MELATONIN
MELATONIN
I What it does
Secreted at high levels during the night. Barely detectable during daytime 1
Nighttime secretion may be suppressed by 500 lx of light (bright, not dim, light 13) 1
Bipolar pts are more sensitive to light suppression 2
Not replicated in 2 other studies 3, 4
Sensitivity to light suppression found in young people with bipolar parent, prior to manifestation of sxs 5
Low nocturnal output of melatonin in depressed pts 9, 10, 11, 12.
May be phase shift of melatonin rhythm in depression 13
Bright light in morning advances phase shift, in evening delays nocturnal rise in melatonin 13
As retinal melatonin increases, retinal dopamine decreases 13
Given to mice, prolongs life expectancy by 1/3 21
Promoted to treat insomnia, combat jet lag, prevent pregnancy in large doses, protect cells from free-radicals, boost immune system, prevent cancer, extend life 21
No known LD-50 for animals 21
II. Chemical - what it is
Produced by pineal gland 8
PG is Regulated by adrenergic input 8
Nocturnal secretion of melatonin induced by increased noradrenergic neurotransmission 8
Inhibits gonadal development and function in various mammalian species 8
Seasonal changes in light and dark duration produces variations in melatonin regulation 8
Very short half-life 19
Levels decline steadily into old age 21
III. Melatonin & bright light therapy
Melatonin hypothesis 7
Bright light diminishes secretion of melatonin.
IV. Drug effects/interactions
Atenolol suppresses melatonin secretion, but not effective tx of SADS (6 Rosenthal et al)
Antidepressant tx increases nocturnal melatonin secretion (11, 14, 15, 16)
Propranolol blocks night time melatonin secretion 17
One wk of Desipramine increases melatonin secretion, but after 3 weeks, back to pretreatment levels in healthy subjects, but depressed pts maintain elevated levels. 18
Antipsychotics raise melatonin levels 21 (Newsweek)
Suppresses estrogen, therefore avoid during pregnancy (Sparks lecture on fibromyalgia)
Contraindicated with steroids (Sparks)
V. Insomnia
One study of 12 elderly with controlled release preparation showed effective concentrations through the night 19
No adverse effects
Sleep efficiency improved and time awake after onset of sleep decreased
All had low 6-SMT excretion prior to study.
One study demonstrated that elderly insomniacs have lower peak melatonin levels than noninsomniacs 20
Short-acting 2 mg eliminated in 35-50 minutes
Sustained-release continued to circulate 5-7 hours.
SA improved sleep onset, SR improved maintenance
Insomnia returned upon discontinuation, after 2 months on drug
.
BIBLIOGRAPHY
1. Nurnberger, JI, Goldin, LR, Gershon, ES. (1994). Genetics of Psychiatric Disorders. In Winokur & Clayton (Eds) The Medical Basis of Psychiatry. Saunders: Philadelphia.
2. Lewy et al. (1985). Supersensitivity to light: Possible trait marker for manic-depressive illness. Am J Psychiatry 142:725-727.
3. Comings et al (1991). The dopamine D2 Recepter locus as a modifying gene in neuropsychiatric disorders. JAMA. 266(13): 1793-1800.
4. Whalley et al (1991). Melatonin response to bright light in recovered, drug-free bipolar patients. Psychiatry Res 38:13-19.
5. Nurnberger et al (1988). Supersensitivity to melatonin suppression by light in young people at high risk for affective disorder: A preliminary report. Neuropsychopharmacologty 1:217-223.
6. Rosenthal et al (1988). Atenolol in seasonal affective disorder: a test of the melatonin hypothesis. Am J Psychiatry 145:52-56.
7. Janicak PG et al (1993). Principles and practice of psychopharmacothearpy Williams & Wilkins: Baltimore.
8. Schatzbert, AF et al (1995). Textbook of psychopharmacology. American Psychiatric Press: Washington DC.
9. Boyce, PM (1985). 6-Sulphatoxy melatonin in melancholia. Am J Psychiatry 142:125-127.
10. Nair, PNV & Hariharasubramanian N (1984). Pilapil circadian rhythm of melatonin in endogenous depression. Prog Neuropsychopharmacol Biol Psychiatry 19:1215-1228.
11. Thompson et al (1985). The effect of desipramine upon melatonin and cortisol ssecretion in depressed and normal subjects. British J of Psychiatry 147: 389-393.
12. Thompson et al (1988). A comparion of melatonin secretio in depressed patients and normal subjects British J of psychiatry 147:389-393.
13. Paykel, ES (ed) (1992). Handbook of Affective Disorders. Longman Group: London.
14. Murphy et al (1986). Human plasma melatonin is elevated durihg treatment with monoamine oxidase inhibitors clorgyline and trnylcypromine but not deprenyl. Psychiatry Research 17:119-127.
15. Sack & Lewy (1986). Desmethylimipramine treatment increases melatonin production in humans. Biological Psychiatry 21:406-409.
16. Bearn et al (1988). A study of sulphatoxymelatonin excretion and gonadotrophin status during weight gain in anorexia nervosa. British J of Psychiatry. 152:372-376.
17. Hanssen et al (1977).Effect of propanolol on serum prolactin Lancet 2:309-310.
18. Cowen et al (1985).Plasma melatonin during desmethylimipramine treatment: evidence for changes in noradrenergic transmission. British J of psychiatry 19:799-805.
19. see below
20. see below
21. Newsweek Melatonin. August 7, 1995, Cowley, G
See:
Lewy & Sack (1992). Chronobiologic treatments for circadian phase disorders. Abstracts of the Annual ACNP Meeting, Cecember 1992:8. Using Melatonin for circadian phase disorders.
20. Haimov, I et al (1995) Melatonin replacement therapy of elderly insomniacs. Sleep 18:598-603.
19. Garfinkel D et al (1995). Improvement of sleep quality in elderly people by controlled-release melatonin. Lancet 346:541-4.
Michael Cohen contraceptive effects of high doses
Pierpaoli
Paoli Lissoni - fights lung cancer
Steven Bock “Stay Young the Melatonin Way” claims never a bad reaction, no hang-over.
Ray Sahelian “Melatonin: Nature’s sleeping pill.
James Jan - kids establish normal sleep patterns
University of Iowa Adult Outpatient Psychiatry Department October 30, 1997
(319) 353-6314 After Hours: (319) 356-1616.
MELATONIN
Melatonin may be used to treat insomnia, delayed sleep phase syndrome, fibromyalgia, or jet lag.
Melatonin is a hormone secreted at night by the pineal gland of the brain.
Melatonin is a very short-acting substance, remaining in the body only a few hours.
It is not regulated in this country, so purity and potency of purchased products may vary.
Proper Use of this Medication:
Melatonin is not habit-forming and will not cause a “high” feeling.
Sustained-release preparations tend to work better for maintaining sleep.
Usual dosages are no more than 3 mg at night, taken 1-2 hours before bedtime.
This medication is usually well-tolerated. However, possible side effects may include:
Melatonin may inhibit ovulation, causing some women to have difficulty getting pregnant.
Melatonin may worsen depression.
Headache, “heavy head,” and nausea have been reported, though they tend to be brief.
Side effects associated with long-term use are unknown.
The following other medications may require dosage adjustment while taking melatonin:
Melatonin should not be taken with steroids (cortisone, prednisone, etc.).
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