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Melatonin

AEMPS

Hypnotics. Melatonin receptor agonists

ATC code: N05CH01

Brand names – drugs: Circadin, Slenyto

Brand names – supplements: Natrol Melatonin, Nature Made MelatoninSupplements are not tested in clinical trials and are not registered as medications.

Updated · Methodology

Indications

A

Jet lag disorder

First line

Melatonin is first-line for jet lag treatment and prevention. The 2002 Cochrane review (10 RCTs) showed a 50% reduction in jet lag symptoms when crossing 5 or more time zones. Dose: 0.5–5 mg 30 minutes before desired sleep in local time, for 2–5 days after arrival. 2015 recommends melatonin for jet lag with “strong” evidence. Effect is more pronounced with eastward travel.

Doses above 3 mg do not provide additional benefit. In older adults, start at 0.5–1 mg to reduce residual morning sleepiness.

Sources

  1. Cochrane: Melatonin for the prevention and treatment of jet lag (2002)
  2. ГРЛС: Мелатонин – Государственный реестр лекарственных средств (2026)

ICD-10: G47.25 · ICD-11: 7A65

B

Delayed sleep phase syndrome

First line

Melatonin in low doses (0.3–0.5 mg) 5–7 hours before desired sleep time is the main pharmacological approach to delayed sleep phase syndrome. 2015 recommends melatonin combined with morning bright-light therapy. Standard hypnotics (Z-drugs, benzodiazepines) do not help in DSPS – the problem is not sleep onset itself but a shifted internal clock. Therapy lasts weeks to months with gradual timing adjustment.

Sources

  1. AASM: Clinical Practice Guideline for the Treatment of Intrinsic Circadian Rhythm Sleep-Wake Disorders (2015)

ICD-10: G47.2 · ICD-11: 7A60

B

Insomnia in older adults

Second line

Prolonged-release melatonin (Circadin 2 mg) is -approved for short-term (up to 13 weeks) treatment of chronic insomnia in patients 55 and older. The effect is modest – sleep latency reduction by 9 minutes and improved subjective sleep quality. Used when CBT-I and standard hypnotics are contraindicated. Foundational therapy is CBT-I and sleep hygiene.

Sources

  1. EMA: Circadin (melatonin) – Summary of Product Characteristics (2023)
  2. AASM: Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults (2017)

ICD-10: G47.0 · ICD-11: 7A00

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

D

Anti-aging and longevity

Not recommended

Melatonin is a hormone that regulates the sleep-wake cycle. For anti-aging and longevity it gets promoted as a supplement that slows aging and extends lifespan. Studies have not shown a convincing benefit for this use in people – there is no solid evidence base for taking melatonin to live longer. What actually supports healthy aging is steady sleep, physical activity, good nutrition, and managing risk factors with a doctor. At usual doses melatonin is safe, but the longevity claim is unproven.

Sources

  1. AASM: Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults (2017)
D

Insomnia and sleep disorders

Not recommended

2017 recommends against melatonin for chronic insomnia in adults under 55 (weak recommendation, low evidence). Systematic reviews showed a clinically insignificant effect – sleep latency reduction by 4 minutes, sleep duration increase by 13 minutes. Foundational therapy is CBT-I; pharmacological options include doxylamine, short-course benzodiazepine receptor agonists, and orexin antagonists.

Sources

  1. AASM: Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults (2017)

ICD-10: G47.0 · ICD-11: 7A00

How to read tiers A–F
  • AStrong evidence – first or second line in international guidelines
  • BRecommended in selected cases
  • CStudy data contradict each other
  • DBenefit not proven, no documented harm
  • FDocumented harm, or risk without benefit

Mechanism of action

Melatonin is a pineal hormone that synchronises circadian rhythms with the light cycle. It binds MT1 and MT2 receptors in the suprachiasmatic nucleus of the hypothalamus. Reduces sleep latency and shifts the circadian rhythm when correctly timed. Distinct from classical hypnotics (benzodiazepines, Z-drugs) – does not cause dependence, sedative effect is minimal. Efficacy depends on individual receptor sensitivity and timing relative to the individual circadian rhythm.

Safety

Contraindications

  • Hypersensitivity to melatonin
  • Severe hepatic impairment
  • Autoimmune diseases (relative contraindication)
  • Pregnancy and breastfeeding
  • Children under 2 (all forms); under 18 outside paediatric protocols

Serious adverse effects

  • Paradoxical reactions – worsening of insomnia, increased anxiety (rare)
  • Allergic reactions (very rare)

Common adverse effects

  • Headache
  • Morning sleepiness
  • Dizziness
  • Nausea

Uncommon adverse effects

  • Vivid dreams, nightmares
  • Irritability, mood changes
  • Gastrointestinal discomfort

Pregnancy: can you take Melatonin?

Data in pregnancy are insufficient. Endogenous melatonin contributes to pregnancy physiology and foetal development. Supplemental melatonin in pregnancy is not recommended.

Breastfeeding: can you take Melatonin?

Transfers into breast milk. Use during breastfeeding is not recommended due to possible effects on infant circadian rhythm.

Calculate RIDFull profile on NIH LactMed ↗

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Practical notes

Timing and administration

Timing is critical. For insomnia and older adults: 30–60 minutes before desired sleep. For DSPS: 5–7 hours before target sleep time. For eastward jet lag: evening local time. For westward: evening local time from day 2–3. Use after midnight in people with normal circadian rhythm shifts the sleep phase and worsens sleep.

Dose titration

Standard supplement dose: 3 mg; pharmaceutical immediate-release: 1.5–3 mg (Melaxen); prolonged-release: 2 mg (Circadin). Optimal dose for most indications: 0.5–3 mg. Doses above 5 mg do not improve sleep onset but increase morning grogginess and nightmare risk. In children with ASD, the dose is individualised in a specialist service. In Spain, the AEMPS treats melatonin as a medicine when a product provides more than 2 mg a day, so food supplements there stay below 2 mg per daily dose (AESAN, 2013; Basque Government Health Department, 2013).

Monitoring

No specific monitoring is needed with short-term use. With long-term therapy (over 3 months), reassess efficacy and need for continuation. In patients on warfarin, monitor INR when adding melatonin. Individual response varies with baseline endogenous melatonin levels.

Special situations

In children, melatonin is registered in Russia only as Slenyto for children over 2 with autism spectrum disorder. Routine use in healthy children and adolescents is not recommended. In epilepsy, caution is required – seizure threshold reduction has been reported in some patients. In depression, bipolar disorder, or autoimmune disease, use is discussed with the treating clinician.

Common myths

Myth: “melatonin is a safe sleep aid for everyone”. Fact: effect on insomnia in adults under 55 is clinically insignificant. Benefit is established mainly for jet lag and DSPS. In epilepsy, on warfarin, or on immunosuppressive therapy, caution is required.

Myth: “higher dose, better effect”. Fact: doses above 3–5 mg do not improve sleep onset but increase morning grogginess and nightmare risk. Supplements at 10 mg and above are marketing, not science.

Myth: “melatonin is the youth hormone”. Fact: antioxidant and anti-ageing effects are not clinically confirmed. Long-term high-dose use in older adults has not been studied. Age-related decline in melatonin secretion is physiological, not pathological.

Drug–drug interactions

1 pair found. Sorted from critical to minor.

ModerateAshwagandha (Withania somnifera)Dietary supplements, plant adaptogens (local classification)

Mechanism

Both are taken at night and for the same reason, so they end up in the same regimen easily. Ashwagandha has sedative activity of its own and melatonin advances sleep onset; together, next-morning residual drowsiness exceeds either one alone.

Symptoms

Morning drowsiness, a foggy head, slower reactions at the wheel. In older people, a higher risk of falling when getting up at night.

Management

Try one thing at a time for two weeks before adding the other: one is almost always enough. If both are kept, start with the lower melatonin dose and avoid early-morning driving until tolerance is clear.

Sources

Pair details →Ashwagandha (Withania somnifera) →

Label mentions9 mentions

Verbatim lines from the interaction sections, in the language of the label

From this drug’s label

  • MajorFluvoxamine
    «Hay que extremar la precaución en los pacientes en tratamiento con fluvoxamina, ya que incrementa las concentraciones de melatonina (multiplica por 17 el valor de AUC y por 12 el de Cmáx) al inhibir…»

    AEMPS, section 4.5 · Open on CIMA

  • benzodiazepinasclass named in the label
    «Hay abundantes datos bibliográficos sobre el efecto de los agonistas y antagonistas adrenérgicos, los agonistas y antagonistas opiáceos, los antidepresivos, los inhibidores de las prostaglandinas…»

    AEMPS, section 4.5 · Open on CIMA

  • Carbamazepine
    «Los inductores del CYP1A2, como la carbamazepina o la rifampicina, pueden reducir la concentración plasmática de melatonina.»

    AEMPS, section 4.5 · Open on CIMA

  • depresores del SNCclass named in the label
    «Melatonina puede potenciar las propiedades sedantes de las benzodiacepinas y de los hipnóticos no benzodiacepínicos, tales como el zaleplón, el zolpidem y la zopiclona. En un ensayo clínico se…»

    AEMPS, section 4.5 · Open on CIMA

  • inhibidores del CYP1A2class named in the label
    «Los inhibidores del CYP1A2, como las quinolonas, pueden provocar aumento de la exposición a la melatonina.»

    AEMPS, section 4.5 · Open on CIMA

  • opioidesclass named in the label
    «Hay abundantes datos bibliográficos sobre el efecto de los agonistas y antagonistas adrenérgicos, los agonistas y antagonistas opiáceos, los antidepresivos, los inhibidores de las prostaglandinas…»

    AEMPS, section 4.5 · Open on CIMA

  • quinolonasclass named in the label
    «Los inhibidores del CYP1A2, como las quinolonas, pueden provocar aumento de la exposición a la melatonina.»

    AEMPS, section 4.5 · Open on CIMA

  • Rifampicin
    «Los inductores del CYP1A2, como la carbamazepina o la rifampicina, pueden reducir la concentración plasmática de melatonina.»

    AEMPS, section 4.5 · Open on CIMA

  • Zolpidem
    «Melatonina puede potenciar las propiedades sedantes de las benzodiacepinas y de los hipnóticos no benzodiacepínicos, tales como el zaleplón, el zolpidem y la zopiclona. En un ensayo clínico se…»

    AEMPS, section 4.5 · Open on CIMA

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Frequently asked

What is Melatonin used for?

Melatonin is evaluated for the following indications with varying evidence strength: Jet lag disorder (evidence tier A), Delayed sleep phase syndrome (evidence tier B), Insomnia in older adults (evidence tier B). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Melatonin?

Common side effects of Melatonin (≥ 1 in 100): Headache, Morning sleepiness, Dizziness, Nausea. See the Safety section for uncommon and serious reactions.

Is Melatonin safe during pregnancy?

Data in pregnancy are insufficient. Endogenous melatonin contributes to pregnancy physiology and foetal development. Supplemental melatonin in pregnancy is not recommended.

Is Melatonin compatible with breastfeeding?

Transfers into breast milk. Use during breastfeeding is not recommended due to possible effects on infant circadian rhythm.

Who should not take Melatonin?

Melatonin is contraindicated in: Hypersensitivity to melatonin; Severe hepatic impairment; Autoimmune diseases (relative contraindication); Pregnancy and breastfeeding; Children under 2 (all forms); under 18 outside paediatric protocols. Full list in the Safety section.

“melatonin is a safe sleep aid for everyone”

effect on insomnia in adults under 55 is clinically insignificant. Benefit is established mainly for jet lag and DSPS. In epilepsy, on warfarin, or on immunosuppressive therapy, caution is required.

“higher dose, better effect”

doses above 3–5 mg do not improve sleep onset but increase morning grogginess and nightmare risk. Supplements at 10 mg and above are marketing, not science.

“melatonin is the youth hormone”

antioxidant and anti-ageing effects are not clinically confirmed. Long-term high-dose use in older adults has not been studied. Age-related decline in melatonin secretion is physiological, not pathological.

Official sources

Direct links to regulator labels. Open in a new tab.

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