover or dependency risks associated with other hypnotics.
In some countries, prolonged-release formulations of melatonin (such as Circadin 2 mg) are also licensed for the treatment of primary insomnia in adults aged 55 and older. This extended-release form is designed to mimic the natural overnight secretion pattern of melatonin, improving both sleep quality and morning alertness without causing next-day impairment.
What Should You Know Before Taking Melatonin?
Contraindications
Melatonin must not be taken by anyone who has a known allergy (hypersensitivity) to melatonin itself or to any of the excipients contained in the specific formulation. Allergic reactions are rare but can include facial swelling, swelling of the mouth or tongue, and skin rash. If any signs of a hypersensitivity reaction occur, the medication should be stopped immediately and medical attention sought.
Warnings and Precautions
Before starting melatonin, patients should discuss their full medical history with a healthcare provider. Several conditions require careful monitoring or dose adjustment when melatonin is used:
- Diabetes or impaired glucose tolerance: Melatonin can affect blood sugar regulation. Patients with diabetes should avoid eating for two hours before and two hours after taking melatonin and should monitor their blood glucose more frequently during treatment.
- Liver or kidney impairment: Melatonin is extensively metabolised in the liver, primarily by the CYP1A2 enzyme. Impaired liver function can significantly increase melatonin blood levels. Patients with renal impairment should also use melatonin with caution as clearance may be reduced.
- Autoimmune diseases: There is limited clinical data on melatonin use in patients with autoimmune conditions. Because melatonin has immunomodulatory properties, it could theoretically influence immune system activity. Patients with conditions such as rheumatoid arthritis, lupus, or multiple sclerosis should consult their doctor before use.
- Epilepsy: Melatonin may increase seizure frequency in some patients with epilepsy. While some studies suggest melatonin has anticonvulsant properties, the evidence is mixed, and patients with epilepsy should be closely monitored.
- Smoking: Tobacco smoke induces CYP1A2 activity, which can accelerate melatonin metabolism and reduce its effectiveness. Smokers may require higher doses, as determined by their prescribing physician.
- Women of childbearing potential: Contraception should be used during melatonin treatment. Note that certain oral contraceptives containing ethinylestradiol can increase melatonin blood levels (see Drug Interactions section).
Children and Adolescents
Melatonin should not be given to children or adolescents under 18 years of age for the treatment of jet lag, as efficacy and safety have not been established for this use in younger patients. For insomnia related to ADHD, melatonin should not be used in children under 6 years of age. In children aged 6 to 17 with ADHD, treatment should only be initiated after all other treatable causes of insomnia have been excluded and non-pharmacological sleep-promoting measures have been tried and found insufficient.
Pregnancy and Breastfeeding
Melatonin is not recommended during pregnancy. Melatonin crosses the placenta, and there is insufficient data to establish whether this poses a risk to the developing foetus. Animal studies have not revealed direct harmful effects, but the lack of well-controlled human studies means that the precautionary principle applies. Women who are pregnant or planning to become pregnant should not take melatonin.
Melatonin is secreted in breast milk, and the effects on a nursing infant are unknown. As a precaution, melatonin should not be used during breastfeeding. Women of childbearing potential should use effective contraception during treatment. Some oral contraceptives may interact with melatonin (see Drug Interactions).
Driving and Operating Machinery
Melatonin may cause drowsiness. If you experience this side effect, you should not drive a vehicle or operate heavy machinery. Drowsiness can impair reaction times and cognitive function, particularly in the hours immediately after taking the medication. Patients should assess their own alertness before engaging in any activity that requires sustained attention.
If you have diabetes, do not eat for 2 hours before or 2 hours after taking melatonin, as the medication may temporarily increase blood sugar levels. Monitor your glucose closely during treatment.
How Does Melatonin Interact with Other Drugs?
Melatonin is primarily metabolised by the liver enzyme CYP1A2, and to a lesser extent by CYP2C19. Any drug that inhibits or induces these enzymes can alter melatonin blood levels. Additionally, melatonin's pharmacological effects (sedation, blood pressure changes, immune modulation) can interact with the effects of other medications. Below is a summary of the most clinically significant interactions.
Major Interactions
| Drug / Class | Effect on Melatonin | Clinical Advice |
|---|---|---|
| Fluvoxamine (SSRI antidepressant) | Potent CYP1A2 inhibitor; can increase melatonin levels up to 17-fold | Combination should generally be avoided; if co-prescribed, substantial dose reduction required |
| Ciprofloxacin (fluoroquinolone antibiotic) | Strong CYP1A2 inhibitor; significantly raises melatonin levels | Monitor for excessive sedation; consider dose reduction during antibiotic course |
| Carbamazepine, Phenytoin (antiepileptics) | CYP1A2 inducers; reduce melatonin levels | Melatonin may be less effective; dose increase may be needed under medical supervision |
| Rifampicin (antitubercular) | Potent CYP enzyme inducer; substantially reduces melatonin levels | Melatonin may be ineffective during rifampicin treatment |
| Warfarin (anticoagulant) | Melatonin may alter anticoagulant effect | INR should be monitored more frequently if melatonin is started or stopped |
Other Notable Interactions
| Drug / Class | Effect | Clinical Advice |
|---|---|---|
| Citalopram (SSRI) | Mild CYP1A2 inhibition; modest increase in melatonin levels | Usually well tolerated; monitor for increased drowsiness |
| Zolpidem (Z-drug hypnotic) | Additive sedation; enhanced next-day impairment | Avoid concurrent use unless directed by physician |
| Cimetidine, Omeprazole (acid suppressants) | CYP1A2 / CYP2C19 inhibition; may increase melatonin levels | Monitor for increased drowsiness |
| Nifedipine, Verapamil, Beta-blockers | Potential additive blood pressure lowering; beta-blockers may reduce endogenous melatonin | Monitor blood pressure; discuss timing with physician |
| Oral contraceptives (ethinylestradiol/gestagen) | CYP1A2 inhibition; may increase endogenous and exogenous melatonin levels | Lower melatonin doses may be sufficient |
| NSAIDs (ibuprofen, aspirin) | May reduce endogenous melatonin production | Avoid evening NSAID use if possible during melatonin therapy |
| Caffeine | CYP1A2 substrate; may compete for metabolism | Avoid caffeine in the evening; it may reduce melatonin effectiveness |
Melatonin and Alcohol
Alcohol should not be consumed when taking melatonin. Alcohol reduces the efficacy of melatonin by interfering with the hormone's ability to promote sleep onset and maintain sleep architecture. Alcohol also disrupts the later stages of sleep, reducing REM sleep and increasing nighttime awakenings. The combination of melatonin with alcohol may also intensify drowsiness and impair cognitive function, making activities such as driving more dangerous.
What Is the Correct Dosage of Melatonin?
Melatonin dosing varies significantly depending on the indication, the patient's age, and the specific formulation prescribed. It is essential to follow the prescribing physician's instructions. The dosages below represent general guidelines based on approved product labelling and clinical evidence.
Adults — Jet Lag
Jet Lag (Adults 18+)
Starting dose: 3 mg once daily
Dose range: 0.5 mg to 5 mg, adjusted gradually to find the lowest effective dose
Duration: Maximum 5 days per treatment episode
- Take the first dose on arrival at the destination at your normal bedtime
- Continue taking melatonin at the same time each subsequent evening
- Do not take before 8:00 PM or after 4:00 AM
- Maximum 16 treatment episodes per year
Children and Adolescents — Insomnia with ADHD
Insomnia in Children (6–17 years) with ADHD
Starting dose: 0.5 mg to 2 mg once daily
Maximum dose: 5 mg daily (regardless of age)
Timing: 30 to 60 minutes before bedtime
- Dose is individually adjusted to the lowest effective level
- Treatment should be reviewed by a physician at least every 6 months
- An annual treatment break is recommended to assess whether melatonin is still needed
- All other treatable causes of insomnia must be excluded before starting
Elderly Adults — Primary Insomnia
Primary Insomnia (Adults 55+) — Prolonged-release formulation
Dose: 2 mg once daily (prolonged-release tablet, e.g. Circadin)
Timing: 1 to 2 hours before bedtime, after food
Duration: Up to 13 weeks; longer-term use under medical supervision
- Swallow the tablet whole — do not crush or chew (prolonged-release formulation)
- Clinical studies have shown improved sleep quality and morning alertness in this age group
Special Note for Patients with Diabetes
If you or your child has diabetes or impaired glucose tolerance, do not consume food for 2 hours before or 2 hours after taking melatonin. This precaution is necessary because melatonin can temporarily increase blood sugar levels. Blood glucose should be monitored more frequently during melatonin treatment.
How to Take Melatonin
Tablets should be swallowed with water. Immediate-release tablets may be crushed and mixed with water immediately before taking, which can be helpful for children or patients who have difficulty swallowing. However, prolonged-release tablets (such as Circadin) must be swallowed whole to maintain their slow-release properties. Oral solution should be measured with the provided dosing syringe.
Food should not be consumed for 2 hours before or 2 hours after taking melatonin, as food can affect absorption and blood sugar response.
Missed Dose
If you forget to take your dose at bedtime and wake during the night, you may take the missed dose, but not after 4:00 AM. Do not take a double dose to compensate for a missed one. If it is close to your normal waking time, simply skip the missed dose and resume your normal dosing schedule the following evening.
Overdose
If you take more than the recommended dose, or if a child accidentally ingests melatonin, contact a doctor, hospital, or poison control centre immediately for assessment and advice. Symptoms of overdose may include excessive drowsiness, headache, dizziness, and nausea. There is no specific antidote; treatment is supportive.
Stopping Melatonin
There are no known harmful effects from stopping melatonin treatment. Unlike many other sleep medications, melatonin does not cause dependence, and there are no reported withdrawal symptoms or rebound insomnia upon discontinuation. Treatment can be stopped at any time without the need for gradual dose reduction (tapering).
What Are the Side Effects of Melatonin?
Like all medicines, melatonin can cause side effects, although not everyone experiences them. The side effects listed below are classified according to their frequency of occurrence, based on clinical trial data and post-marketing surveillance reports. Most side effects are mild and tend to resolve on their own.
Stop taking melatonin and seek emergency medical care if you experience: swelling of the face, mouth or tongue (angioedema), severe skin reactions, or chest pain. These are rare but potentially serious reactions.
Common
May affect up to 1 in 10 people
- Headache
- Drowsiness / sleepiness
Uncommon
May affect up to 1 in 100 people
- Irritability, nervousness, restlessness, anxiety
- Insomnia, abnormal dreams, nightmares
- Migraine, dizziness, lethargy
- High blood pressure
- Abdominal pain, nausea, dry mouth, mouth ulcers
- Skin inflammation, itching, rash, dry skin, night sweats
- Pain in arms or legs
- Feeling of weakness, chest discomfort
- Weight gain
- Abnormal liver function tests
Rare
May affect up to 1 in 1,000 people
- Shingles (herpes zoster reactivation)
- Reduced white blood cell or platelet count
- Low calcium or sodium levels in the blood
- Elevated blood lipids (cholesterol/triglycerides)
- Mood changes, aggression, tearfulness, disorientation
- Fainting, memory impairment, restless legs syndrome
- Blurred vision, increased tear production
- Vertigo, palpitations, hot flushes
- Acid reflux, vomiting, flatulence, increased salivation
- Eczema, psoriasis, nail disorders
- Joint inflammation, muscle cramps, neck pain
- Increased urination, blood in urine
- Prolonged erection (priapism) unrelated to sexual stimulation
- Fatigue, thirst, abnormal blood electrolytes
Frequency Not Known
Reported post-marketing; frequency cannot be estimated
- Hypersensitivity reaction (angioedema — swelling of face, mouth, tongue)
- Abnormal breast milk production (galactorrhoea)
- Hallucinations (visual, auditory, or tactile)
- Hyperglycaemia (elevated blood sugar)
Reporting Side Effects
Reporting suspected side effects after a medicine has been authorised is important for ongoing safety monitoring. Healthcare professionals and patients are encouraged to report any suspected adverse reactions to their national pharmacovigilance authority — for example, the EMA in Europe, the FDA MedWatch programme in the United States, or the MHRA Yellow Card Scheme in the United Kingdom.
How Should You Store Melatonin?
Keep melatonin out of the sight and reach of children at all times. Store in the original packaging to protect from light, as melatonin is photosensitive and can degrade when exposed to light over prolonged periods. No special temperature conditions are required — standard room temperature storage is appropriate for most formulations.
Do not use melatonin after the expiry date stated on the packaging (marked EXP). The expiry date refers to the last day of the stated month. After opening oral solution bottles, check the product leaflet for any specific in-use shelf life.
Unused or expired medicines should not be disposed of via household waste or down the drain. Return them to a pharmacy for proper disposal in accordance with local regulations. This helps to protect the environment and prevents accidental ingestion.
What Does Melatonin Contain?
Melatonin tablets are available in multiple strengths: 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg, and 5 mg. The oral solution formulation contains 1 mg/ml of melatonin. Each formulation contains the active substance melatonin along with various excipients that serve as fillers, binders, and disintegrants to ensure consistent drug delivery.
Typical Inactive Ingredients (Tablet Formulations)
- Microcrystalline cellulose (E 460): A common pharmaceutical filler and binder
- Mannitol (E 421): A sugar alcohol used as a bulking agent
- Colloidal anhydrous silica (E 551): A flow agent that prevents clumping
- Croscarmellose sodium (E 468): A disintegrant that helps the tablet break apart in the stomach
- Magnesium stearate (E 470b): A lubricant used during tablet manufacturing
Prolonged-release formulations (such as Circadin) may contain additional excipients including ammonio methacrylate copolymer, calcium hydrogen phosphate dihydrate, lactose monohydrate, and talc. Patients with known lactose intolerance should check the specific product leaflet for their prescribed brand.
Melatonin tablets contain less than 1 mmol (23 mg) of sodium per tablet, meaning they are essentially sodium-free. This is relevant for patients on sodium-restricted diets.
Appearance
Immediate-release tablets are typically white to off-white, round, biconvex tablets marked with their respective strength ("0.5", "1", "2", "3") on one side, with a diameter of approximately 8 mm. They are supplied in plastic containers with either tamper-evident closures or child-resistant caps, in pack sizes of 30 or 100 tablets. Not all pack sizes may be marketed in all countries.
Frequently Asked Questions About Melatonin
For adults, prolonged-release melatonin (such as Circadin 2 mg) has been studied in clinical trials lasting up to 12 months with a favourable safety profile and no evidence of dependence, tolerance, or withdrawal effects. For short-acting melatonin used for jet lag, treatment should not exceed 5 consecutive days per episode, with a maximum of 16 episodes per year. In children with ADHD-related insomnia, ongoing treatment should be reviewed by a doctor at least every 6 months, with annual treatment breaks to assess whether melatonin is still needed. Always follow your prescriber's guidance on treatment duration.
Melatonin is licensed for children and adolescents aged 6 to 17 years with ADHD who have insomnia that has not improved with sleep hygiene measures alone. The starting dose is typically 0.5 mg to 2 mg, taken 30 to 60 minutes before bedtime, with a maximum daily dose of 5 mg regardless of age or weight. Melatonin should not be given to children under 6 years for any indication, and its use for jet lag in patients under 18 has not been studied sufficiently. Paediatric formulations such as oral solutions and mini-tablets (e.g. Slenyto) are available to facilitate accurate dosing in younger patients.
No. Unlike many conventional sleep medications such as benzodiazepines (e.g. diazepam, temazepam) and Z-drugs (e.g. zolpidem, zopiclone), melatonin does not appear to cause physical dependence or tolerance with prolonged use. Clinical studies have consistently shown that stopping melatonin does not lead to rebound insomnia, withdrawal symptoms, or any deterioration in sleep quality beyond pre-treatment levels. This safety profile is one of the key advantages of melatonin over other hypnotics, particularly for use in children and older adults.
Melatonin is fundamentally different from most other sleep medications because it works by supporting the body's natural circadian rhythm rather than by directly sedating the central nervous system. Traditional hypnotics such as benzodiazepines and Z-drugs work by enhancing GABA activity in the brain, producing sedation, muscle relaxation, and amnesia — along with risks of dependence and cognitive impairment. Melatonin, in contrast, acts on specific MT1 and MT2 receptors to signal “sleep time” to the body. It generally causes fewer next-day impairment effects and does not carry a dependence risk. However, it may be less immediately effective for severe acute insomnia compared to potent sedative-hypnotics.
You should avoid drinking alcohol when taking melatonin. Alcohol reduces the effectiveness of melatonin and impairs its ability to regulate sleep onset. Furthermore, alcohol independently disrupts sleep architecture by reducing REM sleep, increasing nighttime awakenings, and fragmenting sleep stages — all of which counteract the benefits of melatonin therapy. The combination of alcohol and melatonin can also intensify drowsiness, impair coordination, and reduce cognitive function, making it unsafe to drive or operate machinery.
Yes, melatonin is one of the most extensively studied treatments for jet lag. A Cochrane systematic review of 10 randomised controlled trials found that melatonin taken close to the target bedtime at the destination (between 10:00 PM and midnight) significantly reduces the subjective severity of jet lag symptoms. The benefit is most pronounced when crossing five or more time zones, particularly in the eastward direction. Doses of 0.5 mg to 5 mg are similarly effective, although higher doses (3–5 mg) tend to promote faster sleep onset. Taking melatonin at the wrong time (e.g. during the day) can delay circadian adaptation rather than promote it.
References
This article is based on the following peer-reviewed sources and international clinical guidelines:
- Herxheimer A, Petrie KJ. Melatonin for the prevention and treatment of jet lag. Cochrane Database of Systematic Reviews. 2002;(2):CD001520. Updated 2023. DOI: 10.1002/14651858.CD001520.pub2
- European Medicines Agency (EMA). Circadin (melatonin) — Summary of Product Characteristics. EMA/HMPC. Last updated 2024.
- National Institute for Health and Care Excellence (NICE). Melatonin for sleep disorders in children and young people. Evidence summary. NICE, 2023.
- Auld F, Maschauer EL, Morrison I, Skene DJ, Riha RL. Evidence for the efficacy of melatonin in the treatment of primary adult insomnia. Sleep Medicine Reviews. 2017;34:10–22.
- Kennaway DJ. A critical review of melatonin assays: Past and present. Journal of Pineal Research. 2019;67(1):e12572.
- World Health Organization (WHO). WHO Model List of Essential Medicines. 23rd List, 2023.
- British National Formulary (BNF). Melatonin. NICE Evidence Services, 2024.
- U.S. Food and Drug Administration (FDA). Dietary Supplements: Melatonin. Consumer information, 2024.
- Ferracioli-Oda E, Qawasmi A, Bloch MH. Meta-analysis: melatonin for the treatment of primary sleep disorders. PLoS ONE. 2013;8(5):e63773.
- American Academy of Sleep Medicine (AASM). Clinical Practice Guideline for the Treatment of Intrinsic Circadian Rhythm Sleep-Wake Disorders. Journal of Clinical Sleep Medicine. 2015;11(10):1199–1236.
Editorial Team
Written by the iMedic Medical Editorial Team — specialists in clinical pharmacology, sleep medicine, and paediatric neurology with extensive clinical and academic experience.
Reviewed by the iMedic Medical Review Board — an independent panel of physicians who verify that all content meets current international guidelines (WHO, EMA, FDA, BNF, AASM).
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