II. Indications

III. Physiology

  1. Pineal gland synthesizes Melatonin
    1. Overall Pathway: Tryptophan to Serotonin to Melatonin
    2. May also affect adrenal and gonadal function
  2. Endogenous Melatonin physiology
    1. Secreted at night
    2. Normally highest levels during sleep
      1. Increases rapidly late evening
      2. Peaks after midnight
      3. Decreases in Morning
  3. Potential Effects on Sleep
    1. Improved Sleep Efficiency (Sleep Time/Time in bed)
    2. Decreased Nocturnal Awakenings
    3. Improved Sleep quality
    4. Does not Decrease sleep latency
    5. Does not Increase total sleep time
  4. As compared with Benzodiazepines
    1. Not addictive
    2. Does not suppress REM Sleep
    3. Does not increase morning Sleepiness
  5. Future Potential uses
    1. Chemotherapeutic

IV. Pathophysiology

  1. Elderly with Insomnia
    1. Low levels of Melatonin
  2. Blind with irregular sleep cycles
    1. Free running Melatonin
    2. Exogenous Melatonin shown to normalize sleep rhythms
      1. Melatonin 5mg at bedtime for 3 weeks
  3. References
    1. Sack (1991) J Biol Rhythms 6:249 [PubMed]

V. Sources

  1. Marketed as a dietary supplement
    1. Not regulated by FDA
    2. No information on production, purity, manufacturer
  2. Risk of impurities
    1. Example: L-Tryptophan related deaths
    2. Consumers should purchase USP Verified products

VI. Dosing

  1. General
    1. Effective doses are lower than package insert
    2. May be effective for promoting sleep onset
    3. Not effective for maintaining sleep (extending sleep duration)
    4. Does not require tapering
  2. Dosing by age
    1. Child: Start at 1 mg (maximum effective dose 3 mg)
    2. Adult: Start at 3 mg (maximum effective dose 6 mg)

VII. Dosing: Specific Indications in Adults

  1. Night Shift Workers
    1. Start with 3 mg prior to daytime sleep (may increase to 5 mg)
  2. Sleep onset Insomnia
    1. Start with 3 mg at 30 to 60 minutes before bedtime (may increase to 5 mg)
  3. Jet Lag
    1. Melatonin 5 mg orally at bedtime on arrival at destination and for 2-6 nights after arrival

VIII. Efficacy: Jet Lag

  1. Recent Cochrane review suggests effective at travel
    1. Indications
      1. Travel across 5 or more time zones
      2. May also be useful if 2 or more time zones crossed
      3. Most effective when traveling eastward
    2. Protocol
      1. Take 5 mg PO at bedtime on arrival at destination
      2. Continue for 2-5 days after arrival
    3. References
      1. Smucny (2002) Am Fam Physician 66(11):2087-8 [PubMed]
  2. Other small trials show benefit at travel time
    1. Petrie (1989) Br Med J 298:705
      1. Before travel: 5 mg PO at bedtime for 3 days
      2. After travel: 5 mg PO at bedtime for 3 days
    2. Petrie (1993) Biol Psychiatry 33:526
      1. After travel: 5 mg PO at bedtime for 5 days
    3. Claustrat (1992) Biol Psychiatry 32:705
      1. Before travel: 8 mg PO at bedtime for 1 day
      2. After travel: 8 mg PO at bedtime for 3 days
  3. Trials showing lack of Melatonin benefit in Jet Lag
    1. Hao (2000) J Clin Endocrinol Metab 85(10):3618-22

IX. Efficacy: Insomnia

  1. Some small trials suggest benefit
    1. Garfinkel (1995) Lancet 346:541
      1. Melatonin 2 mg PO 2 hours before bedtime
    2. Dollins (1994) Proc Natl Acad Sci 91:1824
      1. Melatonin 0.3 to 1 mg PO 1-2 hours before bedtime
    3. Zhadanova (1995) Clin Pharmacol Ther 57:552
      1. Melatonin 0.3 to 1 mg PO 1-2 hours before bedtime

X. Safety

  1. Not recommended in pregnancy and Lactation due to insufficient safety data
  2. May effect growth in children on Melatonin longterm (hormonal suppression)

XI. Adverse Effects: Standard dosing

  1. See Safety as above
  2. Drowsiness
    1. Onset 30 minutes after administered
    2. Duration: 1 hour
  3. Headache
  4. Gastrointestinal upset
  5. Major Depression

XII. Adverse Effects: Higher doses (e.g. 10 mg, often mixed with other supplements)

  1. Hangover Sensation
  2. Lethargy
  3. Disorientation
  4. Amnesia

XIII. Myths: False Claims or myths without scientific support

  1. Anti-Aging effect
  2. Heart and Immune System Strengthening
  3. Improved Sexual Libido and Vitality
  4. Seasonal Affective Disorder treatment

XIV. References

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Related Studies

Ontology: Melatonin (C0025219)

Definition (CHV) a hormone that stimulates color change of the skin and sleep processes in animals
Definition (NCI) A hormone involved in sleep regulatory activity, and a tryptophan-derived neurotransmitter, which inhibits the synthesis and secretion of other neurotransmitters such as dopamine and GABA. Melatonin is synthesized from serotonin intermediate in the pineal gland and the retina where the enzyme 5-hydroxyindole-O-methyltransferase, that catalyzes the last step of synthesis, is found. This hormone binds to and activates melatonin receptors and is involved in regulating the sleep and wake cycles. In addition, melatonin possesses antioxidative and immunoregulatory properties via regulating other neurotransmitters.
Definition (NCI_NCI-GLOSS) A hormone made by the pineal gland (tiny organ near the center of the brain). Melatonin helps control the body's sleep cycle, and is an antioxidant. It is also made in the laboratory and sold as a supplement.
Definition (MSH) A biogenic amine that is found in animals and plants. In mammals, melatonin is produced by the PINEAL GLAND. Its secretion increases in darkness and decreases during exposure to light. Melatonin is implicated in the regulation of SLEEP, mood, and REPRODUCTION. Melatonin is also an effective antioxidant.
Definition (CSP) 5-methoxy-N-acetyltryptamine, a pineal hormone involved in modulation of skin pigmentation, gonad development, and circadian rhythms.
Definition (PDQ) A recombinant therapeutic analog of melatonin, a natural serotonin-derived indole with antioxidant properties. Melatonin hormone synthesis occurs in the pineal gland and depends on beta-adrenergic receptor function. Melatonin is involved in numerous biological functions: circadian rhythm, sleep, stress response, aging, and immunity. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42346&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42346&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C632" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Neuroreactive Substance or Biogenic Amine (T124) , Hormone (T125) , Organic Chemical (T109)
MSH D008550
SnomedCT 116523008, 41199001
LNC LP15036-4, MTHU002350
English Melatonin, melatonin, Acetamide, N-(2-(5-methoxy-1H-indol-3-yl)ethyl)-, MIH, 5-Methoxy-N-acetyltryptamine, N-[2-(5-Methoxy-1H-indol-3-yl)ethyl]acetamide, melanocyte-inhibiting factor, Melatonin [Chemical/Ingredient], MELATONIN, N-[2-(5-methoxyindol-3-yl)ethyl]acetamide, N-Acetyl-5-methoxytryptamine, Melatonin (substance), Melatonin preparation (product), Melatonin preparation, MLT, Melatonin preparation (substance)
Swedish Melatonin
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Spanish preparado de melatonina (producto), melatonina (producto), preparado de melatonina, melatonina (sustancia), melatonina, preparado de melatonina (sustancia), Melatonina
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