Dr Thierry HERTOGHE
Abstract
Hertoghe TM, Hertoghe Th, Gadomski A, François M, Everard B, Duboé B
J Eur Anti-Aging Med. 2005; 1: 32-7
A total of 199 human studies (196 different publications) on the relationship between melatonin and sleep, were found through a search on Pubmed, the Internet medical Medline databank: 58 observational and 141 treatment studies. 71% of the observational studies showed a beneficial positive association between the serum or urinary level of melatonin or of one of its metabolites and sleep. 98 of the treatment studies were placebo-controlled studies with 82 (84 %) of them showing significant beneficial results of melatonin supplementation on sleep. Most frequent beneficial effects were a reduction of sleep onset, an efficient muscle relaxation, better resynchronisation of advanced or delayed sleep phase syndromes, and restorations of circadian temperature and sleep-wake cycles. Slow wave sleep and REM stages were rarely significantly improved.
1. Riemann D, Klein T, Rodenbeck A, Feige B, Horny A, Hummel R, Weske G, Al-Shajlawi A, Voderholzer U. Nocturnal cortisol and melatonin secretion in primary insomnia. Psychiatry Res 2002 Dec 15;113(1-2):17-27
2. Rodenbeck A, Huether G, Ruther E, Hajak G. Nocturnal melatonin secretion and its modification by treatment in patients with sleep disorders. Adv Exp Med Biol 1999;467:89-93
3. Hajak G, Rodenbeck A, Staedt J, Bandelow B, Huether G, Ruther E. Nocturnal plasma melatonin levels in patients suffering from chronic primary insomnia. J Pineal Res 1995 Oct;19(3):116-22
4. Blaicher W, Speck E, Imhof MH, Gruber DM, Schneeberger C, Sator MO, Huber JC. Melatonin in postmenopausal females. Arch Gynecol Obstet 2000 Feb;263(3):116-8
5. Leger D, Laudon M, Zisapel N. Nocturnal 6-sulfatoxymelatonin excretion in insomnia and its relation to the response to melatonin replacement therapy. Am J Med. 2004 Jan 15;116(2):91-5. Centre du Sommeil, Hotel-Dieu de Paris, Paris, France.
6. Hansen T, Bratlid T, Lingjarde O, Brenn T. Midwinter insomnia in the subarctic region: evening levels of serum melatonin and cortisol before and after treatment with bright artificial light. Acta Psychiatr Scand 1987 Apr;75(4):428-34
7. Por taluppi F, Cortelli P, Avoni P, Vergnani L, Maltoni P, Pavani A, Sforza E, Degli Uberti EC, Gambetti P, Lugaresi E.Progressive disruption of the circadian rhythm of melatonin in fatal familial insomnia. J Clin Endocrinol Metab 1994 May;78(5):1075-8
8. Benhaberou-Brun D, Lambert C, Dumont M. Association between melatonin secretion and daytime sleep complaints in night nurses. Sleep. 1999 Nov 1;22(7):877-85
9. Leardi S, Tavone E, Cianca G, Barnabei R, Necozione S, Citone G, Simi M.[The role of melatonin in the immediate postoperative period in elderly patients] Minerva Chir 2000 Nov;55(11):745-50
10. Cronin AJ, Keifer JC, Davies MF, King TS, Bixler EO. Melatonin secretion after surgery. : Lancet 2000 Oct 7;356(9237):1244-5
11. Karkela J, Vakkuri O, Kaukinen S, Huang WQ, Pasanen M. The influence of anaesthesia and surgery on the circadian rhythm of melatonin. Acta Anaesthesiol Scand 2002 Jan;46(1):30-6
12. Shilo L, Dagan Y, Smorjik Y, Weinberg U, Dolev S, Komptel B, Balaum H, Shenkman L.Patients in the intensive care unit suffer from severe lack of sleep associated with loss of normal melatonin secretion pattern. A m J Med Sci 1999 May;317(5):278-81
13. Fiorina P, Lattuada G, Silvestrini C, Ponari O, Dall'Aglio P. Disruption of nocturnal melatonin rhythm and immunological involvement in ischaemic stroke patients. Scand J Immunol 1999 Aug;50(2):228-31
14. Luboshitzky R, Shen-Orr Z, Tzischichinsky O, Maldonado M, Herer P, Lavie P. Actigraphic sleep-wake patterns and urinary 6-sulfatoxymelatonin excretion in patients with Alzheimer's disease. Chronobiol Int 2001 May;18(3):513-24
15. Mishima K, Tozawa T, Satoh K, Matsumoto Y, Hishikawa Y, Okawa M. Melatonin secretion rhythm disorders in patients with senile dementia of Alzheimer's type with disturbed sleep-waking. Biol Psychiatry 1999 Feb 15;45(4):417-21
16. Blazejova K, Nevsimalova S, Illnerova H, Hajek I, Sonka K. Sleep disorders and the 24-hour profile of melatonin and cortisol. Sb Lek 2000;101(4):347-51
17. Wikner J, Hirsch U, Wetterberg L, Rojdmark S. Fibromyalgia--a syndrome associated with decreased nocturnal melatonin secretion. Clin Endocrinol (Oxf) 1998 Aug;49(2):179-83
18. Kuhlwein E, Hauger RL, Irwin MR. Abnormal nocturnal melatonin secretion and disordered sleep in abstinent alcoholics. Biol Psychiatry. 2003 Dec 15;54(12):1437-43
19. Shochat T, Luboshitzky R, Lavie P. Nocturnal melatonin onset is phase locked to the primary sleep gate. Am J Physiol 1997 Jul;273(1 Pt 2):R364-70
20. Burgess HJ, Savic N, Sletten T, Roach G, Gilbert SS, Dawson D. The relationship between the dim light melatonin onset and sleep on a regular schedule in young healthy adults. Behav Sleep Med. 2003;1(2):102-14
21. Akerstedt T, Gillberg M, Wetterberg L. The circadian covariation of fatigue and urinary melatonin. Biol Psychiatry 1982 May;17(5):547-54
22. Sadeh A. Sleep and melatonin in infants: a preliminary study. Sleep 1997 Mar;20(3):185-91
23. Morris M, Lack L, Barrett J. The effect of sleep/wake state on nocturnal melatonin excretion. J Pineal Res 1990;9(2):133-8
24. Tzischinsky O, Shlitner A, Lavie P. The association between the nocturnal sleep gate and nocturnal onset of urinary 6-sulfatoxymelatonin. J Biol Rhythms 1993 Fall;8(3):199-209
25. Burgess HJ, Sletten T, Savic N, Gilbert SS, Dawson D. Effects of bright light and melatonin on sleep propensity, temperature, and cardiac activity at night. J Appl Physiol 2001 Sep;91(3):1214-22
26. Lockley SW, Skene DJ, Tabandeh H, Bird AC, Defrance R, Arendt J. Relationship between napping and melatonin in the blind. J Biol Rhythms 1997 Feb;12(1):16-25.
27. Pillar G, Shahar E, Peled N, Ravid S, Lavie P, Etzioni A. Melatonin improves sleep-wake patterns in psychomotor retarded children. Pediatr Neurol 2000 Sep;23(3):225-8
28. Ondze B, Espa F, Ming LC, Chakkar B, Besset A, Billiard M. Advanced sleep phase syndrome. Rev Neurol (Paris) 2001 Nov;157(11 Pt 2):S130-4
29. Lack LC, Mercer JD, Wright H. Circadian rhythms of early morning awakening insomniacs. J Sleep Res 1996 Dec;5(4):211-9
30. Duffy JF, Zeitzer JM, Rimmer DW, Klerman EB, Dijk DJ, Czeisler CA. Peak of circadian melatonin rhythm occurs later within the sleep of older subjects. Am J Physiol Endocrinol Metab 2002 Feb;282(2):E297-303
31. Baskett JJ, Cockrem JF, Todd MA. Melatonin levels in hospitalized elderly patients: a comparison with community based volunteers. Age Ageing 1991 Nov;20(6):430-4
32. Buguet A, Bourdon L, Bisser S, Chapotot F, Radomski MW, Dumas M. Sleeping sickness: major disorders of ircadian rhythm. Med Trop (Mars) 2001;61(4-5):328-39
33. Kripke DF, Elliot JA, Youngstedt SD, Smith JS. Melatonin: marvel or marker? Ann Med 1998 Feb;30(1):81-7
34. Potocki L, Glaze D, Tan DX, Park SS, Kashork CD, Shaffer LG, Reiter RJ, Lupski JR.Circadian rhythm abnormalities of melatonin in Smith-Magenis syndrome. J Med Genet 2000 Jun;37(6):428-33
35. Laakso ML, Leinonen L, Hatonen T, Alila A, Heiskala H. Melatonin, cortisol and body temperature rhythms in Lennox-Gastaut patients with or without circadian rhythm sleep disorders. J Neurol 1993 Jul;240(7):410-6
36. van den Heuvel CJ, Noone JT, Lushington K, Dawson D. Changes in sleepiness and body temperature precede nocturnal sleep onset: evidence from a polysomnographic study in young men. J Sleep Res 1998 Sep;7(3):159-66.
37. Dahl K, Avery DH, Lewy AJ, Savage MV, Brengelmann GL, Larsen LH, Vitiello MV, Prinz PN.Dim light melatonin onset and circadian temperature during a constant routine in hypersomnic winter depression. Acta Psychiatr Scand 1993 Jul;88(1):60-6.
38. Tzischinsky O, Skene D, Epstein R, Lavie P. Circadian rhythms in 6-sulphatoxymelatonin and nocturnal sleep in blind children. Chronobiol Int 1991;8(3):168-75
39. Steindl PE, Finn B, Bendok B, Rothke S, Zee PC, Blei AT. Disruption of the diurnal rhythm of plasma melatonin in cirrhosis. Ann Intern Med 1995 Aug 15;123(4):274-7
40. Steindl PE, Finn B, Bendok B, Rothke S, Zee PC, Blei AT. Changes in the 24-hour rhythm of plasma melatonin in patients with liver cirrhosis--relation to sleep architecture. Wien Klin Wochenschr 1997 Oct 3;109(18):741-6
41. Palm L, Blennow G, Wetterberg L. Long-term melatonin treatment in blind children and young adults with circadian sleep-wake disturbances. Dev Med Child Neurol 1997 May;39(5):319-25
42. Vaughan GM, Allen JP, Tullis W, Siler-Khodr TM, de la Pena A, Sackman JW. Overnight plasma profiles of melatonin and certain adenohypophyseal hormones in men. J Clin Endocrinol Metab 1978 Sep;47(3):566-71
43. Baskett JJ, Wood PC, Broad JB, Duncan JR, English J, Arendt J. Melatonin in older people with age-related sleep maintenance problems: a comparison with age matched normal sleepers. Sleep 2001 Jun 15;24(4):418-24
44. Lushington K, Dawson D, Kennaway DJ, Lack L. The relationship between 6-sulphatoxymelatonin and polysomnographic sleep in good sleeping controls and wake maintenance insomniacs, aged 55-80 years. J Sleep Res 1999 Mar;8(1):57-64
45. Lushington K, Lack L, Kennaway DJ, Rogers N, van den Heuvel C, Dawson D. 6-Sulfatoxymelatonin excretion and self-reported sleep in good sleeping controls and 55-80-year-old insomniacs. J Sleep Res 1998 Jun;7(2):75-83
46. Youngstedt SD, Kripke DF, Elliott JA. Melatonin excretion is not related to sleep in the elderly. J Pineal Res 1998 Apr;24(3):142-5
47. Alvarez B, Dahlitz MJ, Vignau J, Parkes JD. The delayed sleep phase syndrome: clinical and investigative findings in 14 subjects. J Neurol Neurosurg Psychiatry 1992 Aug;55(8):665-70
48. Wikner J, Svanborg E, Wetterberg L, Rojdmark S. Melatonin secretion and excretion in patients with obstructive sleep apnea syndrome. Sleep 1997 Nov;20(11):1002-7
49. Sharp KH, Vaughn GM, Cosby PW, Sewell CE, Kennaway DJ. Alterations of temperature, sleepiness, mood, and performance in residents are not associated with changes in sulfatoxymelatonin excretion. J Pineal Res 1988;5(6):499-512
50. Akerstedt T, Arnetz B, Ficca G, Paulsson LE, Kallner A. A 50-Hz electromagnetic field impairs sleep. J Sleep Res 1999 Mar;8(1):77-81
51. Fletcher A, van den Heuvel C, Dawson D. Sleeping with an electric blanket: effects on core temperature, sleep, and melatonin in young adults. Sleep 1999 May 1;22(3):313-8
52. Press J, Phillip M, Neumann L, Barak R, Segev Y, Abu-Shakra M, Buskila D. Normal melatonin levels in patients with fibromyalgia syndrome. J Rheumatol 1998 Mar;25(3):551-5 ]
53. Claustrat B, Buguet A, Geoffriau M, Bogui P, Mouanga G, Stanghellini A, Dumas M.Plasma melatonin rhythm is maintained in human African trypanosomiasis. Neuroendocrinology 1998 Jul;68(1):64-70
54. Baskett JJ, Broad JB, Wood PC, Duncan JR, Pledger MJ, English J, Arendt J. Does melatonin improve sleep in older people? A randomised crossover trial. Age Ageing. 2003 Mar;32(2):164-70
55. Suzuki S, Dennerstein L, Greenwood KM, Armstrong SM, Sano T, Satohisa E.Melatonin and hormonal changes in disturbed sleep during late pregnancy. J Pineal Res 1993 Nov;15(4):191-8]
56. Brzecka A, Piesiak P, Zareba-Bogdal E, Zierkiewicz G, Plamieniak Z. Rhythm of melatonin excretion in obstructive sleep apnea syndrome. Pneumonol Alergol Pol 2001;69(11-12):650-4
57. Knook L, Kavelaars A, Sinnema G, Kuis W, Heijnen CJ. High nocturnal melatonin in adolescents with chronic fatigue syndrome. J Clin Endocrinol Metab 2000 Oct;85(10):3690-2
58. Gould EL, Loesch DZ, Martin MJ, Hagerman RJ, Armstrong SM, Huggins RM. Melatonin profiles and sleep characteristics in boys with fragile X syndrome: a preliminary study. Am J Med Genet 2000 Dec 11;95(4):307-15
59. Wassmer E, Carter PF, Quinn E, McLean N, Welsh G, Seri S, Whitehouse WP. Melatonin is useful for recording sleep EEGs: a prospective audit of outcome. Dev Med Child Neurol 2001 Nov;43(11):735-8
60. Johnson K, Page A, Williams H, Wassemer E, Whitehouse W The use of melatonin as an alternative to sedation in uncooperative children undergoing an MRI examination. Clin Radiol 2002 Jun;57(6):502-6
61. Schmidt CM, Bohlender JE, Deuster D, Knief A, Matulat P, Dinnesen AG. The use of melatonin as an alternative to sedation in children undergoing brainstem audiometry] Laryngorhinootologie. 2004 Aug;83(8):523-8
62. Smits MG, Nagtegaal EE, van der Heijden J, Coenen AM, Kerkhof GA. Melatonin for chronic sleep onset insomnia in children: a randomised placebo-controlled trial. J Child Neurol 2001 Feb;16(2):86-92
63. Smits MG, van Stel HF, van der Heijden K, Meijer AM, Coenen AM, Kerkhof GA. Melatonin improves health status and sleep in children with idiopathic chronic sleep-onset insomnia: a randomized placebo-controlled trial. J Am Acad Child Adolesc Psychiatry. 2003 Nov;42(11):1286-93.
64. Ivanenko A, Crabtree VM, Tauman R, Gozal D. Melatonin in children and adolescents with insomnia: a retrospective study. Clin Pediatr (Phila). 2003 Jan-Feb;42(1):51-8
65. Jan JE, Hamilton D, Seward N, Fast DK, Freeman RD, Laudon M. Clinical trials of controlled-release melatonin in children with sleep-wake cycle disorders. J Pineal Res 2000 Aug;29(1):34-9
66. Jan JE, Espezel H, Appleton RE. The treatment of sleep disorders with melatonin. Dev Med Child Neurol 1994 Feb;36(2):97-107
67. Dodge NN, Wilson GA .Melatonin for treatment of sleep disorders in children with developmental disabilities. J Child Neurol 2001 Aug;16(8):581-4
68. Zhdanova IV, Wurtman RJ, Wagstaff J. Effects of a low dose of melatonin on sleep in children with Angelman syndrome. J Pediatr Endocrinol Metab 1999 Jan-Feb;12(1):57-67
69. McArthur AJ, Budden SS.Sleep dysfunction in Rett syndrome: a trial of exogenous melatonin treatment. Dev Med Child Neurol 1998 Mar;40(3):186-92 Department of Psychiatry, Oregon Health Sciences University, Portland 97201-3098, USA
70. Jan JE, O'Donnell ME. Use of melatonin in the treatment of paediatric sleep disorders. : J Pineal Res 1996 Nov;21(4):193-9
71. Ramstad K, Loge JH. Melatonin treatment of sleep disorders in disabled children. Tidsskr Nor Laegeforen 2002 Apr 20;122(10):1009-11
27 Pillar G, Shahar E, Peled N, Ravid S, Lavie P, Etzioni A. Melatonin improves sleep-wake patterns in psychomotor retarded children. Pediatr Neurol 2000 Sep;23(3):225-8
72. Jan MM. Melatonin for the treatment of handicapped children with severe sleep disorders. Pediatr Neurol 2000 Sep;23(3):229-32
73. Ross C, Davies P, Whitehouse W. Melatonin treatment for sleep disorders in children with neurodevelopmental disorders: an observational study. Dev Med Child Neurol 2002 May;44(5):339-44
74. Coppola G, Iervolino G, Mastrosimone M, La Torre G, Ruiu F, Pascotto A. Melatonin in wake-sleep disorders in children, adolescents and young adults with mental retardation with or without epilepsy: a double-blind, cross-over, placebo-controlled trial. Brain Dev. 2004 Sep;26(6):373-6
75. Niederhofer H, Staffen W, Mair A, Pittschieler K. Brief report: melatonin facilitates sleep in individuals with mental retardation and insomnia. J Autism Dev Disord. 2003 Aug;33(4):469-72
76. Paavonen EJ, Nieminen-von Wendt T, Vanhala R, Aronen ET, von Wendt L. Effectiveness of melatonin in the treatment of sleep disturbances in children with Asperger disorder. J Child Adolesc Psychopharmacol. 2003 Spring;13(1):83-95
77. Peled N, Shorer Z, Peled E, Pillar G. Melatonin effect on seizures in children with severe neurologic deficit disorders. Epilepsia 2001 Sep;42(9):1208-10
78. 15. Fauteck J, Schmidt H, Lerchl A, Kurlemann G, Wittkowski W. Melatonin in epilepsy: first results of replacement therapy and first clinical results. Biol Signals Recept 1999 Jan-Apr;8(1-2):105-10
79. Ishizaki A, Sugama M, Takeuchi N. Usefulness of melatonin for developmental sleep and emotional/behavior disorders--studies of melatonin trial on 50 patients with developmental disorders. No To Hattatsu 1999 Sep;31(5):428-37
80. Camfield P, Gordon K, Dooley J, Camfield C. Melatonin appears ineffective in children with intellectual deficits and fragmented sleep: six "N of 1" trials.J Child Neurol 1996 Jul;11(4):341-3
81. Zhdanova IV, Raz DJ. Effects of melatonin ingestion on cAMP and cGMP levels in human plasma. J Endocrinol 1999 Dec;163(3):457-62
82. Van Den Heuvel CJ, Kennaway DJ, Dawson D. Effects of daytime melatonin infusion in young adults. Am J Physiol 1998 Jul;275(1 Pt 1):E19-26
83. Lushington K, Pollard K, Lack L, Kennaway DJ, Dawson D. Daytime melatonin administration in elderly good and poor sleepers: effects on core body temperature and sleep latency. Sleep 1997 Dec;20(12):1135-44
84. Mishima K, Satoh K, Shimizu T, Hishikawa Y. Hypnotic and hypothermic action of daytime-administered melatonin. Psychopharmacology (Berl) 1997 Sep;133(2):168-71
85. Krauchi K, Cajochen C, Wirz-Justice A. A relationship between heat loss and sleepiness: effects of postural change and melatonin administration. J Appl Physiol 1997 Jul;83(1):134-9
86. Hughes RJ, Badia P. Sleep-promoting and hypothermic effects of daytime melatonin administration in humans. Sleep 1997 Feb;20(2):124-31
87. Reid K, Van den Heuvel C, Dawson D. Day-time melatonin administration: effects on core temperature and sleep onset latency. J Sleep Res 1996 Sep;5(3):150-4
88. Nave R, Herer P, Haimov I, Shlitner A, Lavie P. Hypnotic and hypothermic effects of melatonin on daytime sleep in humans: lack of antagonism by flumazenil. Neurosci Lett 1996 Aug 23;214(2-3):123-6
89. Cajochen C, Krauchi K, von Arx MA, Mori D, Graw P, Wirz-Justice A. Daytime melatonin administration enhances sleepiness and theta/alpha activity in the waking EEG. Neurosci Lett 1996 Apr 5;207(3):209-13
90. Dijk DJ, Roth C, Landolt HP, Werth E, Aeppli M, Achermann P, Borbely AA. Melatonin effect on daytime sleep in men: suppression of EEG low frequency activity and enhancement of spindle frequency activity. Neurosci Lett 1995 Dec 1;201(1):13-6
91. Deacon S, Arendt J. Melatonin-induced temperature suppression and its acute phase-shifting effects correlate in a dose-dependent manner in humans. Brain Res 1995 Aug 7;688(1-2):77-85
92. Satomura T, Sakamoto T, Shirakawa S, Tsutsumi Y, Mukai M, Ohyama T, Uchimura N, Maeda H. Hypnotic action of melatonin during daytime administration and its comparison with triazolam. Psychiatry Clin Neurosci 2001 Jun;55(3):303-4
93. Nave R, Iani C, Herer P, Gopher D, Lavie P. Residual effects of daytime administration of melatonin on performance relevant to flight. Behav Brain Res 2002 Apr 1;131(1-2):87-95 Sleep Research Laboratory, Faculty of Medicine, Technion-Israel Institute of Technology, Gutwirth Building, 32000, Haifa, Israel.
94. Matsumoto M. The hypnotic effects of melatonin treatment on diurnal sleep in humans. Psychiatry Clin Neurosci 1999 Apr;53(2):243-5
95. Gilbert SS, van den Heuvel CJ, Dawson D. Daytime melatonin and temazepam in young adult humans: equivalent effects on sleep latency and body temperatures. J Physiol 1999 Feb 1;514 ( Pt 3):905-14
96. Rogers NL, Kennaway DJ, Dawson D. Neurobehavioural performance effects of daytime melatonin and temazepam administration. J Sleep Res. 2003 Sep;12(3):207-12
97. Deacon S, English J, Arendt J. Acute phase-shifting effects of melatonin associated with suppression of core body temperature in humans. Neurosci Lett 1994 Aug 29;178(1):32-4
98. Dollins AB, Zhdanova IV, Wurtman RJ, Lynch HJ, Deng MH. Effect of inducing nocturnal serum melatonin concentrations in daytime on sleep, mood, body temperature, and performance. Proc Natl Acad Sci U S A 1994 Mar 1;91(5):1824-8
99. Dollins AB, Lynch HJ, Wurtman RJ, Deng MH, Kischka KU, Gleason RE, Lieberman HR.Effect of pharmacological daytime doses of melatonin on human mood and performance. Psychopharmacology (Berl) 1993;112(4):490-6
100. Arendt J, Borbely AA, Franey C, Wright J. The effects of chronic, small doses of melatonin given in the late afternoon on fatigue in man: a preliminary study. Neurosci Lett 1984 Apr 6;45(3):317-21
101. Wright J, Aldhous M, Franey C, English J, Arendt J. The effects of exogenous melatonin on endocrine function in man. Clin Endocrinol (Oxf) 1986 Apr;24(4):375-82
102. Lieberman HR, Waldhauser F, Garfield G, Lynch HJ, Wurtman RJ. Effects of melatonin on human mood and performance. Brain Res 1984 Dec 10;323(2):201-7
103. Cramer H, Bohme W, Kendel K, Donnadieu M. Liberation of growth hormone and melanocyte-stimulating hormone in natural and melatonin-induced human sleep. Arzneimittelforschung 1976;26(6):1076-8
104. Harris AS, Burgess HJ, Dawson D. The effects of day-time exogenous melatonin administration on cardiac autonomic activity. J Pineal Res 2001 Oct;31(3):199-205
105. Rajaratnam SM, Middleton B, Stone BM, Arendt J, Dijk DJ. Melatonin advances the circadian timing of EEG sleep and directly facilitates sleep without altering its duration in extended sleep opportunities in humans. J Physiol. 2004 Nov 15;561(Pt 1):339-51
106. Holmes AL, Gilbert SS, Dawson D. Melatonin and zopiclone: the relationship between sleep propensity and body temperature. Sleep 2002 May 1;25(3):301-6
107. Paul MA, Gray G, Kenny G, Pigeau RA. Impact of melatonin, zaleplon, zopiclone, and temazepam on psychomotor performance. Aviat Space Environ Med. 2003 Dec;74(12):1263-70
108. Paul MA, Gray G, MacLellan M, Pigeau RA. Sleep-inducing pharmaceuticals: a comparison of melatonin, zaleplon, zopiclone, and temazepam. Aviat Space Environ Med. 2004 Jun;75(6):512-9
109. Wesensten NJ, Balkin TJ, Reichardt RM, Kautz MA, Saviolakis GA, Belenky G. Daytime sleep and performance following a zolpidem and melatonin cocktail. Sleep. 2005 Jan 1;28(1):93-103
110. Rajaratnam SM, Dijk DJ, Middleton B, Stone BM, Arendt J. Melatonin phase-shifts human circadian rhythms with no evidence of changes in the duration of endogenous melatonin secretion or the 24-hour production of reproductive hormones. J Clin Endocrinol Metab. 2003 Sep;88(9):4303-9.
111. Nickelsen T, Demisch L, Demisch K, Radermacher B, Schoffling K. Influence of subchronic intake of melatonin at various times of the day on fatigue and hormonal levels: a placebo-controlled, double-blind trial. J Pineal Res 1989;6(4):325-34
112. Tzischinsky O, Lavie P. Melatonin possesses time-dependent hypnotic effects. Sleep 1994 Oct;17(7):638-45
113. Nave R, Peled R, Lavie P. Melatonin improves evening napping. Eur J Pharmacol 1995 Mar 6;275(2):213-6
114. Stone BM, Turner C, Mills SL, Nicholson AN. Hypnotic activity of melatonin. Sleep 2000 Aug 1;23(5):663-
115. Zhdanova IV, Wurtman RJ, Lynch HJ, Ives JR, Dollins AB, Morabito C, Matheson JK, Schomer DL.Sleep-inducing effects of low doses of melatonin ingested in the evening. Clin Pharmacol Ther 1995 May;57(5):552-8
116. Zhdanova IV, Wurtman RJ, Morabito C, Piotrovska VR, Lynch HJ. Effects of low oral doses of melatonin, given 2-4 hours before habitual bedtime, on sleep in normal young humans. Sleep 1996 Jun;19(5):423-31
117. Waldhauser F, Saletu B, Trinchard-Lugan I. Sleep laboratory investigations on hypnotic properties of melatonin. Psychopharmacology (Berl) 1990;100(2):222-6
118. Seabra ML, Bignotto M, Pinto LR Jr, Tufik S. Randomized, double-blind clinical trial, controlled with placebo, of the toxicology of chronic melatonin treatment. J Pineal Res 2000 Nov;29(4):193-200
119. Pires ML, Benedito-Silva AA, Pinto L, Souza L, Vismari L, Calil HM. Acute effects of low doses of melatonin on the sleep of young healthy subjects. J Pineal Res 2001 Nov;31(4):326-32
120. Shirakawa SI, Sakamoto T, Uchimura N, Tsutsumi Y, Tanaka J, Maeda H. Effect of melatonin on sleep and rectal temperature of young healthy evening types. Psychiatry Clin Neurosci 2001 Jun;55(3):301-2
121. Pinto LR Jr, Seabra Mde L, Tufik S. Different criteria of sleep latency and the effect of melatonin on sleep consolidation. Sleep. 2004 Sep 15;27(6):1089-92
122. Ferini-Strambi L, Zucconi M, Biella G, Stankov B, Fraschini F, Oldani A, Smirne S. Effect of melatonin on sleep microstructure: preliminary results in healthy subjects. Sleep 1993 Dec;16(8):744-7
123. Attenburrow ME, Cowen PJ, Sharpley AL. Low dose melatonin improves sleep in healthy middle-aged subjects. Psychopharmacology (Berl) 1996 Jul;126(2):179-81
124. Garfinkel D, Laudon M, Nof D, Zisapel N. Improvement of sleep quality in elderly people by controlled-release melatonin. Lancet 1995 Aug 26;346(8974):541-4 Day Care Unit, E Wolfson Medical Center, Holon, Israel. Comment in: Lancet. 1995 Dec 2;346(8988):1491.
125. Garfinkel D, Laudon M, Zisapel N. Improvement of sleep quality by controlled-release melatonin in benzodiazepine-treated elderly insomniacs. Arch Gerontol Geriatr. 1997 Mar-Apr;24(2):223-31
126. Monti JM, Alvarino F, Cardinali D, Savio I, Pintos A. Polysomnographic study of the effect of melatonin on sleep in elderly patients with chronic primary insomnia. Arch Gerontol Geriatr. 1999 Mar-Apr;28(2):85-98
127. Pawlikowski M, Kolomecka M, Wojtczak A, Karasek M. Effects of six months melatonin treatment on sleep quality and serum concentrations of estradiol, cortisol, dehydroepiandrosterone sulfate, and somatomedin C in elderly women. Neuroendocrinol Lett 2002 Apr;23 Suppl 1:17-9
128. Siegrist C, Benedetti C, Orlando A, Beltran JM, Tuchscherr L, Noseda CM, Brusco LI, Cardinali DP.Lack of changes in serum prolactin, FSH, TSH, and estradiol after melatonin treatment in doses that improve sleep and reduce benzodiazepine consumption in sleep-disturbed, middle-aged, and elderly patients. J Pineal Res 2001 Jan;30(1):34-42
129. Jean-Louis G, von Gizycki H, Zizi F. Melatonin effects on sleep, mood, and cognition in elderly with mild cognitive impairment. J Pineal Res 1998 Oct;25(3):177-83
130. Haimov I, Lavie P, Laudon M, Herer P, Vigder C, Zisapel N. Melatonin replacement therapy of elderly insomniacs. Sleep 1995 Sep;18(7):598-603
131. Zhdanova IV, Wurtman RJ, Regan MM, Taylor JA, Shi JP, Leclair OU. Melatonin treatment for age-related insomnia. J Clin Endocrinol Metab 2001 Oct;86(10):4727-30
132. Hughes RJ, Sack RL, Lewy AJ. The role of melatonin and circadian phase in age-related sleep-maintenance insomnia: assessment in a clinical trial of melatonin replacement. Sleep 1998;21(1):52-68
133. Jean-Louis G, von Gizycki H, Zizi F. Melatonin effects on sleep, mood, and cognition in elderly with mild cognitive impairment. J Pineal Res 1998 Oct;25(3):177-83
134. MacFarlane JG, Cleghorn JM, Brown GM, Streiner DL. The effects of exogenous melatonin on the total sleep time and daytime alertness of chronic insomniacs: a preliminary study. Biol Psychiatry 1991 Aug 15;30(4):371-6
135. Andrade C, Srihari BS, Reddy KP, Chandramma L. Melatonin in medically ill patients with insomnia: a double-blind, placebo-controlled study. J Clin Psychiatry 2001 Jan;62(1):41-5
136. Garfinkel D, Zisapel N, Wainstein J, Laudon M. Facilitation of benzodiazepine discontinuation by melatonin: a new clinical approach. Arch Intern Med 1999 Nov 8;159(20):2456-60
137. Dahlitz M, Alvarez B, Vignau J, English J, Arendt J, Parkes JD. Delayed sleep phase syndrome response to melatonin. Lancet 1991 May 11;337(8750):1121-4
138. Dagan Y, Yovel I, Hallis D, Eisenstein M, Raichik I. Evaluating the role of melatonin in the long-term treatment of delayed sleep phase syndrome (DSPS). Chronobiol Int 1998 Mar;15(2):181-90
139. Kayumov L, Brown G, Jindal R, Buttoo K, Shapiro CM. A randomized, double-blind, placebo-controlled crossover study of the effect of exogenous melatonin on delayed sleep phase syndrome. Psychosom Med 2001 Jan-Feb;63(1):40-8
140. Okawa M, Uchiyama M, Ozaki S, Shibui K, Kamei Y, Hayakawa T, Urata J. Melatonin treatment for circadian rhythm sleep disorders. Psychiatry Clin Neurosci 1998 Apr;52(2):259-60
141. Kamei Y, Hayakawa T, Urata J, Uchiyama M, Shibui K, Kim K, Kudo Y, Okawa M. Melatonin treatment for circadian rhythm sleep disorders. Psychiatry Clin Neurosci 2000 Jun;54(3):381-2
142. Nagtegaal JE, Kerkhof GA, Smits MG, Swart AC, Van Der Meer YG. Delayed sleep phase syndrome: A placebo-controlled cross-over study on the effects of melatonin administered five hours before the individual dim light melatonin onset. J Sleep Res 1998 Jun;7(2):135-43
143. Oldani A, Ferini-Strambi L, Zucconi M, Stankov B, Fraschini F, Smirne S. Melatonin and delayed sleep phase syndrome: ambulatory polygraphic evaluation. Neuroreport 1994 Dec 30;6(1):132-4
144. Kunz D, Mahlberg R, Muller C, Tilmann A, Bes F. Melatonin in patients with reduced REM sleep duration: two randomized controlled trials. J Clin Endocrinol Metab. 2004 Jan;89(1):128-34
145. Takeuchi N, Uchimura N, Hashizume Y, Mukai M, Etoh Y, Yamamoto K, Kotorii T, Ohshima H, Ohshima M, Maeda H. Melatonin therapy for REM sleep behavior disorder. Psychiatry Clin Neurosci 2001 Jun;55(3):267-9
146. Kunz D, Bes F. Melatonin as a therapy in REM sleep behavior disorder patients: an open-labeled pilot study on the possible influence of melatonin on REM-sleep regulation. Mov Disord 1999 May;14(3):507-11
147. Boeve BF, Silber MH, Ferman TJ. Melatonin for treatment of REM sleep behavior disorder in neurologic disorders: results in 14 patients. Sleep Med. 2003 Jul;4(4):281-4
148. Suhner A, Schlagenhauf P, Johnson R, Tschopp A, Steffen R. Comparative study to determine the optimal melatonin dosage form for the alleviation of jet lag. Chronobiol Int 1998 Nov;15(6):655-66
149. Petrie K, Dawson AG, Thompson L, Brook R. A double-blind trial of melatonin as a treatment for jet lag in international cabin crew. Biol Psychiatry 1993 Apr 1;33(7):526-30
150. Paul MA, Gray G, Sardana TM, Pigeau RA. Melatonin and zopiclone as facilitators of early circadian sleep in operational air transport crews. Aviat Space Environ Med. 2004 May;75(5):439-43
151. Jorgensen KM, Witting MD. Does exogenous melatonin improve day sleep or night alertness in emergency physicians working night shifts? Ann Emerg Med 1998 Jun;31(6):699-704
152. Dawson D, Encel N, Lushington K. Improving adaptation to simulated night shift: timed exposure to bright light versus daytime melatonin administration. Sleep 1995 Jan;18(1):11-21
153. Folkard S, Arendt J, Clark M. Can melatonin improve shift workers' tolerance of the night shift? Some preliminary findings. Chronobiol Int 1993 Oct;10(5):315-20
154. Sharkey KM, Fogg LF, Eastman CI. Effects of melatonin administration on daytime sleep after simulated night shift work. J Sleep Res 2001 Sep;10(3):181-92
155. Yoon IY, Song BG. Role of morning melatonin administration and attenuation of sunlight exposure in improving adaptation of night-shift workers. Chronobiol Int 2002 Sep;19(5):903-13
156. Yang CM, Spielman AJ, D'Ambrosio P, Serizawa S, Nunes J, Birnbaum J. A single dose of melatonin prevents the phase delay associated with a delayed weekend sleep pattern. Sleep 2001 May 1;24(3):272-81
157. Middleton B, Arendt J, Stone BM. Complex effects of melatonin on human circadian rhythms in constant dim light. J Biol Rhythms 1997 Oct;12(5):467-77
158. Milstein V, Small JG, Spencer DW. Melatonin for sleep EEG. Clin Electroencephalogr 1998 Jan;29(1):49-53
159. Naguib M, Samarkandi AH. Premedication with melatonin: a double-blind, placebo-controlled comparison with midazolam. Br J Anaesth 1999 Jun;82(6):875-80
160. Acil M, Basgul E, Celiker V, Karagoz AH, Demir B, Aypar U. Perioperative effects of melatonin and midazolam premedication on sedation, orientation, anxiety scores and psychomotor performance. Eur J Anaesthesiol. 2004 Jul;21(7):553-7
161. Dalton EJ, Rotondi D, Levitan RD, Kennedy SH, Brown GM. Use of slow-release melatonin in treatment-resistant depression. J Psychiatry Neurosci 2000 Jan;25(1):48-52
162. Dolberg OT, Hirschmann S, Grunhaus L. Melatonin for the treatment of sleep disturbances in major depressive disorder. Am J Psychiatry 1998 Aug;155(8):1119-21
163. Wirz-Justice A, Graw P, Krauchi K, Gisin B, Arendt J, Aldhous M, Poldinger W. Morning or night-time melatonin is ineffective in seasonal affective disorder. J Psychiatr Res 1990;24(2):129-37
164. Leppamaki S, Partonen T, Vakkuri O, Lonnqvist J, Partinen M, Laudon M. Effect of controlled-release melatonin on sleep quality, mood, and quality of life in subjects with seasonal or weather-associated changes in mood and behaviour. Eur Neuropsychopharmacol. 2003 May;13(3):137-45
165. Bersani G, Garavini A. Melatonin add-on in manic patients with treatment resistant insomnia. Prog Neuropsychopharmacol Biol Psychiatry 2000 Feb;24(2):185-91
166. Shamir E, Laudon M, Barak Y, Anis Y, Rotenberg V, Elizur A, Zisapel N. Melatonin improves sleep quality of patients with chronic schizophrenia. J Clin Psychiatry 2000 May;61(5):373-7
167. Brusco LI, Fainstein I, Marquez M, Cardinali DP. Effect of melatonin in selected populations of sleep-disturbed patients. Biol Signals Recept 1999 Jan-Apr;8(1-2):126-31
168. Asayama K, Yamadera H, Ito T, Suzuki H, Kudo Y, Endo S. Double blind study of melatonin effects on the sleep-wake rhythm, cognitive and non-cognitive functions in Alzheimer type dementia. J Nippon Med Sch. 2003 Aug;70(4):334-41
169. Domzal TM, Kaca-Orynska M, Zaleski P. Melatonin in sleep rhythm disorders after cerebral stroke. Pol Merkuriusz Lek 2000 Jun;8(48):411-2
170. O'Callaghan FJ, Clarke AA, Hancock E, Hunt A, Osborne JP.Use of melatonin to treat sleep disorders in tuberous sclerosis. Dev Med Child Neurol 1999 Feb;41(2):123-6
171. Rosenberg SI, Silverstein H, Rowan PT, Olds MJ. Effect of melatonin on tinnitus. Laryngoscope 1998 Mar;108(3):305-10
172. Sack RL, Brandes RW, Kendall AR, Lewy AJ. Entrainment of free-running circadian rhythms by melatonin in blind people. N Engl J Med 2000 Oct 12;343(15):1070-7
173. Sack RL, Lewy AJ, Blood ML, Stevenson J, Keith LD. Melatonin administration to blind people: phase advances and entrainment. J Biol Rhythms 1991 Fall;6(3):249-61
174. Fischer S, Smolnik R, Herms M, Born J, Fehm HL. Melatonin acutely improves the neuroendocrine architecture of sleep in blind individuals. J Clin Endocrinol Metab. 2003 Nov;88(11):5315-20
175. Hack LM, Lockley SW, Arendt J, Skene DJ. The effects of low-dose 0.5-mg melatonin on the free-running circadian rhythms of blind subjects. J Biol Rhythms. 2003 Oct;18(5):420-9
176. Citera G, Arias MA, Maldonado-Cocco JA, Lazaro MA, Rosemffet MG, Brusco LI, Scheines EJ, Cardinalli DP.The effect of melatonin in patients with fibromyalgia: a pilot study. Clin Rheumatol 2000;19(1):9-13
177. Scheer FA, Van Montfrans GA, van Someren EJ, Mairuhu G, Buijs RM. Daily nighttime melatonin reduces blood pressure in male patients with essential hypertension. Hypertension. 2004 Feb;43(2):192-7
178. Campos FL, da Silva-Junior FP, de Bruin VM, de Bruin PF. Melatonin improves sleep in asthma: a randomized, double-blind, placebo-controlled study. Am J Respir Crit Care Med. 2004 Nov 1;170(9):947-51
179. Shilo L, Dagan Y, Smorjik Y, Weinberg U, Dolev S, Komptel B, Shenkman L. Effect of melatonin on sleep quality of COPD intensive care patients: a pilot study. Chronobiol Int 2000 Jan;17(1):71-6
180. van den Heuvel CJ, Kennaway DJ, Dawson D. Thermoregulatory and soporific effects of very low dose melatonin injection. Am J Physiol 1999 Feb;276(2 Pt 1):E249-54
181. Atkinson G, Buckley P, Edwards B, Reilly T, Waterhouse J. Are there hangover-effects on physical performance when melatonin is ingested by athletes before nocturnal sleep? Int J Sports Med 2001 Apr;22(3):232-4
182. James SP, Mendelson WB, Sack DA, Rosenthal NE, Wehr TA. The effect of melatonin on normal sleep. Neuropsychopharmacology 1987 Dec;1(1):41-4
183. Dawson D, Rogers NL, van den Heuvel CJ, Kennaway DJ, Lushington K. Effect of sustained nocturnal transbuccal melatonin administration on sleep and temperature in elderly insomniacs. J Biol Rhythms 1998 Dec;13(6):532-8
184. Ellis CM, Lemmens G, Parkes JD. Melatonin and insomnia. J Sleep Res 1996 Mar;5(1):61-5
185. Almeida Montes LG, Ontiveros Uribe MP, Cortes Sotres J, Heinze Martin G. Treatment of primary insomnia with melatonin: a double-blind, placebo-controlled, crossover study. J Psychiatry Neurosci. 2003 May;28(3):191-6
186. Spitzer RL, Terman M, Williams JB, Terman JS, Malt UF, Singer F, Lewy AJ. Jet lag: clinical features, validation of a new syndrome-specific scale, and lack of response to melatonin in a randomized, double-blind trial. Am J Psychiatry 1999 Sep;156(9):1392-6
187. Edwards BJ, Atkinson G, Waterhouse J, Reilly T, Godfrey R, Budgett R. Use of melatonin in recovery from jet-lag following an eastward flight across 10 time-zones. : Ergonomics 2000 Oct;43(10):1501-13
188. Jockovich M, Cosentino D, Cosentino L, Wears RL, Seaberg DC. Effect of exogenous melatonin on mood and sleep efficiency in emergency medicine residents working night shifts. Acad Emerg Med 2000 Aug;7(8):955-8
189. Wright SW, Lawrence LM, Wrenn KD, Haynes ML, Welch LW, Schlack HM. Randomized clinical trial of melatonin after night-shift work: efficacy and neuropsychologic effects. Ann Emerg Med 1998 Sep;32(3 Pt 1):334-40
190. James M, Tremea MO, Jones JS, Krohmer JR. Can melatonin improve adaptation to night shift? Am J Emerg Med 1998 Jul;16(4):367-70
191. Leibenluft E, Feldman-Naim S, Turner EH, Wehr TA, Rosenthal NE. Effects of exogenous melatonin administration and withdrawal in five patients with rapid-cycling bipolar disorder. J Clin Psychiatry 1997 Sep;58(9):383-8
192. Singer C, Tractenberg RE, Kaye J, Schafer K, Gamst A, Grundman M, Thomas R, Thal LJ; Alzheimer's Disease Cooperative Study. A multicenter, placebo-controlled trial of melatonin for sleep disturbance in Alzheimer's disease. Sleep. 2003 Nov 1;26(7):893-901
193. Serfaty M, Kennell-Webb S, Warner J, Blizard R, Raven P.D ouble blind randomised placebo controlled trial of low dose melatonin for sleep disorders in dementia. Int J Geriatr Psychiatry 2002 Dec;17(12):1120-7
194. Cohen-Mansfield J, Garfinkel D, Lipson S. Melatonin for treatment of sundowning in elderly persons with dementia – a preliminary study. Arch Gerontol Geriatr 2000 Aug 1;31(1):65-76
195. Kemp S, Biswas R, Neumann V, Coughlan A. The value of melatonin for sleep disorders occurring post-head injury: a pilot RCT. Brain Inj. 2004 Sep;18(9):911-9
196. Cardinali DP, Gvozdenovich E, Kaplan MR, Fainstein I, Shifis HA, Perez Lloret S, Albornoz L, Negri A.A double blind-placebo controlled study on melatonin efficacy to reduce anxiolytic benzodiazepine use in the elderly. Neuroendocrinol Lett 2002 Feb;23(1):55-60