Hypnotics. Melatonin receptor agonists
ATC code: N05CH01 (Melatonin)
Brand names – drugs
Circadin, Slenyto
Brand names – supplements
Natrol Melatonin, Nature Made Melatonin
Supplements are not tested in clinical trials and are not registered as medications.
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.
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.
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.
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.
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.
Not recommended
— Anti-aging and longevity: Melatonin for slowing ageing, antioxidant protection, or extending lifespan is not mentioned in international guidelines. The antioxidant hypothesis has not been convincingly confirmed in clinical RCTs. The marketing position of “youth hormone” lacks evidence. Long-term high-dose use in older adults has not been studied and is not recommended.
Data in pregnancy are insufficient. Endogenous melatonin contributes to pregnancy physiology and foetal development. Supplemental melatonin in pregnancy is not recommended.
Transfers into breast milk. Use during breastfeeding is not recommended due to possible effects on infant circadian rhythm.
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.
Common side effects of melatonin (≥ 1 in 100): Headache, Morning sleepiness, Dizziness, Nausea. See the Safety section for uncommon and serious reactions.
FDA category C. Data in pregnancy are insufficient. Endogenous melatonin contributes to pregnancy physiology and foetal development. Supplemental melatonin in pregnancy is not recommended.
Transfers into breast milk. Use during breastfeeding is not recommended due to possible effects on infant circadian rhythm.
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.
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.
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.
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.