1. Ustun T, Privett M, Lecrubier Y, et al. Form, frequency and burden
of sleep problems in general health care: a report from the WHO
collaborative study on psychological problems in general health
care. Eur Psychiatry. 1996;11:1087-1096.
2. Ancoli-Israel S, Roth T. Characteristics of insomnia in the United
States: results of the 1991 national sleep foundation survey. I. Sleep.
1999;22(suppl):S347-S353.
3. Walsh J, Ustan Bedirhan T. Prevalence and health consequences of
insomnia. Sleep. 1999;22:427-436.
4. Zammit KG, Weiner J, Damato N, et al. Quality of life in people
with insomnia. Sleep. 1999;22(suppl):S379-S385.
5. Leger D, Guilleminault C, Dreyfus JP, et al. Prevalence of insomnia
in a survey of 12,778 adults in France. J Sleep Res. 2000;9:35-42.
6. Leger D, Scheuermaier K, Philip P, et al. SF-36: evaluation of quality
of life in severe and mild insomniacs compared with good sleepers.
Psychosom Med. 2001;63:49-55.
7. Carskadon MA, Dement WC, Mitler MM, et al. Self-reports versus
sleep laboratory findings in 122 drug-free subjects with complaints
of chronic insomnia. Am J Psychiatry. 1976;133:1382-1388.
8. McCall WV, Edinger JD. Subjective total insomnia: an example of
sleep state misperception. Sleep. 1992;15:71-73.
9. Laudon M, Zisapel N. Melatonin deficiency and its implications for
the treatment of insomnia in elderly subjects. Aging Male. 1998;1:
1-8.
10. Bojkowski CJ, Aldhous M, English J, et al. Suppression of nocturnal
plasma melatonin and 6-sulphatoxymelatonin by bright and dim
light in man. Horm Metab Res. 1987;19:437-440.
11. Sharma M, Palacios-Bois J, Schwartz G, et al. Circadian rhythms of
melatonin and cortisol in aging. Biol Psychiatry. 1989;25:305-319.
12. Nair NPV, Hariharasubramanian N, Pilapil C, et al. Plasma melatonin
-an index of brain aging in humans? Biol Psychiatry. 1986;
21:141-150.
13. Waldhauser F, Weiszenbacher G, Tatzer E, et al. Alternations in
nocturnal serum melatonin levels in humans with growth and aging.
J Clin Endocrinol Metab. 1988;66:648-652.
14. van Coevorden A, Mockel J, Laurent E, et al. Neuroendocrine
rhythms and sleep in aging men. Am J Physiol. 1991;260:E651-
E661.
15. Kennaway DJ, Lushington K, Dawson D, et al. Urinary 6-sulfatoxymelatonin
excretion and aging: new results and a critical review
of the literature. J Pineal Res. 1999;27:210-220.
16. Haimov I, Laudon M, Zisapel N, et al. Sleep disorders and melatonin
rhythms in elderly people. BMJ. 1994;309:167.
17. Zeitzer JM, Daniels JE, Duffy JF, et al. Do plasma melatonin concentrations
decline with age? Am J Med. 1999;107:432-436.
18. Czeisler CA, Dumont M, Duffy JF, et al. Association of sleep-wake
habits in older people with changes in output of circadian pacemaker.
Lancet. 1992;340:933-936.
19. MacFarlane J, Cleghorn J, Brown G. Melatonin and core temperature
rhythm in chronic insomnia. Adv Biosci. 1984;53:303-306.
20. 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.
21. Hajak G, Rodenbeck A, Adler L, et al. Nocturnal melatonin secretion
and sleep after doxepin administration in chronic primary insomnia.
Pharmacopsychiatry. 1996;29:187-192.
94 January 15, 2004 THE AMERICAN JOURNAL OF MEDICINE_ Volume 116
22. Lushington K, Lack L, Kennaway DJ, et al. 6-Sulfatoxymelatonin
excretion and self-reported sleep in good sleeping controls and 55-
80-year-old insomniacs. J Sleep Res. 1998;7:75-83.
23. 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;8:57-64.
24. Malik FS, Mehra MR, Ali A, et al. Nocturnal melatonin release
impairment and clinical effects of exogenous melatonin in chronic
heart failure. J Am Coll Cardiol. 1997;29(suppl A):370A.
25. Petterborg LJ, Thalen BE, Kjellman BF, Wetterberg L. Effect of melatonin
replacement on serum hormone rhythms in a patient lacking
endogenous melatonin. Brain Res Bull. 1991;27:181-185.
26. Garfinkel D, Laudon M, Nof D, Zisapel N. Improvement of sleep
quality in elderly people by controlled-release melatonin. Lancet.
1995;346:541-544.
27. Haimov I, Lavie P, Laudon M, et al. Melatonin replacement therapy
of elderly insomniacs. Sleep. 1995;18:598-603.
28. Wurtman RJ, Zhdanova I. Improvement of sleep quality by melatonin.
Lancet. 1995;346:1491.
29. van den Heuvel C, Reid K, Dawson D. Effect of atenolol on nocturnal
sleep and temperature in young men: reversal by pharmacological
doses of melatonin. Psychol Behav. 1997;61:795-802.
30. Hughes RJ, Sack R, Lewy A. The role of melatonin and circadian
phase in age-related sleep-maintenance insomnia: assessment in a
clinical trial of melatonin replacement. Sleep. 1998;21:52-68.
31. Kripke D, Elliot J, Youngstedt S, Smith J. Melatonin: marvel or
marker? Ann Med. 1998;30:81-87.
32. Youngstedt SD, Kripke DF, Elliott JA. Melatonin excretion is not
related to sleep in the elderly. J Pineal Res. 1998;24:142-145.
33. Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition
(DSM-IV). Washington, DC: American Psychiatric Association;
1994.
34. Lipman RS. Differentiating anxiety and depression in anxiety
disorders: use of rating scales. Psychopharmacol Bull. 1982;18:69-
77.
35. Raskin H, Schulterbrandt J, Reatig N, McKeon JJ. Replication of
factors of psychopathology in interview, ward behaviour and selfreport
ratings of hospitalised depressives. J Nerv Ment Dis. 1969;
148:87-98.
36. Kukull WA, Larson EB, Teri L, et al. The Mini-Mental State Examination
score and the clinical diagnosis of dementia. J Clin Epidemiol.
1994;47:1061-1067.
37. Luboshitzky R, Shen-Orr Z, Tzischichinsky O, et al. Actigraphic
sleep-wake patterns and urinary 6-sulfatoxymelatonin excretion in
patients with Alzheimer's disease. Chronobiol Int. 2001;18:513-524.
38. Cugini P, Touitou Y, Bogdan A, et al. Is melatonin circadian
rhythm a physiological feature associated with healthy longevity? A
study of long-living subjects and their progeny. Chronobiol Int.
2001;18:99-107.
39. Baskett JJ, Wood PC, Broad JB, et al. Melatonin in older people with
age-related sleep maintenance problems: a comparison with age
matched normal sleepers. Sleep. 2001;24:418-424.
40. Duffy JF, Zeitzer JM, Rimmer DW, et al. Peak of circadian melatonin
rhythm occurs later within the sleep of older subjects. Am J
Physiol Endocrinol Metab. 2002;282:E297-E303.
41. Arendt J, Bojkowski C, Franey C, et al. Immunoassay of 6-hydroxymelatonin
sulfate in human plasma and urine: abolition of
the urinary 24-hour rhythm with atenolol. J Clin Endocrinol Metab.
1985;60:1166-1173.
42. Zisapel N, Laudon M. Subjective assessment of the effects of CNSactive
drugs on sleep by the Leeds sleep evaluation questionnaire: a
review. Hum Psychopharmacol. 2003;18:1-20.
43. Graw P, Haug HJ, Leonhardt G, Wirz-Justice A. Sleep deprivation
response in seasonal affective disorder during a 40-h constant routine.
J Affect Disord. 1998;48:69-74.
44. Haug H, Fahndrich E. Problems in defining response in therapy
studies. Pharmacopsychiatry. 1986;19:1710-1711.
45. Powell CV, Kelly AM, Williams A. Determining the minimum clinically
significant difference in visual analog pain score for children.
Ann Emerg Med. 2001;37:28-31.
46. Brugger P, Markti W, Herold M. Impaired nocturnal secretion of
melatonin in coronary heart disease. Lancet. 1995;345:1408.
47. Sakotnik A, Liebmann PM, Stoschitzky K, et al. Decreased melatonin
synthesis in patients with coronary artery disease. Eur Heart J.
1999;20:1314-1317.
48. Girotti L, Lago M, Ianovsky O, et al. Low urinary 6-sulphatoxymelatonin
levels in patients with coronary artery disease. J Pineal
Res. 2000;29:138-142.
49. Wetterberg L, Bergiannaki JD, Paparrigopoulos T, et al. Normative
melatonin excretion: a multinational study. Psychoneuroendocrinology.
1999;24:209-226.
Nocturnal 6-Sulfatoxymelatonin Excretion in Insomnia/Leger et al
Publicado el 27 de abril de 2004
Terapia sustitutiva
Insomnio y respuesta a la terapia con melatonina
Existiría una asociación entre los disturbios relacionados con la edad en el ciclo sueño-vigilia, y la declinación en la producción de melatonina.
Autor/a: Dres. Leger D, Laudon M, Zisapel N
Fuente: Am J Med. 2004 Jan 15;116(2):91-5.
1. Ustun T, Privett M, Lecrubier Y, et al. Form, frequency and burden
of sleep problems in general health care: a report from the WHO
collaborative study on psychological problems in general health
care. Eur Psychiatry. 1996;11:1087-1096.
2. Ancoli-Israel S, Roth T. Characteristics of insomnia in the United
States: results of the 1991 national sleep foundation survey. I. Sleep.
1999;22(suppl):S347-S353.
3. Walsh J, Ustan Bedirhan T. Prevalence and health consequences of
insomnia. Sleep. 1999;22:427-436.
4. Zammit KG, Weiner J, Damato N, et al. Quality of life in people
with insomnia. Sleep. 1999;22(suppl):S379-S385.
5. Leger D, Guilleminault C, Dreyfus JP, et al. Prevalence of insomnia
in a survey of 12,778 adults in France. J Sleep Res. 2000;9:35-42.
6. Leger D, Scheuermaier K, Philip P, et al. SF-36: evaluation of quality
of life in severe and mild insomniacs compared with good sleepers.
Psychosom Med. 2001;63:49-55.
7. Carskadon MA, Dement WC, Mitler MM, et al. Self-reports versus
sleep laboratory findings in 122 drug-free subjects with complaints
of chronic insomnia. Am J Psychiatry. 1976;133:1382-1388.
8. McCall WV, Edinger JD. Subjective total insomnia: an example of
sleep state misperception. Sleep. 1992;15:71-73.
9. Laudon M, Zisapel N. Melatonin deficiency and its implications for
the treatment of insomnia in elderly subjects. Aging Male. 1998;1:
1-8.
10. Bojkowski CJ, Aldhous M, English J, et al. Suppression of nocturnal
plasma melatonin and 6-sulphatoxymelatonin by bright and dim
light in man. Horm Metab Res. 1987;19:437-440.
11. Sharma M, Palacios-Bois J, Schwartz G, et al. Circadian rhythms of
melatonin and cortisol in aging. Biol Psychiatry. 1989;25:305-319.
12. Nair NPV, Hariharasubramanian N, Pilapil C, et al. Plasma melatonin
-an index of brain aging in humans? Biol Psychiatry. 1986;
21:141-150.
13. Waldhauser F, Weiszenbacher G, Tatzer E, et al. Alternations in
nocturnal serum melatonin levels in humans with growth and aging.
J Clin Endocrinol Metab. 1988;66:648-652.
14. van Coevorden A, Mockel J, Laurent E, et al. Neuroendocrine
rhythms and sleep in aging men. Am J Physiol. 1991;260:E651-
E661.
15. Kennaway DJ, Lushington K, Dawson D, et al. Urinary 6-sulfatoxymelatonin
excretion and aging: new results and a critical review
of the literature. J Pineal Res. 1999;27:210-220.
16. Haimov I, Laudon M, Zisapel N, et al. Sleep disorders and melatonin
rhythms in elderly people. BMJ. 1994;309:167.
17. Zeitzer JM, Daniels JE, Duffy JF, et al. Do plasma melatonin concentrations
decline with age? Am J Med. 1999;107:432-436.
18. Czeisler CA, Dumont M, Duffy JF, et al. Association of sleep-wake
habits in older people with changes in output of circadian pacemaker.
Lancet. 1992;340:933-936.
19. MacFarlane J, Cleghorn J, Brown G. Melatonin and core temperature
rhythm in chronic insomnia. Adv Biosci. 1984;53:303-306.
20. 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.
21. Hajak G, Rodenbeck A, Adler L, et al. Nocturnal melatonin secretion
and sleep after doxepin administration in chronic primary insomnia.
Pharmacopsychiatry. 1996;29:187-192.
94 January 15, 2004 THE AMERICAN JOURNAL OF MEDICINE_ Volume 116
22. Lushington K, Lack L, Kennaway DJ, et al. 6-Sulfatoxymelatonin
excretion and self-reported sleep in good sleeping controls and 55-
80-year-old insomniacs. J Sleep Res. 1998;7:75-83.
23. 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;8:57-64.
24. Malik FS, Mehra MR, Ali A, et al. Nocturnal melatonin release
impairment and clinical effects of exogenous melatonin in chronic
heart failure. J Am Coll Cardiol. 1997;29(suppl A):370A.
25. Petterborg LJ, Thalen BE, Kjellman BF, Wetterberg L. Effect of melatonin
replacement on serum hormone rhythms in a patient lacking
endogenous melatonin. Brain Res Bull. 1991;27:181-185.
26. Garfinkel D, Laudon M, Nof D, Zisapel N. Improvement of sleep
quality in elderly people by controlled-release melatonin. Lancet.
1995;346:541-544.
27. Haimov I, Lavie P, Laudon M, et al. Melatonin replacement therapy
of elderly insomniacs. Sleep. 1995;18:598-603.
28. Wurtman RJ, Zhdanova I. Improvement of sleep quality by melatonin.
Lancet. 1995;346:1491.
29. van den Heuvel C, Reid K, Dawson D. Effect of atenolol on nocturnal
sleep and temperature in young men: reversal by pharmacological
doses of melatonin. Psychol Behav. 1997;61:795-802.
30. Hughes RJ, Sack R, Lewy A. The role of melatonin and circadian
phase in age-related sleep-maintenance insomnia: assessment in a
clinical trial of melatonin replacement. Sleep. 1998;21:52-68.
31. Kripke D, Elliot J, Youngstedt S, Smith J. Melatonin: marvel or
marker? Ann Med. 1998;30:81-87.
32. Youngstedt SD, Kripke DF, Elliott JA. Melatonin excretion is not
related to sleep in the elderly. J Pineal Res. 1998;24:142-145.
33. Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition
(DSM-IV). Washington, DC: American Psychiatric Association;
1994.
34. Lipman RS. Differentiating anxiety and depression in anxiety
disorders: use of rating scales. Psychopharmacol Bull. 1982;18:69-
77.
35. Raskin H, Schulterbrandt J, Reatig N, McKeon JJ. Replication of
factors of psychopathology in interview, ward behaviour and selfreport
ratings of hospitalised depressives. J Nerv Ment Dis. 1969;
148:87-98.
36. Kukull WA, Larson EB, Teri L, et al. The Mini-Mental State Examination
score and the clinical diagnosis of dementia. J Clin Epidemiol.
1994;47:1061-1067.
37. Luboshitzky R, Shen-Orr Z, Tzischichinsky O, et al. Actigraphic
sleep-wake patterns and urinary 6-sulfatoxymelatonin excretion in
patients with Alzheimer's disease. Chronobiol Int. 2001;18:513-524.
38. Cugini P, Touitou Y, Bogdan A, et al. Is melatonin circadian
rhythm a physiological feature associated with healthy longevity? A
study of long-living subjects and their progeny. Chronobiol Int.
2001;18:99-107.
39. Baskett JJ, Wood PC, Broad JB, et al. Melatonin in older people with
age-related sleep maintenance problems: a comparison with age
matched normal sleepers. Sleep. 2001;24:418-424.
40. Duffy JF, Zeitzer JM, Rimmer DW, et al. Peak of circadian melatonin
rhythm occurs later within the sleep of older subjects. Am J
Physiol Endocrinol Metab. 2002;282:E297-E303.
41. Arendt J, Bojkowski C, Franey C, et al. Immunoassay of 6-hydroxymelatonin
sulfate in human plasma and urine: abolition of
the urinary 24-hour rhythm with atenolol. J Clin Endocrinol Metab.
1985;60:1166-1173.
42. Zisapel N, Laudon M. Subjective assessment of the effects of CNSactive
drugs on sleep by the Leeds sleep evaluation questionnaire: a
review. Hum Psychopharmacol. 2003;18:1-20.
43. Graw P, Haug HJ, Leonhardt G, Wirz-Justice A. Sleep deprivation
response in seasonal affective disorder during a 40-h constant routine.
J Affect Disord. 1998;48:69-74.
44. Haug H, Fahndrich E. Problems in defining response in therapy
studies. Pharmacopsychiatry. 1986;19:1710-1711.
45. Powell CV, Kelly AM, Williams A. Determining the minimum clinically
significant difference in visual analog pain score for children.
Ann Emerg Med. 2001;37:28-31.
46. Brugger P, Markti W, Herold M. Impaired nocturnal secretion of
melatonin in coronary heart disease. Lancet. 1995;345:1408.
47. Sakotnik A, Liebmann PM, Stoschitzky K, et al. Decreased melatonin
synthesis in patients with coronary artery disease. Eur Heart J.
1999;20:1314-1317.
48. Girotti L, Lago M, Ianovsky O, et al. Low urinary 6-sulphatoxymelatonin
levels in patients with coronary artery disease. J Pineal
Res. 2000;29:138-142.
49. Wetterberg L, Bergiannaki JD, Paparrigopoulos T, et al. Normative
melatonin excretion: a multinational study. Psychoneuroendocrinology.
1999;24:209-226.
Nocturnal 6-Sulfatoxymelatonin Excretion in Insomnia/Leger et al