Role of melatonin in mood disorders and the antidepressant effects of agomelatine

Expert Opinion on Investigational Drugs

Volumn 21, Issue 10, 2012, Pages 1503-1522

  Srinivasan, Venkataramanujam ^a   De Berardis, Domenico ^b   Shillcutt, Samuel D ^c   Brzezinski, Amnon ^d  

^a Sri Sathya Sai Medical Educational and Research Foundation   (India)

^b Department of Neurosciences and Imaging University ^*  (Italy)

^c MERCER UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d HEBREW UNIVERSITY   (Israel)

Author keywords

Agomelatine; Depression; Insomnia chronobiotic; Melatonin; Mood disorders; Sleep

Indexed keywords

ACTIVITY REGULATED CYTOSKELETON ASSOCIATED PROTEIN; ADENYLATE CYCLASE; AGOMELATINE; AMFEBUTAMONE; CALMODULIN; DESIPRAMINE; ESCITALOPRAM; FLUOXETINE; IMIPRAMINE; LITHIUM SALT; MELATONIN; MELATONIN 1 RECEPTOR; MELATONIN 2 RECEPTOR; MONOAMINE OXIDASE INHIBITOR; PAROXETINE; PROTEIN KINASE C; RETINOIC ACID RECEPTOR ALPHA; RETINOIC ACID RECEPTOR BETA; SEROTONIN 1 RECEPTOR; SEROTONIN 2A RECEPTOR; SEROTONIN NORADRENALIN REUPTAKE INHIBITOR; SEROTONIN UPTAKE INHIBITOR; SERTRALINE; TRICYCLIC ANTIDEPRESSANT AGENT; VALPROMIDE; VENLAFAXINE;

ABDOMINAL PAIN; ADJUVANT THERAPY; AMYGDALOID NUCLEUS; ANXIETY; BASAL GANGLION; BIPOLAR DEPRESSION; BIPOLAR I DISORDER; BIPOLAR II DISORDER; BRAIN CORTEX; CALCIUM CELL LEVEL; CIRCADIAN RHYTHM; CLINICAL GLOBAL IMPRESSION SCALE; DEXAMETHASONE SUPPRESSION TEST; DIARRHEA; DIZZINESS; DRUG EFFICACY; DRUG HALF LIFE; DRUG METABOLISM; DRUG SAFETY; DRUG TOLERABILITY; DSM-IV; ENZYME ACTIVITY; GENERALIZED ANXIETY DISORDER; HAMILTON SCALE; HEADACHE; HIPPOCAMPUS; HORMONE BLOOD LEVEL; HUMAN; HYPERTRANSAMINASEMIA; MAJOR DEPRESSION; OBSESSIVE COMPULSIVE DISORDER; PATIENT COMPLIANCE; PROTEIN EXPRESSION; RANDOMIZED CONTROLLED TRIAL (TOPIC); REMISSION; REVIEW; SEASONAL AFFECTIVE DISORDER; SEXUAL DYSFUNCTION; SEXUAL FUNCTION; SIDE EFFECT; SLEEP DISORDER; SLEEP WAKING CYCLE; UNSPECIFIED SIDE EFFECT;

ACETAMIDES; ANIMALS; ANTIDEPRESSIVE AGENTS; HUMANS; MELATONIN; MOOD DISORDERS;

EID: 84866526491     PISSN: 13543784     EISSN: 17447658     Source Type: Journal    
DOI: 10.1517/13543784.2012.711314     Document Type: Review

References (145)

1. Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause 1990-2020: global burden of disease study. Lancet 1997;349:1498-504 (Pubitemid 27216360)
2. Lopez AD, Mathers CD, Ezzati M, et al. Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet 2006;367:1747-57 (Pubitemid 43767064)
3. Mykletun A, Bjerkeset O, Dewey M, et al. Anxiety, depression, and cause-specific mortality: the HUNT study. Psychosom Med 2007;69(4):323-31 (Pubitemid 46800292)
4. Mykletun A, Bjekeset O, Overland S, et al. Levels of anxiety and depression as predictors of mortality: the HUNT study. Br J Psychiatry 2009;195(2):118-25
5. Testa G, Cacciatore F, Galizia G, et al. Depressive symptoms predict mortality in elderly subjects with chronic heart failure. Eur J Clin Invest 2011;41(12):1310-17
6. Markkula N, Harkanen T, Perala J, et al. Mortality in people with depressive, anxiety and alcohol use disorders in Finland. Br J Psychiatry 2012;200:143-9
7. Patten SB, Williams JV, Lavorato D, et al. Mortality associated with major depression in a Canadian community cohort. Can J Psychiatry 2011;56:658-66
8. Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause, 1990-2020: global burden of disease study. Lancet 1997;349:1498-504 (Pubitemid 27216360)
9. 2A receptors in depression. J Psychiatry Neurosci 2004;29:252-65 (Pubitemid 39185866)
10. Sen S, Sanacora G. Major depression: emerging therapeutics. Mt Sinai J Med 2008;75:204-25
11. Nestler EJ, Barrot M, De Leone RJ, et al. Neurobiology of depression. Neuron 2002;34:13-25 (Pubitemid 34270695)
12. Germain A, Kupfer DJ. Circadian rhythm disturbances in depression. Hum Psychopharmacol 2008;23:571-85
13. Srinivasan V, Pandi-Perumal SR, Trakht I, et al. Pathophysiology of depression: role of sleep and the melatonergic system. Psychiat Res 2009;201-14
14. Riemann D, Berger M, Voderholzer U. Sleep and depression: results from psycho-biological studies. Biol Psychol 2001;57:67-103 (Pubitemid 32651895)
15. Roberts RE, Shema SJ, Kaplan GA, et al. Sleep complaints and depression in an aging cohort: a prospective perspective. Am J Psychiatry 2000;157:81-8 (Pubitemid 30027425)
16. Dijk DJ, Czeisler CA. Contribution of the circadian pacemaker and the sleep homeostat to sleep propensity, sleep structure, electroencephalographic slow waves and sleep spindle activity in humans. J Neurosci 1995;15:3526-38
17. Lustberg L, Reynolds CE. Depression and insomnia: questions of cause and effect. Sleep Med Rev 2000;4:253-62 (Pubitemid 30416008)
18. Moore RY, Klein DC. Visual pathways and the central neural control of a circadian rhythm in pineal serotonin N-acetyltransferase activity. Brain Res 1974;71:17-33
19. Sadun AA, Schaechter JD, Smith LE. A retino hyothalamic pathway in man: light mediation of circadian rhythms. Brain Res 1984;302:371-7 (Pubitemid 14077767)
20. Kripke DF, Mullaney DJ, Atkinson M, et al. Circadian rhythm disorders in manic-depressives. Biol Psychiatry 1978;13:335-51 (Pubitemid 8359217)
21. Kripke DF, Risch SC, Janowsky D. Bright white light alleviates depression. Psychiat Res 1983;10:105-12 (Pubitemid 14248059)
22. Wetterberg L. Melatonin in adult depression. In: Shafii M, Shafii SL. editors Melatonin in psychiatric and neoplastic disorders. American Psychiatry Press; Washington DC: 1998. p. 43-79
23. Lewy AJ, Sack RL, Cutler NL, et al. Melatonin in circadian phase sleep and mood disorders. In: Shafii M, Shafii SL. editors Melatonin in psychiatric and neoplastic disorders. American Psychiatry Press; Washington DC: 1998. p. 81-104
24. Berton O, Nestler EJ. New approaches to antidepressant drug discovery: beyond monoamines. Nat Rev Neurosci 2006;7:137-51 (Pubitemid 43151600)
25. Reppert SM, Weaver DR, Ebisawa T. Cloning and characterization of mammalian melatonin receptor that mediates reproductive and circadian responses. Neuron 1994;13:1177-85 (Pubitemid 24372135)
26. Reppert SM, Godson C, Mahle CD, et al. Molecular characterization of a second melatonin receptor expressed in human retina and brain: the MelIb melatonin receptor. Proc Natl Acad Sci USA 1995;92:8734-8
27. Dubocovich ML, Cardinali DP, Delagrange P, et al. Melatonin receptors. In: IUPHAR, editor The IUPHAR compendium of receptor characterization and classification. 2nd edition. IUPHAR Media; 2000. p. 271-7
28. 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 (Pubitemid 27332996)
29. Pandi-Perumal SR, Trakht I, Srinivasan V, et al. Physiological effects of melatonin: role of melatonin receptors and signal transduction pathways. Progr Neurobiol 2008;88:264-71
30. Morgan PJ, Barrett P, Howell HE, et al. Melatonin receptors: localization, molecular pharmacology and physiological significance. Neurochem Int 1994;8:101-46 (Pubitemid 24061864)
31. Bouton JA, Audinot V, Ferry G, et al. Molecular tools to study melatonin pathways and actions. Trends Pharmacol Sci 2005;26:412-19 (Pubitemid 41039217)
32. q/11 proteins. Mol Endocrinol 1999;13:2025-38 (Pubitemid 30637264)
33. Sampson SR, Lupowitz Z, Braiman L, et al. Role of protein kinase C alpha in melatonin signal transduction. Mol Cell Endocrinol 2006;252:82-7
34. Rivera-Bermudez MA, Gerdin MJ, Earnest DJ, et al. Regulation of basal rhythmicity in protein kinase C activity by melatonin in immortalized rat suprachiasmatic nucleus cells. Neurosci Lett 2003;346:37-40 (Pubitemid 36792188)
35. Benitez-King G. Melatonin as a cytoskeletal modulator: implications for cell physiology and disease. J Pineal Res 2006;40:1-9
36. Wiesenberg I, Missbach M, Kahlen JP, et al. Transcriptional activation of the nuclear receptor RZRa by the pineal gland hormone melatonin and identification of CGP 52608 as a synthetic ligand. Nucleic Acid Res 1995;23:327-33
37. Wirz-Justice A, Arendt J. Diurnal, menstrual cycle and seasonal indole rhythms in man and their modifications in affective disorders. In: Obiols J, Ballus C, Gonzales Monclyus E, et al. editors Biological psychiatry today. Elsevier North-Holland; Amsterdam: 1979. p. 294-302
38. Wetterberg L. Clinical importance of melatonin. Progr Brain Res 1979;52:539-47
39. Mendlewicz J, Linkowski P, Branchey L, et al. Abnormal 24 hour pattern of melatonin secretion in depression. Lancet 1979;2:1362
40. Beck-Friis J, Hanssen T, Kjellman BF, et al. Serum melatonin and cortisol in human subjects after the administration of dexamethasone and propranolol. Psychopharmacol Bull 1979;19:646-8 (Pubitemid 14228111)
41. Beck-Friis J, Kjellman BF, Aperia B, et al. Serum melatonin in relation to clinical variables in patients with major depressive disorder and a hypothesis of low melatonin syndrome. Acta Psychiatr Scand 1985;71:319-30 (Pubitemid 15114468)
42. Beck-Friis J, von Rosen D, Kjellman BF, et al. Melatonin in relation to body measures, sex, age, season and the use of drugs in patients with major affective disorders and healthy subjects. Psychoneuroendocrinology 1984;9:261-77 (Pubitemid 14071060)
43. Carrol BJ. The dexamethasone suppression test for melancholia. Br J Psychiatry 1982;140:292-304
44. Nair NP, Hariharasubramanian N, Pilapil C, et al. Circadian rhythm of plasma melatonin in endogenous depression. Prog Neuropsychopharmacol Biol Psychiatry 1984;8:715-18 (Pubitemid 15193233)
45. Wehr TA, Sack DA, Duncan WC, et al. Sleep and circadian rhythms in affective patients isolated from external time cues. Psychiatry Res 1985;15:327-39 (Pubitemid 15015251)
46. Tuunainen A, Kripke DF, Elliott JA, et al. Depression and endogenous melatonin in postmenopausal women. J Affect Disord 2002;69:149-58 (Pubitemid 34722880)
47. Sekula LK, Lucke JF, Heist EK, et al. Neuroendocrine aspects of primary endogenous depression. XV: mathematical modeling of nocturnal melatonin secretion in major depressives and normal controls. Psychiatry Res 1997;69:143-53 (Pubitemid 27146347)
48. Golden RN, Markey SP, Risby ED, et al. Antidepressants reduce whole-body norepinephrine turnover while enhancing 6-hydroxymelatonin out put. Arch Gen Psychiatry 1988;45:150-4 (Pubitemid 18052846)
49. Srinivasan V, Smits M, Spence W, et al. Melatonin mood disorders. World J Psychiatry 2006;7:138-51
50. Arendt J. Melatonin: a new probe in psychiatric investigation? Br J Psychiatry 1989;155:585-90 (Pubitemid 19269063)
51. Rubin RT, Heist EK, McGeoy SS, et al. Neuroendocrine aspects of primary endogenous depression. XI Serum melatonin measures in patients and matched control subjects. Arch Gen Psychiatry 1992;558-67
52. Shafii M, MacMillan DR, Key MP, et al. Case Study: melatonin in severe obesity. J Am Acad Child Adoles Psychiatry 1997;36:412-16 (Pubitemid 27098883)
53. Crasson M, Kjiri S, Colin A, et al. Serum melatonin and urinary 6-sulfatoxy-melatonin in major depression. Psychoneuroendocrinology 2004;29:1-12 (Pubitemid 37298011)
54. Thompson C, Mezey G, Corn T, et al. The effect of desipramine upon melatonin and cortisol secretion in depressed and normal subjects. Br J Psychiatry 1985;147:389-93 (Pubitemid 16237752)
55. Venkobarao A, Parvathi Devi S, Srinivasan V. Urinary melatonin in depression. Ind J Psychiatry 1983;25:167-72
56. Sack RL, Lewy AJ. Desmethylimipramine treatment increases melatonin production in humans. Biol Psychiatry 1986;21:406-10 (Pubitemid 16042962)
57. Bunney WE Jr, Murphy DL, Goodwin FK, et al. The Switch process from depression to mania. Relationship to drugs which alter brain monoamines. Lancet 1970;1:1022-7
58. Sitaram N, Gillin JC, Bunney WE Jr. The Switch process in manic-depressive illness. Circadian variations in time of switch and sleep and manic ratings before and after switch. Acta psychiatr Scand 1978;58:267-78 (Pubitemid 9002784)
59. Wehr TA, Goodwin FK. Tricycles modulate frequency of mood cycles. Chronobiologia 1979;6:377-85 (Pubitemid 10099455)
60. Souetre E, Salvati E, Belugou JL, et al. Circadian rhythms in depression and recovery: evidence for blunted amplitude in the main chronobiological abnormality. Psychiatry Res 1989;28:263-78 (Pubitemid 19165767)
61. Kennedy SH, Tighe S, McVey G, et al. Melatonin and Cortisol "switches" during mania, depression and euthymia in a drug free bipolar patient. J Nerv Ment Dis 1989;177:300-3 (Pubitemid 19130569)
62. Kennedy SH, Kutcher SP, Ralevski E, et al. Nocturnal melatonin and 24 hr 6-sulfatoxymelatonin levels in various phases of bipolar disorder. Psychiatry Res 1996;63:219-22 (Pubitemid 26276613)
63. Lewy AJ, Wehr T, Gold PW, et al. Plasma melatonin in manic depressive illness. In:. Kopin. Barchas Usdin EIJJD. editors Catecholamines: basic and clinical frontiers. Volume 2 Pergamon Press; Oxford: 1979. p. 1173-5
64. Nurnberger JI Jr, Adkins S, Lahiri DK, et al. Melatonin suppression by light in euthymic bipolar and unipolar patients. Arch Gen Psychiatry 2000;57:572-9 (Pubitemid 30349437)
65. Lewy AJ, Sack RL, Singer CM, et al. Winter Depression and phase shift hypothesis for bright light's therapeutic effects: history, theory and experimental evidence. J Biol Rhythms 1988;3:121-34
66. Danilenko KV, Putilov AA, Russkikh GS, et al. Diurnal and seasonal variations of melatonin and serotonin in women with seasonal affective disorder. Arctic Med Res 1994;53:137-45
67. Wehr TA, Duncan WC Jr, Sher L, et al. A circadian signal of change of season in patients with seasonal affective disorders. Arch Gen Psychiatry 2001;58:1108-14 (Pubitemid 33121501)
68. Touitou Y, Fevre M, Bogden A, et al. Patterns of plasma melatonin with ageing and mental condition: stability of nyctohemeral rhythms and differences in seasonal variations. Acta Endocrinol (Copenh) 1984;106:145-51 (Pubitemid 14107029)
69. Kivela A, Kauppila A, Ylostalo O, et al. Seasonal, menstrual and circadian secretions of melatonin, gonadotrophins and prolactin in women. Acta Physiol Scand 1988;132:321-7
70. Honma K, Honma S, Kohsaka M, et al. Seasonal variation in the human circadian rhythm: dissociation between sleep and temperature rhythms. Am J Physiol 1992;262:R885-91
71. Morera AL, Abreu P. Seasonality of psychopathology and circannual melatonin rhythms. J Pineal Res 2006;41:279-83 (Pubitemid 44337725)
72. Lewy AJ, Bauer VK, Cutler NL, et al. Morning vs evening light treatment of patients with winter depression. Arch Gen Psychiatry 1988;55:890-6
73. Terman JS, Terman JS. Light therapy for seasonal and non seasonal depression: protocol, safety and side effects. CNS Spectr 2005;10:647-63 (Pubitemid 41232548)
74. Ruhe HG, Mason NS, Schene AH. Mood is indirectly related to serotonin, norepinephrine and dopamine levels in humans: a meta-analysis of monoamine depletion studies. Mol Psychiatry 2007;12:331-59 (Pubitemid 46496835)
75. Rakofsky JJ, Holtzheimer PE, Nemeroff CB. Emerging targets for antidepressant therapies. Curr Opin Chem Biol 2009;13:291-302
76. Pandi-Perumal SR, Trakht I, Srinivasan V, et al. The effect of melatonergic and non-melatonergic antidepressants on sleep: weighing the alternatives. World J Biol Psychiatry 2008;4:1-13
77. Thase ME. Pharmacotherapy of bipolar depression: an update. Curr Psychiatry Rep 2006;8:478-88 (Pubitemid 46017238)
78. Winokur A, Gary KA, Rodner S, et al. Depression, sleep physiology and antidepressant drugs. Depress Anxiety 2001;14:19-28 (Pubitemid 32801613)
79. De Martinis NA, Winokur A. Effects of psychiatric medications on sleep and sleep disorders. CNS Neurol Disord Drug Targets 2007;6:17-29 (Pubitemid 46322292)
80. Racagni G, Riva MA, Molteni R, et al. Mode of action of agomelatine: synergy between melatonergic and 5-HT2c receptors. World J Biol Psychiatry 2011;12:574-87
81. Nasrallah HA, Targum SD, Tandon R, et al. Defining and measuring clinical effective-ness in the treatment of schizophrenia. Psychiatry Serv 2005;56(3):273-82 (Pubitemid 40333559)
82. Kennedy SH, Young AH, Blier P. Strategies to achieve clinical effectiveness: refining existent therapies and pursuing emerging targets. J Affect Disord 2011
83. Demyttenaere K. Agomelatine: a narrative review. Eur Neuropsychopharmacol 2011;21:S703-9
84. Serna MC, Cruz I, Real J, et al. Duration and adherence of antidepressant treatment. (2003 to 2007) based on prescription database. Eur Psychiatry 2010;25(4):206-13
85. Sheehan DV, Keene MS, Eaddy M, et al. Differences in medication adherence and health care resource utilization patterns: older versus newer antidepressants agents in patients with depression and/or anxiety disorders. CNS Drugs 2008;22(11):963-73
86. Millan MJ, Gobert A, Lejeune F, et al. The novel melatonin agonist (S20098) is an antagonist at 5-hydroxytryptamine 2C receptors, blockade of which enhances the activity of fronocortical dopaminergic and adrenergic pathways. J Pharmacol Exp Ther 2003;306:954-64 (Pubitemid 37025301)
87. Bourin M, Mocaer E, Porsolt R. Antidepressant like activity of S 20098 (agomelatine) in the forced swimming test in rodents.: involvement of melatonin and serotonin receptors. J Psychiatry Neurosci 2004;29:126-33 (Pubitemid 38570217)
88. Fuchs E. Social stress in tree shrews as an animal model of depression: an example of behavioural model of CNS disorder. CNS Spectr 2005;10:182-90 (Pubitemid 40489287)
89. Pepin MC, Pothier F, Barden N. Antidepressant drug action in a transgenic mouse model of endocrine changes seen in depression. Mol Pharmacol 1992;42:991-5 (Pubitemid 23028833)
90. Barden N, Shink E, Labbe M, et al. Antidepressant action of agomelatine (S20098) in a transgenic mouse model. Prog Neuropsychopharmacol Biol Psychiatry 2005;29:908-16
91. Papp M, Gruca B, Boyer PA, et al. Effect of agomelatine in the chronic mild stress model of depression. Neuropsychopharmacology 2003;28:694-703
92. Redman JR, Guardiola-Lemaitre B, Brown M, et al. Dose dependent effects of S-20098, a melatonin agonist on a direction of re-entrainment of rat circadian activity rhythms. Psychopharmacol (Berlin) 1995;118:385-90
93. Armstrong SM, McNulty OM, Guardiola-Lemaitre B, et al. Successful use of S-20098 and melatonin in an animal model of delayed-sleep phase syndrome (DSPS). Pharmacol Biochem Behav 1993;46:45-9
94. Martinet L, Guardiola-Lemaitre B, Mocaer E. Entrainment of circadian rhythms by S-20098, a melatonin agonist is dose and plasma concentration. Dependent. Pharmacol Biochem Behav 1996;54:713-18 (Pubitemid 26258654)
95. Redman JR, Francis AJ. Entrainment of rat circadian rhythms by melatonin antagonist S-20098 requires the intact suprachiasmatic nucleus but not pineal. J Biol Rhythms 1998;13:39-51 (Pubitemid 128478945)
96. Pitrosky B, Kirsch R, Malan A, et al. Organization of rat circadian rhythms during daily infusion of melatonin or S 20098, a melatonin agonist. Am J Physiol 1999;277(3 Pt 2):R812-28 (Pubitemid 29458154)
97. Weibel L, Turek FW, Mocaer E, et al. A melatonin agonist facilitates circadian resynchronization in old hamsters after abrupt shifts in the light-dark cycle. Brain Res 2000;880(1-2):207-11
98. Rainer Q, Xia L, Guilloux JP, et al. Beneficial behavioural and neurogenic effects of agomelatine in a model of depression/anxiety. Int J Neuropsychopharmacol 2011;doi:10.1017/S1461145711000356
99. Paizanis E, Renoir T, Lelievre V, et al. Behavioural and neuroplastic effects of the new-generation antidepressant agomelatine compared to fluoxetine in glucocorticoid receptor-impaired mice. Int J Neuropsychopharmacol 2010;13:759-74
100. Bansar M, Soumier A, Hery M, et al. Agomelatine, a new antidepressant, induces regional changes in hippocampal neurogenesis. Biol Psychiatry 2006;59:1087-96 (Pubitemid 43849657)
101. Soumier A, Bansar M, Lortet S, et al. Mechanisms contributing to the phase-dependent regulation of neurogenesis by the novel antidepressant agomelatine, in the adult rat hippocampus. Neuropsychopharmacology 2009;34:2390-403
102. Bannerman DM, Deacon RM, Brady S, et al. A comparison of GluR-A deficient and Wild type mice on a test battery assessing sensorimotor, affective and cognitive behaviours. Behav Neurosci 2004;118:643-7 (Pubitemid 38685333)
103. Fanselow MS, Dong HW. Are the dorsal and ventral hippocampus functionally distinct structures?. Neuron 2010;65:7-19
104. Alves SH, Pinheiro G, Motta A, et al. Anxiogenic effects in the rat elevated plus-maze of 5-HT(2C) agonists into ventral but not dorsal hippocampus. Behav Pharmacol 2004;15:37-43 (Pubitemid 38241512)
105. Papp M, Gruca P, Boyer P, et al. Effect of agomelatine in the chronic mild stress model of depression in the rat. Neuropsychopharmacology 2003;28:604-703
106. San L, Arranz B. A novel mechanism of antidepressant action involving melatonergic serotonergic system. Eur Psychiatry 2008;23:396-402
107. 1 melatonin receptor expression in the suprachiasmatic nucleus of the C3H/HeN mouse. J Pineal Res 2000;28:185-92 (Pubitemid 30162451)
108. Millan MJ, Gobert A, Rivet JM, et al. Mirtazapine enhances frontocortical dopaminergic and cortico limbic adrenergic but not serotonergic transmission by blockade of alpha-2 adrenergic and serotonergic 2c receptors; a comparison with citalopram. Eur J Neurosci 2000;12:1079-95 (Pubitemid 30168787)
109. Mairesse J, Silletti V, Laloux C, et al. Chronic agomelatine treatment corrects the abnormalities in the circadian rhythm of motor activity and sleep/wake cycle induced by prenatal restraint stress in adult rats. Int J Neuropsychopharmacol 2012;6:1-16
110. Racagni G, Riva MA, Popoli M. The interactions between the internal clock and antidepressant efficacy. Int Clin Psychopharmacol 2007;22(Suppl 2):S9-S14 (Pubitemid 47530848)
111. Martin JR, Bos M, Jenck F, et al. 5-HT2c receptor agonists: pharmacological characteristics and therapeutic potential. J Pharmacol Exp Ther 1998;286:913-24 (Pubitemid 29003485)
112. Fuchs E, Simon M, Schmelting Pharmacology of a new antidepressant; benefits of the implications of the melatonergic system. Int J Clin Psychopharmacol 2006(Suppl 1):S17-20 (Pubitemid 43740328)
113. Krauchi K, Cajochen C, Mori D, et al. Early evening melatonin and S 20098 advance circadian phase and nocturnal regulation of core body temperature. Am J Physiol 1997;272:R1178-88
114. Leproult R, Van Onderbergen A, L'Hermite-Balerlaux M, et al. Phase shifts of 24-h rhythms of hormonal release and body temperature following early evening administration of the melatonin agonist agomelatine in healthy old men. Clin Endocrinol 2005;63:296-304
115. Eser D, Baghai TC, Moller HJ. Agomelatine: the evidence for its place in the treatment of depression. Core Evid 2009;3:171-9
116. Loo H, Hale A, D'haenen H. Determination of the dose of agomelatine, a melatonergic agonist and selective 5-HT(2C) antagonist in the treatment of major depressive disorder. Int Clin Psychopharmacol 2002;17:239-47
117. Kennedy SH, Emsley RA. Placebo-controlled trial of agomelatine in the treatment of major depressive disorder. Eur Neuropsychopharmacol 2006;16(2):93-100 (Pubitemid 43145814)
118. Olie JP, Kasper S. Efficacy of agomelatine, a MT1/MT2 receptor agonist with 5-HT2c antagonistic properties in major depressive disorder. Int J Neuropsychol Pharmacol 2007;10(5):661-73 (Pubitemid 47517525)
119. Lemoine R, Guilleminault C, Alvarez E. Improvement in subjective sleep in major depressive disorder with a novel antidepressant agomelatine: randomized, double-blind comparison with venlafaxine. J Clin Psychiatry 2007;68:1723-32 (Pubitemid 350247502)
120. Pjrek E, Winkler D, Konstantinidis A, et al. Agomelatine in the treatment of seasonal affective disorder. Psychopharmacology (Berl) 2007;190:575-9 (Pubitemid 46204474)
121. Kennedy SH, Rizvi S, Fulton K, et al. A double blind comparison of sexual functioning, antidepressant efficacy, and tolerability between agomelatine and venlafaxine XR. J Clin Psychopharmacol 2008;28(3):329-33
122. Calabrese JR, Guelfi JD, Perdrizet-Chevallier C. Agomelatine Bipolar study group. Agomelatine adjunctive therapy for acute bipolar depression: preliminary open data. Bipolar Disord 2007;6:628-35 (Pubitemid 47365631)
123. Goodwin GM, Emsley R, Rembry S, et al. Agomelatine prevents relapse in patients with major depressive disorder without evidence of a discontinuation syndrome: a 24-week randomized, double-blind, placebo controlled trial. J Clin Psychiatry 2009;70(8):1128-37
124. Zajecka J, Schatzberg A, Stahl et al. Efficacy and safety of agomelatine in treatment of major depressive disorder: a multicenter, randomized, double-blind, placebo controlled trial. J Clin Psychopharmacol 2010;30(2):135-44
125. Stahl SM, Fava M, Trivedi MH, et al. Agomelatine in the treatment of major depressive disorder: an 8 week, multicenter, randomized, placebo controlled trial. J Clin Psychiatry 2010;71(5):616-26
126. Hale A, Corral RM, Mencacci C, et al. Superior antidepressant efficacy results of agomelatine versus fluoxetine in severe MDD patients: a randomized double-blind study. Int Clin Psychopharmacol 2010;25(6):305-14
127. Kasper S, Hajak G, Wulff K, et al. Efficacy of the novel antidepressant agomelatine on the circadian rest-activity cycle and depressive and anxiety symptoms in patients with major depressive disorder: a randomized, double blind comparison with sertraline. J Clin Psychiatry 2010;71(2):109-20
128. Di Giannantonio M, Di Iorio G, Guglielmo R, et al. Major depressive disorder, anhedonia and agomelatine: an open-label study. J Biol Regul Homeost Agents 2011;25(1):109-14
129. De Beradis D, Serroni N, Campanella D, et al. A case of Obsessive-compulsive disorder successfully treated with agomelatine monotherapy. J Clin Psychopharmacol 2012;32(2):289-90
130. Montgomery SA, Kasper S. Severe depression and antidepressants: focus on a pooled analysis of placebo-controlled studies on agomelatine. Int Clin Psychoharmacol 2007;22:283-91 (Pubitemid 47237547)
131. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960;23:56-62
132. Montgomery SA, Ashberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry 1979;134:382-9 (Pubitemid 9136500)
133. Rouillon F. Efficacy and tolerance profile of agomelatine and practical use in depressed patients. Int Clin Psychopharmacol 2006;21(Suppl 1):531-5
134. Kennedy SH, Rizvi SJ. Agomelatine in the treatment of major depressive disorder: potential for clinical effectiveness. CNS Drugs 2010;24(6):479-99
135. Montgomery SA, Kennedy SH, Burrows GD, et al. Absence of discontinuation symptoms with agomelatine and occurrence of discontinuation with paroxetine. A randomized double-blind placebo controlled discontinuation study. Int Clin Psychopharmacol 2004;19:271-80 (Pubitemid 39141943)
136. Pandi-Perumal SR, Srinivasan V, Cardinali DP, et al. Could agomelatine be the ideal antidepressant?. Expert Rev Neurother 2006;6:1595-608 (Pubitemid 44904007)
137. Fornaro M, Prestia D, Colicchio S, et al. A systematic, updated review on the antidepressant agomelatine focusing on its melatonergic modulation. Curr Neuropharmacol 2010;8:287-304
138. De Beradis D, Di Lorio G, Acciavatti T, et al. The emerging role of melatonin agonists in the treatment of major depression: focus on agomelatine. CNS Neurol Disord Drug Targets 2011;10(1):119-32
139. Quera-Salva MA, Hajak G, Montplaisir J, et al. Comparison of agomelatine and escitalopram on night time sleep and daytime condition and efficiency in major depressive disorder patients. Int Clin Psychopharmacol 2011;26:252-62
140. Stein Ahokas AA, deBodinat C. Efficacy of agomelatine in generalized anxiety disorder.: a randomized double-blind placebo controlled study. J Clin Psychopharmacol 2008;28:561-6
141. Crippa JAS, Hallak JEC, Zuardi AW, et al. Agomelatine in the treatment of social anxiety disorder. Prog Neuropsychopharmacol Biol Psychiatry 2010;34:1357-8
142. Lam RW. Sleep disturbances and depression: a challenge for antidepressants. Int Clin Psychopharmacol 2006;21(Suppl 1):S25-9 (Pubitemid 43740330)
143. Montgomery SA, Kasper S. Severe depression and antidepressants: focus on a pooled analysis of placebo-controlled studies on agomelatine. Int Clin Psychopharmacol 2007;22:283-91 (Pubitemid 47237547)
144. Green B. Focus on agomelatine. Curr Med Res Opin 2011;27(4):745-9
145. Bertaina-Anglade V, La Rochelle CD, Boyer PA, et al. Antidepressant like effects of agomelatine (S 20098) in the learned helplessness model. Behav Pharmacol 2006;17:703-13