New developments in the treatment of primary insomnia in elderly patients: focus on prolonged-release melatonin

References

• Wilson SJ, Nutt DJ, Alford C, et al. British Association for Psychopharmacology consensus statement on evidence-based treatment of insomnia, parasomnias and circadian rhythm disorders. J Psychopharmacol. 2010;24:1577–1601.
   PubMed Web of Science ®Google Scholar
• Morin CM, Benca R. Chronic insomnia. Lancet. 2012;379:1129–1141.
   PubMed Web of Science ®Google Scholar
• Neikrug AB, Ancoli-Israel S. Sleep disorders in the older adult – a mini-review. Gerontology. 2010;56:181–189.
   PubMed Web of Science ®Google Scholar
• Wolkove N, Elkholy O, Baltzan M, Palayew M. Sleep and aging: 1. Sleep disorders commonly found in older people. CMAJ. 2007;176:1299–1304.
   PubMed Web of Science ®Google Scholar
• Wolkove N, Elkholy O, Baltzan M, Palayew M. Sleep and aging: 2. Management of sleep disorders in older people. CMAJ. 2007;176:1449–1454.
   PubMed Web of Science ®Google Scholar
• Fetveit A. Late-life insomnia: a review. Geriatr Gerontol Int. 2009;9:220–234.
   PubMed Web of Science ®Google Scholar
• Boyle N, Naganathan V, Cumming RG. Medication and falls: risk and optimization. Clin Geriatr Med. 2010;26:583–605.
   PubMed Web of Science ®Google Scholar
• Faught E. Monotherapy in adults and elderly persons. Neurology. 2007;69:S3–S9.
   PubMed Web of Science ®Google Scholar
• Wills P Claesson CB, Fratiglioni L, Fastbom J, Thorslund M, Winblad B. Drug use by demented and non-demented elderly people. Age Ageing. 1997;26:383–391.
   PubMed Web of Science ®Google Scholar
• Zisapel N. Melatonin and sleep. Open Neuroendocr J. 2010;3:85–95.
   Google Scholar
• Pandi-Perumal SR, Srinivasan V, Spence W, Cardinali DP. Role of the melatonin system in the control of sleep: therapeutic implications. CNS Drugs. 2007;121:995–1018.
   Google Scholar
• Cardinali DP, Srinivasan V, Brzezinski A, Brown GM. Melatonin and its analogs in insomnia and depression. J Pineal Res. 2012;52:365–375.
   PubMed Web of Science ®Google Scholar
• Lavie P. Melatonin: role in gating nocturnal rise in sleep propensity. J Biol Rhythms. 1997;12:657–665.
   PubMed Web of Science ®Google Scholar
• Haimov I, Laudon M, Zisapel N, et al. Sleep disorders and melatonin rhythms in elderly people. BMJ. 1994;309:167.
   PubMed Web of Science ®Google Scholar
• Hughes RJ, Badia P. Sleep-promoting and hypothermic effects of daytime melatonin administration in humans. Sleep. 1997;20:124–131.
   PubMed Web of Science ®Google Scholar
• 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;116:91–95.
   PubMed Web of Science ®Google Scholar
• Zhdanova IV Wurtman RJ, Regan MM, Taylor JA, Shi JP, Leclair OU. Melatonin treatment for age-related insomnia. J Clin Endocrinol Metab. 2001;86:4727–4730.
   PubMed Web of Science ®Google Scholar
• Arendt J, Skene DJ, Middleton B, Lockley SW, Deacon S. Efficacy of melatonin treatment in jet lag, shift work, and blindness. J Biol Rhythms. 1997;12:604–617.
   PubMed Web of Science ®Google Scholar
• Srinivasan V Singh J, Pandi-Perumal SR, Brown GM, Spence DW, Cardinali DP. Jet lag, circadian rhythm sleep disturbances, and depression: the role of melatonin and its analogs. Adv Ther. 2010;27:796–813.
   PubMed Web of Science ®Google Scholar
• Turek FW, Gillette MU. Melatonin, sleep, and circadian rhythms: rationale for development of specific melatonin agonists. Sleep Med. 2004;5:523–532.
   PubMed Web of Science ®Google Scholar
• Mandrioli R, Mercolini L, Raggi MA. Metabolism of benzodiazepine and non-benzodiazepine anxiolytic-hypnotic drugs: an analytical point of view. CurrDrugMetab. 2010;11:815–829.
   Google Scholar
• Sigel E, Luscher BP. A closer look at the high affinity benzodiazepine binding site on GABAA receptors. Curr Top Med Chem. 2011;11:241–246.
   Web of Science ®Google Scholar
• Nowell PD, Mazumdar S, Buysse DJ, Dew MA, Reynolds CF, III, Kupfer DJ. Benzodiazepines and zolpidem for chronic insomnia: a meta-analysis of treatment efficacy. JAMA. 1997;278:2170–2177.
   PubMed Web of Science ®Google Scholar
• Morin AK, Willett K. The role of eszopiclone in the treatment of insomnia. Adv Ther. 2009;26:500–518.
   PubMed Web of Science ®Google Scholar
• Morin AK. Strategies for treating chronic insomnia. Am J Manag Care. 2006;12:S230–S245.
   PubMed Web of Science ®Google Scholar
• Rosenberg RP. Sleep maintenance insomnia: strengths and weaknesses of current pharmacologic therapies. Ann Clin Psychiatry. 2006;18:49–56.
   PubMedGoogle Scholar
• Ancoli-Israel S, Richardson GS, Mangano RM, Jenkins L, Hall P, Jones WS. Long-term use of sedative hypnotics in older patients with insomnia. Sleep Med. 2005;6:107–113.
   PubMed Web of Science ®Google Scholar
• Montplaisir J, Hawa R, Moller H, et al. Zopiclone and zaleplon vs benzodiazepines in the treatment of insomnia: Canadian consensus statement. Hum Psychopharmacol. 2003;18:29–38.
   PubMed Web of Science ®Google Scholar
• Hair PI, McCormack PL, Curran MP. Eszopiclone: a review of its use in the treatment of insomnia. Drugs. 2008;68:1415–1434.
   Web of Science ®Google Scholar
• Zammit G. Comparative tolerability of newer agents for insomnia. Drug Saf. 2009;32:735–748.
   PubMed Web of Science ®Google Scholar
• Vollrath L, Semm P, Gammel G. Sleep induction by intranasal administration of melatonin. Adv Biosci. 1981;29:327–329.
   Google Scholar
• Waldhauser F, Saletu B, Trinchard-Lugan I. Sleep laboratory investigations on hypnotic properties of melatonin. Psychopharmacology (Berl). 1990;100:222–226.
   PubMed Web of Science ®Google Scholar
• Zhdanova IV. Melatonin as a hypnotic: pro. Sleep Med Rev. 2005;9:51–65.
   PubMed Web of Science ®Google Scholar
• Srinivasan V, Pandi-Perumal SR, Trahkt I, et al. Melatonin and mela- tonergic drugs on sleep: possible mechanisms of action. Int J Neurosci. 2009;119:821–846.
   PubMed Web of Science ®Google Scholar
• Buscemi N, Vandermeer B, Hooton N, et al. Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis. BMJ. 2006;332:385–393.
   PubMed Web of Science ®Google Scholar
• Brzezinski A, Vangel MG, Wurtman RJ, et al. Effects of exogenous melatonin on sleep: a meta-analysis. Sleep Med Rev. 2005;9:41–50.
   PubMed Web of Science ®Google Scholar
• 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;91:1824–1828.
   PubMed Web of Science ®Google Scholar
• 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;19:423–431.
   PubMed Web of Science ®Google Scholar
• Gorfine T, Assaf Y, Goshen-Gottstein Y, Yeshurun Y, Zisapel N. Sleep-anticipating effects of melatonin in the human brain. Neuroimage. 2006;31:410–418.
   PubMed Web of Science ®Google Scholar
• Hardeland R, Cardinali DP, Srinivasan V, Spence DW, Brown GM, Pandi-Perumal SR. Melatonin – a pleiotropic, orchestrating regulator molecule. ProgNeurobiol. 2011;93:350–384.
   Google Scholar
• Cardinali DP, Lynch HJ, Wurtman RJ. Binding of melatonin to human and rat plasma proteins. Endocrinology. 1972;91:1213–1218.
   PubMed Web of Science ®Google Scholar
• Claustrat B, Brun J, Chazot G. The basic physiology and pathophysiology of melatonin. Sleep Med Rev. 2005;9:11–24.
   PubMed Web of Science ®Google Scholar
• Tetsuo M, Markey SP, Kopin IJ. Measurement of 6-hydroxymelatonin in human urine and its diurnal variations. Life Sci. 1980;27:105–109.
   PubMed Web of Science ®Google Scholar
• Ma X, Idle JR, Krausz KW, Gonzalez FJ. Metabolism of melatonin by human cytochromes p450. Drug Metab Dispos. 2005;33:489–494.
   PubMed Web of Science ®Google Scholar
• Ferry G, Ubeaud C, Lambert PH, et al. Molecular evidence that melatonin is enzymatically oxidized in a different manner than tryptophan: investigations with both indoleamine 2,3-dioxygenase and myeloperoxidase. Biochem J. 2005;388:205–215.
   PubMed Web of Science ®Google Scholar
• Cardinali DP, Vacas MI, Boyer EE. Specific binding of melatonin in bovine brain. Endocrinology. 1979;105:437–441.
   PubMed Web of Science ®Google Scholar
• Niles LP, Wong YW, Mishra RK, Brown GM. Melatonin receptors in brain. Eur J Pharmacol. 1979;55:219–220.
   PubMed Web of Science ®Google Scholar
• Morgan PJ, Barrett P, Howell HE, Helliwell R. Melatonin receptors: localization, molecular pharmacology and physiological significance. Neurochem Int. 1994;24:101–146.
   PubMed Web of Science ®Google Scholar
• Reppert SM, Weaver DR, Ebisawa T. Cloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses. Neuron. 1994;13:1177–1185.
   PubMed Web of Science ®Google Scholar
• Reppert SM, Godson C, Mahle CD, Weaver DR, Slaugenhaupt SA, Gusella JF. Molecular characterization of a second melatonin receptor expressed in human retina and brain: the Mel1b melatonin receptor. Proc Natl Acad Sci U S A. 1995;92:8734–8738.
   PubMed Web of Science ®Google Scholar
• Dubocovich ML, Delagrange P, Krause DN, Sugden D, Cardinali DP, Olcese J. International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, classification, and pharmacology of G proteincoupled melatonin receptors. Pharmacol Rev. 2010;62:343–380.
   PubMed Web of Science ®Google Scholar
• Pandi-Perumal SR, Trakht I, Srinivasan V et al. Physiological effects of melatonin: role of melatonin receptors and signal transduction pathways. Prog Neurobiol. 2008;185:335–353.
   Google Scholar
• 3. Weaver DR, Reppert SM. The Mel1a melatonin receptor gene is expressed in human suprachiasmatic nuclei. Neuroreport. 1996;8:109–112.
   PubMed Web of Science ®Google Scholar
• Wu YH, Zhou JN, Van Heerikhuize J, Jockers R, Swaab DF. Decreased MT1 melatonin receptor expression in the suprachiasmatic nucleus in aging and Alzheimer’s disease. Neurobiol Aging. 2007;28:1239–1247.
   PubMed Web of Science ®Google Scholar
• Liu C, Weaver DR, Jin X, et al. Molecular dissection of two distinct actions of melatonin on the suprachiasmatic circadian clock. Neuron. 1997;19:91–102.
   PubMed Web of Science ®Google Scholar
• von Gall C, Stehle JH, Weaver DR. Mammalian melatonin receptors: molecular biology and signal transduction. Cell Tissue Res. 2002;309:151–162.
   PubMed Web of Science ®Google Scholar
• Lewy AJ, Ahmed S, Jackson JM, Sack RL. Melatonin shifts human circadian rhythms according to a phase-response curve. Chronobiol Int. 1992;9:380–392.
   PubMed Web of Science ®Google Scholar
• Burgess HJ, Revell VL, Eastman CI. A three pulse phase response curve to three milligrams of melatonin in humans. J Physiol. 2008;586:639–647.
   PubMed Web of Science ®Google Scholar
• Weaver DR, Liu C, Reppert SM. Nature’s knockout: the Mel1b receptor is not necessary for reproductive and circadian responses to melatonin in Siberian hamsters. Mol Endocrinol. 1996;10:1478–1487.
   PubMedGoogle Scholar
• Masana MI, Sumaya IC, Becker-Andre M, Dubocovich ML. Behavioral characterization and modulation of circadian rhythms by light and melatonin in C3H/HeN mice homozygous for the RORbeta knockout. Am J Physiol Regul Integr Comp Physiol. 2007;292:R2357–R2367.
   Web of Science ®Google Scholar
• Saper CB, Fuller PM, Pedersen NP, Lu J, Scammell TE. Sleep state switching. Neuron. 2010;68:1023–1042.
   PubMed Web of Science ®Google Scholar
• Jan JE, Reiter RJ, Wasdell MB, Bax M. The role of the thalamus in sleep, pineal melatonin production, and circadian rhythm sleep disorders. J Pineal Res. 2009;46:1–7.
   PubMed Web of Science ®Google Scholar
• Golombek DA, Escolar E, Burin LJ, Brito Sanchez MG, Fernandez DD, Cardinali DP. Chronopharmacology of melatonin: inhibition by benzodiazepine antagonism. Chronobiol Int. 1992;9:124–131.
   PubMed Web of Science ®Google Scholar
• Golombek DA, Fernandez DD, Brito Sanchez MG, Burin L, Cardinali DP. Time-dependent anticonvulsant activity of melatonin in hamsters. Eur J Pharmacol. 1992;210:253–258.
   PubMed Web of Science ®Google Scholar
• Golombek DA, Pevet P, Cardinali DP. Melatonin effects on behavior: possible mediation by the central GABAergic system. Neurosci Biobehav Rev. 1996;20:403–412.
   PubMed Web of Science ®Google Scholar
• Munoz-Hoyos A, Sanchez-Forte M, Molina-Carballo A, et al. Melatonin’s role as an anticonvulsant and neuronal protector: experimental and clinical evidence. J Child Neurol. 1998;13:501–509.
   Google Scholar
• Molina-Carballo A, Munoz-Hoyos A, Sanchez-Forte M, Uberos- Fernandez J, Moreno-Madrid F, Acuna-Castroviejo D. Melatonin increases following convulsive seizures may be related to its anticonvulsant properties at physiological concentrations. Neuropediatrics. 2007;38:122–125.
   PubMed Web of Science ®Google Scholar
• Solmaz I, Gurkanlar D, Gokcil Z, Goksoy C, Ozkan M, Erdogan E. Antiepileptic activity of melatonin in guinea pigs with pentylenetetrazol- induced seizures. Neurol Res. 2009;31:989–995.
   PubMed Web of Science ®Google Scholar
• Cardinali DP, Pandi-Perumal SR, Niles LP Melatonin and its receptors: biological function in circadian sleep-wake regulation. In: Monti JM, Pandi-Perumal SR, Sinton CM, editors. Neurochemistry of Sleep and Wakefulness. Cambridge, UK: Cambridge University Press; 2008.
   Google Scholar
• Fenoglio-Simeone K, Mazarati A, Sefidvash-Hockley S, et al. Anticonvulsant effects of the selective melatonin receptor agonist ramelteon. Epilepsy Behav. 2009;16:52–57.
   Web of Science ®Google Scholar
• Golombek DA, Martini M, Cardinali DP. Melatonin as an anxiolytic in rats: time dependence and interaction with the central GABAergic system. Eur J Pharmacol. 1993;237:231–236.
   PubMed Web of Science ®Google Scholar
• Golombek DA, Escolar E, Burin LJ, Brito Sanchez MG, Cardinali DP Time-dependent melatonin analgesia in mice: inhibition by opiate or benzodiazepine antagonism. Eur J Pharmacol. 1991;194:25–30.
   Web of Science ®Google Scholar
• Golombek DA, Escolar E, Cardinali DP. Melatonin-induced depression of locomotor activity in hamsters: time dependency and inhibition by the central type benzodiazepine antagonist Ro 15–1788. Physiol Behav. 1991;49:1091–1098.
   PubMed Web of Science ®Google Scholar
• Pang CS, Tsang SF, Yang JC. Effects of melatonin, morphine and diazepam on formalin-induced nociception in mice. Life Sci. 2001;68:943–951.
   PubMed Web of Science ®Google Scholar
• Papp M, Litwa E, Gruca P, Mocaer E. Anxiolytic-like activity of agomelatine and melatonin in three animal models of anxiety. Behav Pharmacol. 2006;17:9–18.
   PubMed Web of Science ®Google Scholar
• Ulugol A, Dokmeci D, Guray G, Sapolyo N, Ozyigit F, Tamer M. Antihyperalgesic, but not antiallodynic, effect of melatonin in nerve- injured neuropathic mice: possible involvements of the L-arginine-NO pathway and opioid system. Life Sci. 2006;78:1592–1597.
   Web of Science ®Google Scholar
• Srinivasan V Pandi-Perumal SR, Spence DW, et al. Potential use of melatonergic drugs in analgesia: mechanisms of action. Brain Res Bull. 2010;81:362–371.
   PubMed Web of Science ®Google Scholar
• Garfinkel D, Laudon M, Nof D, Zisapel N. Improvement of sleep quality in elderly people by controlled-release melatonin. Lancet. 1995;346:541–544.
   PubMed Web of Science ®Google Scholar
• Garfinkel D, Laudon M, Zisapel N. Improvement of sleep quality by con- trolled-release melatonin in benzodiazepine-treated elderly insomniacs. Arch Gerontol Geriatr. 1997;24:223–231.
   PubMed Web of Science ®Google Scholar
• Fainstein I, Bonetto A, Brusco LI, Cardinali DP. Effects of melatonin in elderly patients with sleep disturbance. A pilot study. Curr Ther Res. 1997;58:990–1000.
   Web of Science ®Google Scholar
• Dagan Y, Zisapel N, Nof D, Laudon M, Atsmon J. Rapid reversal of tolerance to benzodiazepine hypnotics by treatment with oral melatonin: a case report. Eur Neuropsychopharmacol. 1997;7:157–160.
   PubMed Web of Science ®Google Scholar
• Garfinkel D, Zisapel N, Wainstein J, Laudon M. Facilitation of benzodiazepine discontinuation by melatonin: a new clinical approach. Arch Intern Med. 1999;159:2456–2460.
   PubMed Web of Science ®Google Scholar
• Siegrist C, Benedetti C, Orlando A, et al. 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;30:34–42.
   PubMed Web of Science ®Google Scholar
• Vissers FH, Knipschild PG, Crebolder HF. Is melatonin helpful in stopping the long-term use of hypnotics? A discontinuation trial. Pharm World Sci. 2007;29:641–646.
   PubMed Web of Science ®Google Scholar
• Cardinali DP Gvozdenovich E, Kaplan MR, et al. A double blind-placebo controlled study on melatonin efficacy to reduce anxiolytic benzodiazepine use in the elderly. Neuro Endocrinol Lett. 2002;23:55–60.
   PubMed Web of Science ®Google Scholar
• Kunz D, Bineau S, Maman K, Milea D, Toumi M. Benzodiazepine discontinuation with prolonged-release melatonin: hints from a German longitudinal prescription database. Expert Opin Pharmacother. 2012;13:9–16.
   PubMed Web of Science ®Google Scholar
• Lemoine P, Nir T, Laudon M, Zisapel N. Prolonged-release melatonin improves sleep quality and morning alertness in insomnia patients aged 55 years and older and has no withdrawal effects. J Sleep Res. 2007;16:372–380.
   PubMed Web of Science ®Google Scholar
• Wade AG, Ford I, Crawford G, et al. Efficacy of prolonged release melatonin in insomnia patients aged 55–80 years: quality of sleep and next-day alertness outcomes. Curr Med Res Opin. 2007;23:2597–2605.
   PubMed Web of Science ®Google Scholar
• Wade AG, Ford I, Crawford G, et al. Nightly treatment of primary insomnia with prolonged release melatonin for 6 months: a randomized placebo controlled trial on age and endogenous melatonin as predictors of efficacy and safety. BMC Med. 2010;8:51.
   PubMed Web of Science ®Google Scholar
• Lemoine P, Garfinkel D, Laudon M, Nir T, Zisapel N. Prolonged- release melatonin for insomnia – an open-label long-term study of efficacy, safety, and withdrawal. Ther Clin Risk Manag. 2011;7:301–311.
   PubMed Web of Science ®Google Scholar
• Luthringer R, Muzet M, Zisapel N, Staner L. The effect of prolonged- release melatonin on sleep measures and psychomotor performance in elderly patients with insomnia. Int Clin Psychopharmacol. 2009;24:239–249.
   PubMed Web of Science ®Google Scholar
• Garfinkel D, Zorin M, Wainstein J, Matas Z, Laudon M, Zisapel N. Efficacy and safety of prolonged-release melatonin in insomnia patients with diabetes: a randomized, double-blind, crossover study. Diabetes Metab Syndr Obes. 2011;4:307–313.
   PubMedGoogle Scholar
• Cardinali DP, Cano P, Jimenez-Ortega V, Esquifino AI. Melatonin and the metabolic syndrome. Physiopathologic and therapeutical implications. Neuroendocrinology. 2011;93:133–142.
   PubMed Web of Science ®Google Scholar
• Tutuncu NB, Batur MK, Yildirir A, et al. Melatonin levels decrease in type 2 diabetic patients with cardiac autonomic neuropathy. J Pineal Res. 2005;39:43–49.
   Web of Science ®Google Scholar
• Peschke E, Stumpf I, Bazwinsky I, Litvak L, Dralle H, Muhlbauer E. Melatonin and type 2 diabetes – a possible link? J Pineal Res. 2007;42:350–358.
   PubMed Web of Science ®Google Scholar
• Prokopenko I, Langenberg C, Florez JC, et al. Variants in MTNR1B influence fasting glucose levels. Nat Genet. 2009;41:77–81.
   PubMed Web of Science ®Google Scholar
• Sakotnik A, Liebmann PM, Stoschitzky K, et al. Decreased melatonin synthesis in patients with coronary artery disease. Eur Heart J. 1999;20:1314–1317.
   PubMed Web of Science ®Google Scholar
• Yaprak M, Altun A, Vardar A, Aktoz M, Ciftci S, Ozbay G. Decreased nocturnal synthesis of melatonin in patients with coronary artery disease. Int J Cardiol. 2003;89:103–107.
   Web of Science ®Google Scholar
• Girotti L, Lago M, Ianovsky O, et al. Low urinary 6-sulphatoxyme- latonin levels in patients with coronary artery disease. J Pineal Res. 2000;29:138–142.
   PubMed Web of Science ®Google Scholar
• Dominguez-Rodriguez A, Abreu-Gonzalez P, Garcia MJ, Sanchez J, Marrero F, Armas-Trujillo D. Decreased nocturnal melatonin levels during acute myocardial infarction. J Pineal Res. 2002;33:248–252.
   PubMed Web of Science ®Google Scholar
• Scheer FA, Van Montfrans GA, Van Someren EJ, Mairuhu G, Buij s RM. Daily nighttime melatonin reduces blood pressure in male patients with essential hypertension. Hypertension. 2004;43:192–197.
   PubMed Web of Science ®Google Scholar
• Cagnacci A, Cannoletta M, Renzi A, Baldassari F, Arangino S, Volpe A. Prolonged melatonin administration decreases nocturnal blood pressure in women. Am J Hypertens. 2005;18:1614–1618.
   PubMed Web of Science ®Google Scholar
• Grossman E, Laudon M, Yalcin R, et al. Melatonin reduces night blood pressure in patients with nocturnal hypertension. Am J Med. 2006;119:898–902.
   PubMed Web of Science ®Google Scholar
• Cavallo A, Daniels SR, Dolan LM, Bean JA, Khoury JC. Blood pressure-lowering effect of melatonin in type 1 diabetes. J Pineal Res. 2004;36:262–266.
   PubMed Web of Science ®Google Scholar
• Tamura H, Nakamura Y, Narimatsu A, et al. Melatonin treatment in peri- and postmenopausal women elevates serum high-density lipoprotein cholesterol levels without influencing total cholesterol levels. J Pineal Res. 2008;45:101–105.
   PubMed Web of Science ®Google Scholar
• Kozirog M, Poliwczak AR, Duchnowicz P, Koter-Michalak M, Sikora J, Broncel M. Melatonin treatment improves blood pressure, lipid profile, and parameters of oxidative stress in patients with metabolic syndrome. J Pineal Res. 2011;50:261–266.
   PubMed Web of Science ®Google Scholar
• Dolev Z. Case series of perimenopausal women with insomnia treated with mirtazapine followed by prolonged-release melatonin add-on and monotherapy. Arch Womens Ment Health. 2011;14:269–273.
   PubMed Web of Science ®Google Scholar
• Otmani S, Demazieres A, Staner C, et al. Effects of prolonged-release melatonin, zolpidem, and their combination on psychomotor functions, memory recall, and driving skills in healthy middle aged and elderly volunteers. Hum Psychopharmacol. 2008;23:693–705.
   PubMed Web of Science ®Google Scholar
• Otmani S, Metzger D, Guichard N, et al. Effects of prolonged-release melatonin and zolpidem on postural stability in older adults. Hum Psychopharmacol. 2012;27:270–276.
   PubMed Web of Science ®Google Scholar
• Neri B, de Leonardis V Gemelli MT, et al. Melatonin as biological response modifier in cancer patients. Anticancer Res. 1998;18:1329–1332.
   Web of Science ®Google Scholar
• Weishaupt JH, Bartels C, Polking E, et al. Reduced oxidative damage in ALS by high-dose enteral melatonin treatment. J Pineal Res. 2006;41:313–323.
   PubMed Web of Science ®Google Scholar
• Chahbouni M, Escames G, Venegas C, et al. Melatonin treatment normalizes plasma pro-inflammatory cytokines and nitrosative/oxidative stress in patients suffering from Duchenne muscular dystrophy. J Pineal Res. 2010;48:282–289.
   PubMed Web of Science ®Google Scholar
• Waldhauser F, Waldhauser M, Lieberman HR, Deng MH, Lynch HJ, Wurtman RJ. Bioavailability of oral melatonin in humans. Neuroendocrinology. 1984;39:307–313.
   PubMed Web of Science ®Google Scholar
• Voordouw BC, Euser R, Verdonk RE, et al. Melatonin and melatonin- progestin combinations alter pituitary-ovarian function in women and can inhibit ovulation. J Clin Endocrinol Metab. 1992;74:108–117.
   PubMed Web of Science ®Google Scholar
• Nickkholgh A, Schneider H, Sobirey M, et al. The use of high-dose melatonin in liver resection is safe: first clinical experience. J Pineal Res. 2011;50:381–388.
   PubMed Web of Science ®Google Scholar
• Jou MJ, Peng TI, Hsu LF, et al. Visualization of melatonin’s multiple mitochondrial levels of protection against mitochondrial Ca2+-mediated permeability transition and beyond in rat brain astrocytes. J Pineal Res. 2010;48:20–38.
   PubMed Web of Science ®Google Scholar
• Jou MJ. Melatonin preserves the transient mitochondrial permeability transition for protection during mitochondrial Ca2+ stress in astrocyte. J Pineal Res. 2011;50:427–435.
   Web of Science ®Google Scholar
• Peng TI, Hsiao CW, Reiter RJ, Tanaka M, Lai YK, Jou MJ. mtDNA T8993G mutation-induced mitochondrial complex V inhibition augments cardiolipin-dependent alterations in mitochondrial dynamics during oxidative, Ca2+, and lipid insults in NARP cybrids: a potential therapeutic target for melatonin. J Pineal Res. 2012;52:93–106.
   PubMed Web of Science ®Google Scholar
• Solomon DA, Leon AC, Endicott J, et al. Psychosocial impairment and recurrence of major depression. Compr Psychiatry. 2004;45:423–430.
   PubMed Web of Science ®Google Scholar
• Pandi-Perumal SR, Bahammam AS, Brown GM, et al. Melatonin antioxidative defense: therapeutic implications for aging and neurodegenerative processes. Neurotoxicity Res. June 28, 2012. [Epub ahead of print.]
   Web of Science ®Google Scholar