Melatonin

1. Indications
   1. Jet Lag
   2. Night Shift Workers with Insomnia
   3. Sleep onset Insomnia
2. Physiology
   1. Pineal gland synthesizes Melatonin from Tryptophan
   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. 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. 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
   6. References
      1. Sack (1991) J Biol Rhythms 6:249 [PubMed]
4. 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
5. 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)
   2. Night Shift Workers
      1. Start with 3 mg prior to daytime sleep (may increase to 5 mg)
   3. Sleep onset Insomnia
      1. Start with 3 mg at 30 to 60 minutes before bedtime (may increase to 5 mg)
   4. Jet Lag
      1. Melatonin 5 mg orally at bedtime on arrival at destination and for 2-6 nights after arrival
6. 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
7. 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
8. Adverse Effects: Standard dosing
   1. Drowsiness
      1. Onset 30 minutes after administered
      2. Duration: 1 hour
   2. Headache
   3. Gastrointestinal upset
   4. Major Depression
9. Adverse Effects: Higher doses
   1. Hangover Sensation
   2. Lethargy
   3. Disorientation
   4. Amnesia
10. 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
11. References
    1. Cupp (1997) Am Fam Physician 56(5):1421-1425 [PubMed]