A. Gilles, B. Pharmacie-clinique-alain, B. Jean-claude, C. Santé-publique-christine, F. Pharmacologie-cardiovasculaire-chantal et al., Chimie physique générale, Biologie cellulaire oncologique Jean-Bernard REGNOUF de VAINS ........ Chimie thérapeutique Bertrand RIHN .................................. Biochimie, Biologie

A. Monique, V. Bactériologie, B. Sandrine, B. Mariette, B. Biologie-cellulaire-emmanuelle et al., Chimie thérapeutique François BONNEAUX Chimie thérapeutique

H. Thierry, J. Chimie-organique-frédéric, . Santé, J. Olivier, . Toxicologie et al., Biophysique, Informatique Christine PERDICAKIS ........................ Chimie

S. Anne, S. Pharmacie-galénique-marie-paule, B. Mycologie, T. Nathalie, T. Santé-publique-gabriel et al., Biological rythm in psychiatry, Biochimie et Biologie moléculaire Colette ZINUTTI ................................ Eur Psychiatry, vol.20, pp.99-154, 2005.

J. Alonso, M. Angermeyer, S. Bernert, R. Bruffaerts, T. Brugha et al., 12-Month comorbidity patterns and associated factors in Europe : results from the European Study of the Epidemiology of Mental Disorders (ESEMeD) project, Acta Psychiatr Scand, vol.109, pp.28-37, 2004.

P. Andlin-sobicki and H. Wittchen, Cost of affective disorders in Europe, European Journal of Neurology, vol.21, issue.s1, pp.34-38, 2005.
DOI : 10.1192/bjp.184.5.386

J. Arendt, . Melatonin, and . Human, Melatonin and Human Rhythms, Chronobiology International, vol.341, issue.1, pp.21-37, 2006.
DOI : 10.1016/S0304-3940(03)00122-8

URL : http://rcin.org.pl/Content/29017

V. Audinot, F. Mailliet, and B. Lahaye, New selective ligands of human cloned melatonin MT1 and MT2 receptors, Naunyn-Schmiedeberg's Archives of Pharmacology, vol.367, issue.6, pp.553-561, 2003.
DOI : 10.1007/s00210-003-0751-2

M. Banasr, A. Soumier, M. Hery, E. Mocaër, and A. Daszuta, Agomelatine, a New Antidepressant, Induces Regional Changes in Hippocampal Neurogenesis, Biological Psychiatry, vol.59, issue.11, pp.1087-1096, 2006.
DOI : 10.1016/j.biopsych.2005.11.025

URL : https://hal.archives-ouvertes.fr/hal-00087540

D. Bannerman, J. Rawlins, S. Mchugh, R. Deacon, B. Yee et al., Regional dissociations within the hippocampus???memory and anxiety, Neuroscience & Biobehavioral Reviews, vol.28, issue.3, pp.273-283, 2004.
DOI : 10.1016/j.neubiorev.2004.03.004

N. Barden, Regulation of corticosteroid receptor gene expression in depression and antidepressant action, J Psychiatry Neurosci, vol.24, pp.25-39, 1999.

N. Barden, E. Shink, M. Labbé, R. Vacher, J. Rochford et al., Antidepressant action of agomelatine (S 20098) in a transgenic mouse model, Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol.29, issue.6, pp.908-916, 2005.
DOI : 10.1016/j.pnpbp.2005.04.032

P. Barrett, S. Conway, and P. Morgan, Digging deep - structure-function relationships in the melatonin receptor family, Journal of Pineal Research, vol.62, issue.4, pp.221-251, 2003.
DOI : 10.1095/biolreprod62.4.1096

V. Bertaina-anglade, L. Rochelle, C. Boyer, P. Mocaer, and E. , Antidepressant-like effects of agomelatine (S 20098) in the learned helplessness model, Behavioural Pharmacology, vol.17, issue.8, pp.703-713, 2006.
DOI : 10.1097/FBP.0b013e3280116e5c

J. Bogaards, E. Hissink, and M. Briggs, Prediction of interindividual variation in drug plasma levels in vivo from individual enzyme kinetic data and physiologically based pharmacokinetic modeling, European Journal of Pharmaceutical Sciences, vol.12, issue.2, pp.117-141, 2000.
DOI : 10.1016/S0928-0987(00)00146-9

T. Bougerol and S. Dépressif, orientation diagnostique et principes du traitement, La revue du praticien, vol.49, issue.6, pp.643-652, 1999.

M. Bourin, E. Mocaër, and R. Porsolt, Antidepressant-like activity of S 20098 (agomelatine) in the forced swimming test in rodents: involvement of melatonin and serotonin receptors, J Psychiatry Neurosci, vol.29, pp.126-133, 2004.

M. Bouvard and J. Cottraux, Protocoles et échelles d'évaluation en psychiatrie et en psychologie, 2002.

N. Buscemi, B. Vandermeer, N. Hooton, R. Pandya, L. Tjosvold et al., Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis, BMJ, vol.332, issue.7538, pp.385-93, 2006.
DOI : 10.1136/bmj.38731.532766.F6

D. Buysse, E. Frank, K. Lowe, C. Cherry, and D. Kupfer, Electroencephalographic sleep correlates of episode and vulnerability to recurrence in depression, Biological Psychiatry, vol.41, issue.4, pp.406-424, 1997.
DOI : 10.1016/S0006-3223(96)00041-8

C. Cajochen, K. Krauchi, and A. Wirz-justice, Role of Melatonin in the Regulation of Human Circadian Rhythms and Sleep, Journal of Neuroendocrinology, vol.505, issue.Suppl. 1, pp.432-437, 2003.
DOI : 10.1111/j.1469-7793.1997.851ba.x

D. Cardinali, D. Golombek, R. Rosenstein, R. Cutrera, and A. Esquifin, Melatonin site and mechanism of action: Single or multiple?, Journal of Pineal Research, vol.21, issue.1, pp.32-39, 1997.
DOI : 10.1016/0014-5793(88)80411-3

D. Cardinali, S. Pandi-perumal, V. Srinivasan, D. Spence, and I. Trakht, Therapeutic potential of melatonin agonists, Expert Review of Endocrinology & Metabolism, vol.19, issue.2, pp.269-279, 2008.
DOI : 10.1097/01.yic.0000137184.64610.c8

N. Cermakian and P. Sassone-corsi, The molecular mechanisms of the circadian clock

N. Cermakian and D. Boivin, A molecular perspective of human circadian rhythm disorders, Brain Research Reviews, vol.42, issue.3, pp.204-220, 2003.
DOI : 10.1016/S0165-0173(03)00171-1

S. Chellappa, C. Schroder, and C. Cajochen, Chronobiology, excessive daytime sleepiness and depression: Is there a link?, Sleep Medicine, vol.10, issue.5, pp.10-16, 2008.
DOI : 10.1016/j.sleep.2008.05.010

B. Claustrat, J. Brun, and G. Chazot, M??latonine, rythme veille-sommeil et sommeil, M??decine du Sommeil, vol.1, issue.4, pp.11-19, 2005.
DOI : 10.1016/S1769-4493(05)70144-8

B. Claustrat, J. Brun, and G. Chazot, The basic physiology and pathophysiology of melatonin, Sleep Medicine Reviews, vol.9, issue.1, pp.11-24, 2005.
DOI : 10.1016/j.smrv.2004.08.001

A. Clayton, J. Pradko, and H. Croft, Prevalence of Sexual Dysfunction Among Newer Antidepressants, The Journal of Clinical Psychiatry, vol.63, issue.4, pp.357-366, 2002.
DOI : 10.4088/JCP.v63n0414

S. Conway, S. Canning, H. Howell, E. Mowat, P. Barrett et al., Characterisation of human melatonin mt1 and MT2 receptors by CRE-luciferase reporter assay, European Journal of Pharmacology, vol.390, issue.1-2, pp.15-24, 2000.
DOI : 10.1016/S0014-2999(99)00914-0

E. Corruble, D??pression r??currente et ??v??nements de vie : de la clinique ?? de nouveaux mod??les explicatifs ? Enqu??te ACTUEL, L'Enc??phale, vol.32, issue.6, pp.983-987, 2006.
DOI : 10.1016/S0013-7006(06)76277-7

M. Crasson, S. Kjiri, and C. A. , Serum melatonin and urinary 6-sulfatoxymelatonin in major depression, Psychoneuroendocrinology, vol.29, issue.1, pp.1-12, 2004.
DOI : 10.1016/S0306-4530(02)00123-3

E. Dalton, D. Rotondi, R. Levitan, S. Kennedy, and G. Brown, Use of slow-release melatonin in treatment-resistant depression, J Psychiatry Neurosci, vol.25, issue.1, pp.48-52, 2000.

H. Dardente, P. Klosen, P. Pévet, and M. Masson-pévet, MT1 Melatonin Receptor mRNA Expressing Cells in the Pars Tuberalis of the European Hamster: Effect of Photoperiod, Journal of Neuroendocrinology, vol.15, issue.8, pp.778-786, 2003.
DOI : 10.1016/S0940-9602(11)80177-9

P. Delagrange, J. Atkinson, J. Boutin, L. Casteilla, D. Lesieur et al., Therapeutic Perspectives for Melatonin Agonists and Antagonists, Journal of Neuroendocrinology, vol.58, issue.4, pp.442-448, 2003.
DOI : 10.1136/oem.58.11.747

URL : https://hal.archives-ouvertes.fr/hal-00409043

P. Devoto, G. Flore, L. Pira, G. Longu, and G. Gessa, Alpha2-adrenoceptor mediated co-release of dopamine and noradrenaline from noradrenergic neurons in the cerebral cortex, Journal of Neurochemistry, vol.148, issue.4, pp.1003-1009, 2004.
DOI : 10.1111/j.1471-4159.1993.tb02168.x

D. Dijk, V. Schantz, and M. , Timing and Consolidation of Human Sleep, Wakefulness, and Performance by a Symphony of Oscillators, Journal of Biological Rhythms, vol.277, issue.4, pp.279-290, 2005.
DOI : 10.1113/jphysiol.2004.061606

M. Dubocovich, Melatonin receptors: Are there multiple subtypes?, Trends in Pharmacological Sciences, vol.16, issue.2, pp.50-56, 1995.
DOI : 10.1016/S0165-6147(00)88978-6

M. Dubocovich and M. Markowska, Functional MT1 and MT2 melatonin receptors in mammals, Endocrine, vol.2, pp.101-110, 2005.

M. Dubocovich, D. Cardinali, and P. Delagrange, The IUPHAR compendium of receptor characterization and classification, IUPHAR Media, 2000.

R. Duman, Role of Neurotrophic Factors in the Etiology and Treatment of Mood Disorders, NeuroMolecular Medicine, vol.5, issue.1, pp.11-25, 2004.
DOI : 10.1385/NMM:5:1:011

W. Duncan, Circadian rhythms and the pharmacology of affective illness, Pharmacology & Therapeutics, vol.71, issue.3, pp.253-312, 1996.
DOI : 10.1016/S0163-7258(96)00092-7

J. Dunlap, Molecular Bases for Circadian Clocks, Cell, vol.96, issue.2, pp.271-290, 1999.
DOI : 10.1016/S0092-8674(00)80566-8

A. Eisch, Adult neurogenesis: implications for psychiatry, Prog Brain Res, vol.138, pp.315-342, 2002.
DOI : 10.1016/S0079-6123(02)38085-3

E. Medicines-agency and E. , Questions et réponses sur la recommandation de refus de l'autorisation de mise sur le marché pour VALDOXAN/THYMANAX, Réf. Doc. EMEA, vol.16, issue.01, 2006.

J. Ferguson, R. Shrivastava, S. Stahl, J. Hartford, F. Borian et al., Reemergence of Sexual Dysfunction in Patients With Major Depressive Disorder, The Journal of Clinical Psychiatry, vol.62, issue.1, pp.24-29, 2001.
DOI : 10.4088/JCP.v62n0106

G. Glickman, B. Byrne, C. Pineda, W. Hauck, and G. Brainard, Light Therapy for Seasonal Affective Disorder with Blue Narrow-Band Light-Emitting Diodes (LEDs), Biological Psychiatry, vol.59, issue.6, pp.502-507, 2006.
DOI : 10.1016/j.biopsych.2005.07.006

G. Goodwin, F. Rouillon, and R. Emsley, P.2.c.038 Long-term efficacy of agomelatine, a novel antidepressant, in the prevention of relapse in out-patients with major depressive disorder, European Neuropsychopharmacology, vol.17, issue.4, p.361, 2007.
DOI : 10.1016/S0924-977X(07)70529-1

URL : https://hal.archives-ouvertes.fr/hal-00820755

G. Lemaitre and B. , Agonistes et antagonistes des r??cepteurs m??latoninergiques : effets pharmacologiques et perspectives th??rapeutiques, Annales Pharmaceutiques Fran??aises, vol.63, issue.6, pp.385-400, 2005.
DOI : 10.1016/S0003-4509(05)82308-9

C. Guilleminault, Efficacy of agomelatine versus venlafaxine on subjective sleep of patients with major depressive disorder, Eur Psychopharmacol, vol.15, issue.3, pp.419-439, 2005.

C. Guilleminault, How the internal clock interacts with mood and depression, European Psychiatry, vol.22, pp.89-95, 2007.
DOI : 10.1016/j.eurpsy.2007.01.1175

P. Hamet and J. Tremblay, Genetics of the sleep-wake cycle and its disorders, Metabolism, vol.55, issue.55, pp.7-12, 2006.
DOI : 10.1016/j.metabol.2006.07.006

M. Hamon and S. Bourgoin, Pharmacological profile of antidepressants: a likely basis for their efficacy and side effects?, European Neuropsychopharmacology, vol.16, pp.625-632, 2006.
DOI : 10.1016/S0924-977X(06)70008-6

M. Hamon, E. Mocaer, and P. Boyer, Pathophysiology and treatment of affective disorders: melatonin and serotonin, Medicographia, vol.27, issue.3, pp.228-235, 2005.

N. Hanoun, E. Mocaer, P. Boyer, M. Hamon, and L. Lanfumey, Differential effects of the novel antidepressant agomelatine (S 20098) versus fluoxetine on 5-HT1A receptors in the rat brain, Neuropharmacology, vol.47, issue.4, pp.515-526, 2004.
DOI : 10.1016/j.neuropharm.2004.06.003

F. Jenck, J. Moreau, V. Mutel, J. Martin, and W. Haefely, Evidence for a role of 5-HT1C receptors in the antiserotonergic properties of some antidepressant drugs, European Journal of Pharmacology, vol.231, issue.2, pp.223-229, 1993.
DOI : 10.1016/0014-2999(93)90453-O

R. Jindal and M. Thase, Treatment of insomnia associated with clinical depression, Sleep Medicine Reviews, vol.8, issue.1, pp.19-30, 2004.
DOI : 10.1016/S1087-0792(03)00025-X

J. Johnston, B. Tournier, H. Andersson, M. Masson-pevet, and G. Lincoln, Multiple Effects of Melatonin on Rhythmic Clock Gene Expression in the Mammalian Pars Tuberalis, Endocrinology, vol.147, issue.2, pp.959-965, 2006.
DOI : 10.1210/en.2005-1100

URL : https://hal.archives-ouvertes.fr/hal-00093434

R. Judge, M. Parry, D. Quail, and J. Jacobson, Discontinuation symptoms: comparison of brief interruption in fluoxetine and paroxetine treatment, International Clinical Psychopharmacology, vol.17, issue.5, pp.217-225, 2002.
DOI : 10.1097/00004850-200209000-00002

A. Karakas and B. Gündüz, ), Chronobiology International, vol.141, issue.1-2, pp.225-261, 2006.
DOI : 10.2337/diab.45.10.1435

M. Karolczak, H. Korf, and J. Stehle, The Rhythm and Blues of Gene Expression in the Rodent Pineal Gland, Endocrine, vol.27, issue.2, pp.89-100, 2005.
DOI : 10.1385/ENDO:27:2:089

S. Kasper, L. Laigle, and F. Bayle, P.2.c.022 Superior antidepressant efficacy of agomelatine versus sertraline: a randomised, double-blind study, European Neuropsychopharmacology, vol.18, pp.336-337, 2008.
DOI : 10.1016/S0924-977X(08)70468-1

URL : https://hal.archives-ouvertes.fr/in2p3-00293667

S. Kennedy and R. Emsley, Placebo-controlled trial of agomelatine in the treatment of major depressive disorder, European Neuropsychopharmacology, vol.16, issue.2, pp.93-100, 2006.
DOI : 10.1016/j.euroneuro.2005.09.002

S. Kennedy and C. Guilleminault, P.2.c.013 Antidepressant efficacy of agomelatine 25-50 mg versus venlafaxine 75 -150 mg: two randomized, double blind studies, European Neuropsychopharmacology, vol.16, issue.4, pp.319-320, 2006.
DOI : 10.1016/S0924-977X(06)70347-9

URL : https://hal.archives-ouvertes.fr/in2p3-00361601

S. Kennedy and B. Eisfeld, Agomelatine and its therapeutic potential in the depressed patient, Neuropsychiatric Disease and Treatment, vol.4, issue.3, pp.423-428, 2007.

G. Kennett, M. Wood, F. Bright, B. Trail, G. Riley et al., SB 242084, a Selective and Brain Penetrant 5-HT 2C Receptor Antagonist, Neuropharmacology, vol.36, issue.4-5, pp.609-620, 1997.
DOI : 10.1016/S0028-3908(97)00038-5

R. Kessler, G. Andrews, D. Mroczek, B. Ustun, and H. Wittchen, The World Health Organization Composite International Diagnostic Interview short-form (CIDI-SF), International Journal of Methods in Psychiatric Research, vol.28, issue.4, pp.171-185, 1998.
DOI : 10.1001/archpsyc.1994.03950010008002

R. Kessler, P. Berglund, O. Demler, J. R. Walters, and E. , Lifetime Prevalence and Age-of-Onset Distributions of DSM-IV Disorders in the National Comorbidity Survey Replication, Archives of General Psychiatry, vol.62, issue.6, pp.593-602, 2005.
DOI : 10.1001/archpsyc.62.6.593

A. Khan, S. Khan, G. Walens, R. Kolts, and E. Giller, Frequency of Positive Studies Among Fixed and Flexible Dose Antidepressant Clinical Trials: An Analysis of the Food and Drug Administraton Summary Basis of Approval Reports, Neuropsychopharmacology, vol.52, issue.3, pp.552-557, 2003.
DOI : 10.1097/00004850-199403001-00006

D. Klein and R. Moore, Pineal N-acetyltransferase and hydroxyindole-O-methyl-transferase: control by the retinohypothalamic tract and the suprachiasmatic nucleus, Brain Research, vol.174, issue.2, pp.245-62, 1979.
DOI : 10.1016/0006-8993(79)90848-5

M. Kodama, T. Fujioka, and R. Duman, Chronic olanzapine or fluoxetine administration increases cell proliferation in hippocampus and prefrontal cortex of adult rat, Biological Psychiatry, vol.56, issue.8, pp.570-580, 2004.
DOI : 10.1016/j.biopsych.2004.07.008

D. Kupfer, Depression and associated sleep disturbances: patient benefits with agomelatine, European Neuropsychopharmacology, vol.16, issue.5, pp.639-643, 2006.
DOI : 10.1016/S0924-977X(06)70010-4

D. Kupfer, D. Spiker, P. Coble, J. Neil, R. Ulrich et al., Sleep and treatment prediction in endogenous depression, Am J Psychiatry, vol.138, pp.429-434, 1981.

M. Lader, Limitations of current medical treatments for depression: Disturbed circadian rhythms as a possible therapeutic target, European Neuropsychopharmacology, vol.17, issue.12, pp.743-755, 2007.
DOI : 10.1016/j.euroneuro.2007.05.004

R. Lam, Sleep disturbances and depression: a challenge for antidepressants, International Clinical Psychopharmacology, vol.21, issue.Supplement 1, pp.25-29, 2006.
DOI : 10.1097/01.yic.0000195658.91524.61

R. Lam, S. Kennedy, S. Grigoriadis, R. Mcintyre, R. Milev et al., Canadian Network for Mood and Anxiety Treatments (CANMAT) Clinical guidelines for the management of major depressive disorder in adults., Journal of Affective Disorders, vol.117, pp.26-43, 2009.
DOI : 10.1016/j.jad.2009.06.041

R. Launois and S. Payet, Évaluation pharmacoéconomique des épisodes dépressifs majeurs et des récidives, Neuropsy News, vol.5, pp.221-229, 2003.

P. Lemoine, C. Guilleminault, and E. Alvarez, Improvement in Subjective Sleep in Major Depressive Disorder With a Novel Antidepressant, Agomelatine, The Journal of Clinical Psychiatry, vol.68, issue.11, pp.1723-1732, 2007.
DOI : 10.4088/JCP.v68n1112

R. Leproult, A. Van-onderbergen, L. 'hermite-baleriaux, M. , V. Cauter 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 older men, Clinical Endocrinology, vol.43, issue.3, pp.298-304, 2005.
DOI : 10.1016/0165-1781(95)02701-W

L. Strat, Y. Ramoz, N. Gorwood, and P. , Troubles de l???humeur et rythmes biologiques, Annales Pharmaceutiques Fran??aises, vol.66, issue.3, pp.169-174, 2008.
DOI : 10.1016/j.pharma.2008.04.005

H. Lett, J. Blumenthal, M. Babyak, S. A. Straumant, C. Robins et al., Depression as a risk factor for coronary artery disease: evidence, mechanisms, and treatment, Psychosom Med, vol.66, pp.305-315, 2004.

A. Lewy, S. Ahmed, L. Jackson, J. Sack, and R. , Melatonin shifts human circadian rhythms according to a phase-response curve, Chronobiol Int, vol.60, pp.105-117, 1994.

A. Lewy, B. Lefler, J. Emens, and V. Bauer, The circadian basis of winter depression, Proceedings of the National Academy of Sciences, vol.287, issue.14, pp.7414-7419, 2006.
DOI : 10.1001/jama.287.14.1840

C. Liu, C. Fukuhara, and J. Wessel, Localization of Aa-nat mRNA in the rat retina by fluorescence in situ hybridization and laser capture microdissection, Cell and Tissue Research, vol.315, issue.2, pp.197-201, 2004.
DOI : 10.1007/s00441-003-0822-1

H. Loo and A. Hale, Determination of the dose of agomelatine, a melatoninergic agonist and selective 5-HT2C antagonist, in the treatment of major depressive disorder: a placebo-controlled dose range study, Int Clin Psychopharmacol, vol.17, pp.239-247, 2002.

M. Lopes, M. Quera-salva, and C. Guilleminault, Non-REM sleep instability in patients with major depressive disorder: Subjective improvement and improvement of non-REM sleep instability with treatment (Agomelatine), Sleep Medicine, vol.9, issue.1, pp.33-41, 2007.
DOI : 10.1016/j.sleep.2007.01.011

M. Macchi and J. Bruce, Human pineal physiology and functional significance of melatonin, Frontiers in Neuroendocrinology, vol.25, issue.3-4, pp.177-195, 2004.
DOI : 10.1016/j.yfrne.2004.08.001

V. Maletic, M. Robinson, T. Oakes, S. Iyengar, S. Ball et al., Neurobiology of depression: an integrated view of key findings, International Journal of Clinical Practice, vol.35, issue.Suppl. 3, pp.61-2030, 2007.
DOI : 10.1176/jnp.9.3.315

H. Manji, J. Quiroz, J. Sporn, J. Payne, K. Denicoff et al., Enhancing neuronal plasticity and cellular resilience to develop novel, improved therapeutics for Difficult-to-Treat depression, Biological Psychiatry, vol.53, issue.8, pp.707-742, 2003.
DOI : 10.1016/S0006-3223(03)00117-3

P. Masand, Tolerability and adherence issues in antidepressant therapy, Clinical Therapeutics, vol.25, issue.8, pp.2289-2304, 2003.
DOI : 10.1016/S0149-2918(03)80220-5

V. Micale, A. Arezzi, L. Rampello, and F. Drago, Melatonin affects the immobility time of rats in the forced swim test: The role of serotonin neurotransmission, European Neuropsychopharmacology, vol.16, issue.7, pp.538-545, 2006.
DOI : 10.1016/j.euroneuro.2006.01.005

M. Millan, The role of monoamines in the actions of established and ???novel??? antidepressant agents: a critical review, European Journal of Pharmacology, vol.500, issue.1-3, pp.371-384, 2004.
DOI : 10.1016/j.ejphar.2004.07.038

M. Millan, Multi-target strategies for the improved treatment of depressive states: Conceptual foundations and neuronal substrates, drug discovery and therapeutic application, Pharmacology & Therapeutics, vol.110, issue.2, pp.135-370, 2006.
DOI : 10.1016/j.pharmthera.2005.11.006

M. Millan, F. Lejeune, and A. Gobert, Reciprocal autoreceptor and heteroreceptor control of serotonergic, dopaminergic and noradrenergic transmission in the frontal cortex: relevance to the actions of antidepressant agents, Journal of Psychopharmacology, vol.24, issue.2, pp.114-138, 2000.
DOI : 10.1016/0169-328X(91)90064-5

M. Millan, M. Brocco, A. Gobert, and A. Dekeyne, Anxiolytic properties of agomelatine, an antidepressant with melatoninergic and serotonergic properties: role of 5-HT2C receptor blockade, Psychopharmacology, vol.35, issue.4, pp.448-458, 2005.
DOI : 10.1007/s00213-004-1962-z

M. Millan, A. Gobert, F. Lejeune, A. Dekeyne, A. Newman-tancredi et al., The Novel Melatonin Agonist Agomelatine (S20098) Is an Antagonist at 5-Hydroxytryptamine2C Receptors, Blockade of Which Enhances the Activity of Frontocortical Dopaminergic and Adrenergic Pathways, Journal of Pharmacology and Experimental Therapeutics, vol.306, issue.3, pp.954-964, 2003.
DOI : 10.1124/jpet.103.051797

S. Mir and D. Taylor, The adverse effects of antidepressants, Current Opinion in Psychiatry, vol.10, issue.2, pp.88-94, 1997.
DOI : 10.1097/00001504-199703000-00006

M. Moller and F. Baeres, The anatomy and innervation of the mammalian pineal gland, Cell and Tissue Research, vol.309, issue.1, pp.139-50, 2002.
DOI : 10.1007/s00441-002-0580-5

A. Montejo, G. Llorca, J. Izquierdo, and F. Rico-villademoros, Incidence of sexual dysfunction associated with antidepressant agents: a prospective multicenter study of 1022 outpatients, J Clin Psychiatry, vol.62, issue.3, pp.10-21, 2001.

P. Monteleone and M. Maj, The circadian basis of mood disorders: Recent developments and treatment implications, European Neuropsychopharmacology, vol.18, issue.10, pp.701-711, 2008.
DOI : 10.1016/j.euroneuro.2008.06.007

S. Montgomery, Major depressive disorders: clinical efficacy and tolerability of agomelatine, a new melatonergic agonist, European Neuropsychopharmacology, vol.16, pp.633-638, 2006.
DOI : 10.1016/S0924-977X(06)70009-8

S. Montgomery and Y. Lecrubier, Is severe depression a separate indication?1Chair: SA Montgomery, Y. Lecrubier.Participants: E. Abadie, M. Ackenheil, J. Angst, P. Bech, P. Bouka, M. Briley, S. Eisen, J.-D. Guelfi, S. Kasper, J. Keogeorgos, B. Picon, R.M. Pinder, A. Puech, A. Sitzen, C.R. Soldatos, J.M. Van Ree, B.J. Van Zwieten-Boot.Rapporteur: D.B. Montgomery.1, European Neuropsychopharmacology, vol.9, issue.3, pp.259-264, 1999.
DOI : 10.1016/S0924-977X(98)00048-0

S. Montgomery, D. Baldwin, and A. Riley, Antidepressant medications: a review of the evidence for drug-induced sexual dysfunction, Journal of Affective Disorders, vol.69, issue.1-3, pp.119-159, 2002.
DOI : 10.1016/S0165-0327(01)00313-5

S. Montgomery, S. Kennedy, G. Burrows, M. Lejoyeux, and I. Hindmarch, Absence of discontinuation symptoms with agomelatine and occurrence of discontinuation symptoms with paroxetine: a randomized, double-blind, placebo-controlled discontinuation study, International Clinical Psychopharmacology, vol.19, issue.5, pp.271-280, 2004.
DOI : 10.1097/01.yic.0000137184.64610.c8

P. Morgan, P. Barrett, H. Howell, and R. Helliwell, Melatonin receptors: Localization, molecular pharmacology and physiological significance, Neurochemistry International, vol.24, issue.2, pp.101-146, 1994.
DOI : 10.1016/0197-0186(94)90100-7

D. Morilak and A. Frazer, Antidepressants and brain monoaminergic systems: a dimensional approach to understanding their behavioural effects in depression and anxiety disorders, The International Journal of Neuropsychopharmacology, vol.7, issue.2
DOI : 10.1017/S1461145704004080

O. Nosjean, M. Ferro, and F. Coge, as the Quinone Reductase 2, Journal of Biological Chemistry, vol.261, issue.40, pp.31311-31317, 2000.
DOI : 10.1074/jbc.275.12.8794

M. Olfson, S. Marcus, M. Tedeschi, and G. Wan, Continuity of Antidepressant Treatment for Adults With Depression in the United States, American Journal of Psychiatry, vol.163, issue.1, pp.101-108, 2006.
DOI : 10.1176/appi.ajp.163.1.101

J. Olié and S. Kasper, Efficacy of agomelatine, a MT1/MT2 receptor agonist with 5-HT2C antagonistic properties, in major depressive disorder, Int J Neuropsychopharmacol, vol.10, issue.5, pp.661-673, 2007.

C. Pacchierotti, S. Iapichino, and L. Bossini, Melatonin in Psychiatric Disorders: A Review on the Melatonin Involvement in Psychiatry, Frontiers in Neuroendocrinology, vol.22, issue.1, pp.18-32, 2001.
DOI : 10.1006/frne.2000.0202

S. Pandi-perumal, N. Zisapel, V. Srinivasan, and D. Cardinali, Melatonin and sleep in aging population, Experimental Gerontology, vol.40, issue.12, pp.911-925, 2005.
DOI : 10.1016/j.exger.2005.08.009

G. Papakostas, R. Perlis, M. Scalia, T. Petersen, and M. Fava, A Meta-Analysis of Early Sustained Response Rates Between Antidepressants and Placebo for the Treatment of Major Depressive Disorder, Journal of Clinical Psychopharmacology, vol.26, issue.1, pp.56-60, 2006.
DOI : 10.1097/01.jcp.0000195042.62724.76

M. Papp, P. Gruca, P. Boyer, and E. Mocaer, Effect of Agomelatine in the Chronic Mild Stress Model of Depression in the Rat, Neuropsychopharmacology, vol.17, issue.Suppl, pp.694-703, 2003.
DOI : 10.3928/0048-5713-19871001-11

D. Perahia, D. Kajdasz, D. Desaiah, and P. Haddad, Symptoms following abrupt discontinuation of duloxetine treatment in patients with major depressive disorder, Journal of Affective Disorders, vol.89, issue.1-3, pp.207-212, 2005.
DOI : 10.1016/j.jad.2005.09.003

P. Pévet, Melatonin: From Seasonal to Circadian Signal, Journal of Neuroendocrinology, vol.876, issue.4, pp.422-426, 2003.
DOI : 10.1016/S0006-8993(00)02590-7

R. Pinder, Designing a new generation of antidepressant drugs, Acta Psychiatrica Scandinavica, vol.277, issue.s391, pp.7-13, 1997.
DOI : 10.1097/00004850-199512004-00006

M. Quera-salva, B. Vanier, and F. Chapotot, Effect of agomelatine on the sleep EEG in patients with major depressive disorders, Eur Neuropsychopharmacol, vol.15, issue.3, pp.435-442, 2005.

J. Redman and A. Francis, Entrainment of Rat Circadian Rhythms by the Melatonin Agonist S-20098 Requires Intact Suprachiasmatic Nuclei But Not the Pineal, Journal of Biological Rhythms, vol.9, issue.1, pp.39-51, 1998.
DOI : 10.1016/0006-8993(93)90682-D

R. Reiter and . Pineal-melatonin, Pineal Melatonin: Cell Biology of Its Synthesis and of Its Physiological Interactions*, Endocrine Reviews, vol.12, issue.2, pp.151-180, 1991.
DOI : 10.1210/edrv-12-2-151

R. Reiter, The pineal gland and melatonin in relation to aging: A summary of the theories and of the data, Experimental Gerontology, vol.30, issue.3-4, pp.199-212, 1995.
DOI : 10.1016/0531-5565(94)00045-5

R. Reiter, Oxidative damage in the central nervous system: protection by melatonin, Progress in Neurobiology, vol.56, issue.3, pp.359-384, 1998.
DOI : 10.1016/S0301-0082(98)00052-5

M. Reppert, D. Weaver, and C. Godson, Melatonin receptors step into the light: cloning and classification of subtypes, Trends in Pharmacological Sciences, vol.17, issue.3, pp.100-102, 1996.
DOI : 10.1016/0165-6147(96)10005-5

P. Riederer, L. Lachenmayer, and G. Laux, Clinical Applications of MAO-Inhibitors, Current Medicinal Chemistry, vol.11, issue.15, pp.2033-2043, 2004.
DOI : 10.2174/0929867043364775

N. Rosenthal, D. Sack, J. Gillin, A. Lewy, F. Goodwin et al., Seasonal Affective Disorder, Archives of General Psychiatry, vol.41, issue.1, pp.72-80, 1984.
DOI : 10.1001/archpsyc.1984.01790120076010

F. Rouillon, Efficacy and tolerance profile of agomelatine and practical use in depressed patients, International Clinical Psychopharmacology, vol.21, issue.Supplement 1, pp.31-35, 2006.
DOI : 10.1097/01.yic.0000195659.99148.09

P. Sagaspe, M. Sanchez-ortuno, A. Charles, J. Taillard, C. Valtat et al., Effects of sleep deprivation on Color-Word, Emotional, and Specific Stroop interference and on self-reported anxiety, Brain and Cognition, vol.60, issue.1, pp.76-87, 2006.
DOI : 10.1016/j.bandc.2005.10.001

L. San and B. Arranz, Agomelatine: A novel mechanism of antidepressant action involving the melatonergic and the serotonergic system, European Psychiatry, vol.23, issue.6, pp.396-402, 2008.
DOI : 10.1016/j.eurpsy.2008.04.002

L. Santarelli, S. M. Gross, C. Surget, A. Battaglia, F. Dulawa et al., Requirement of Hippocampal Neurogenesis for the Behavioral Effects of Antidepressants, Science, vol.301, issue.5634, pp.805-809, 2003.
DOI : 10.1126/science.1083328

A. Schatzberg, Pharmacological principles of antidepressant efficacy, Human Psychopharmacology: Clinical and Experimental, vol.59, issue.S1, pp.17-22, 2002.
DOI : 10.4088/JCP.v59n0606

U. Schibler and F. Naef, Cellular oscillators: rhythmic gene expression and metabolism, Current Opinion in Cell Biology, vol.17, issue.2, pp.223-229, 2005.
DOI : 10.1016/j.ceb.2005.01.007

V. Simonneaux, V. Poirel, M. Garidou, D. Nguyen, E. Diaz-rodriguez et al., Daily rhythm and regulation of clock gene expression in the rat pineal gland, Molecular Brain Research, vol.120, issue.2, pp.164-172, 2004.
DOI : 10.1016/j.molbrainres.2003.10.019

S. Sonawalla and M. Fava, Severe Depression, CNS Drugs, vol.79, issue.3, pp.765-776, 2001.
DOI : 10.2165/00023210-200115100-00003

V. Srinivasan, S. Pandi-perumal, I. Trakht, D. Spence, R. Hardeland et al., Pathophysiology of depression: Role of sleep and the melatonergic system, Psychiatry Research, vol.165, issue.3, pp.201-214, 2009.
DOI : 10.1016/j.psychres.2007.11.020

A. Szegedi, M. Muller, I. Anghelescu, C. Klawe, R. Kohnen et al., Early Improvement Under Mirtazapine and Paroxetine Predicts Later Stable Response and Remission With High Sensitivity in Patients With Major Depression, The Journal of Clinical Psychiatry, vol.64, issue.4, pp.413-420, 2003.
DOI : 10.4088/JCP.v64n0410

M. Taylor, L. Rudkin, and K. Hawton, Strategies for managing antidepressant-induced sexual dysfunction: Systematic review of randomised controlled trials, Journal of Affective Disorders, vol.88, issue.3, pp.241-254, 2005.
DOI : 10.1016/j.jad.2005.07.006

Y. Touitou, Dysfonctionnements de l???horloge biologique et leurs traitements, Annales Pharmaceutiques Fran??aises, vol.66, issue.3, pp.146-157, 2008.
DOI : 10.1016/j.pharma.2008.05.001

M. Trivedi, A. Rush, B. Gaynes, J. Stewart, S. Wisniewski et al., Maximizing the Adequacy of Medication Treatment in Controlled Trials and Clinical Practice: STAR*D Measurement-Based Care, Neuropsychopharmacology, vol.58, issue.12, pp.2479-2489, 2007.
DOI : 10.1136/jamia.1995.96073834

M. Trivedi, A. Rush, S. Wisniewski, A. Nierenberg, D. Warden et al., Evaluation of Outcomes With Citalopram for Depression Using Measurement-Based Care in STAR*D: Implications for Clinical Practice, American Journal of Psychiatry, vol.163, issue.1, pp.28-40, 2006.
DOI : 10.1176/appi.ajp.163.1.28

F. Turek and M. Gillette, Melatonin, sleep, and circadian rhythms: rationale for development of specific melatonin agonists, Sleep Medicine, vol.5, issue.6, pp.523-532, 2004.
DOI : 10.1016/j.sleep.2004.07.009

V. Valentini, R. Frau, D. Chiara, and G. , Noradrenaline transporter blockers raise extracellular dopamine in medial prefrontal but not parietal and occipital cortex: differences with mianserin and clozapine, Journal of Neurochemistry, vol.412, issue.4, pp.917-927, 2004.
DOI : 10.1007/s00213-002-1381-y

O. Van-reeth, L. Weibel, E. Olivares, S. Maccari, E. Mocaer et al., Melatonin or a melatonin agonist corrects age-related changes in circadian response to environmental stimulus, American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, vol.263, issue.5, pp.1582-1591, 2001.
DOI : 10.1016/0306-4522(95)00408-4

A. Wade and A. Friis, The onset of effect for escitalopram and its relevance for the clinical management of depression, Current Medical Research and Opinion, vol.22, issue.11, pp.2101-2110, 2006.
DOI : 10.1185/030079906X148319

F. Waldhauser, B. Ehrhart, and E. Forster, Clinical aspects of the melatonin action: impact of development, aging, and puberty, involvement of melatonin in psychiatric disease and importance of neuroimmunoendocrine interactions, Experientia, vol.123, issue.2, pp.671-81, 1993.
DOI : 10.1001/archpsyc.1986.01800090060008

T. Wehr, Photoperiodism in Humans and Other Primates: Evidence and Implications, Journal of Biological Rhythms, vol.85, issue.1, pp.348-64, 2001.
DOI : 10.1111/j.1469-7793.2000.00695.x

M. Weissman, R. Bland, G. Canino, C. Faravelli, S. Greenwald et al., Cross-National Epidemiology of Major Depression and Bipolar Disorder, JAMA: The Journal of the American Medical Association, vol.276, issue.4, pp.293-299, 1996.
DOI : 10.1001/jama.1996.03540040037030

J. Wiley, M. Dance, and R. Balster, Preclinical evaluation of the reinforcing and discriminative stimulus effects of agomelatine (S-20098), a melatonin agonist, Psychopharmacology, vol.140, issue.4, pp.503-509, 1998.
DOI : 10.1007/s002130050795

P. Willner, A. Hale, and S. Argyropoulos, Dopaminergic mechanism of antidepressant action in depressed patients, Journal of Affective Disorders, vol.86, issue.1, pp.37-45, 2005.
DOI : 10.1016/j.jad.2004.12.010

A. Wirz-justice, Chronobiology and mood disorders, Dialogues in Clin Neurosci, vol.5, pp.315-325, 2003.

H. Wittchen and F. Jacobi, Size and burden of mental disorders in Europe???a critical review and appraisal of 27 studies, European Neuropsychopharmacology, vol.15, issue.4, pp.357-376, 2005.
DOI : 10.1016/j.euroneuro.2005.04.012

M. Wood, C. Reavill, B. Trail, A. Wilson, T. Stean et al., SB-243213; a selective 5-HT2C receptor inverse agonist with improved anxiolytic profile: lack of tolerance and withdrawal anxiety, Neuropharmacology, vol.41, issue.2, pp.186-199, 2001.
DOI : 10.1016/S0028-3908(01)00054-5

B. Zawilska, M. Berezinska, J. Rosiak, B. Vivien-roels, D. Skene et al., Daily variation in the concentration of melatonin and 5-methoxytryptophol in the goose pineal gland, retina, and plasma, General and Comparative Endocrinology, vol.134, issue.3, pp.296-302, 2003.
DOI : 10.1016/S0016-6480(03)00269-7

A. Annexe, Critères de l'épisode dépressif majeur selon le DSM-IV A Au moins 5 des symptômes suivants doivent avoir été présents pendant une même période d'une durée de 2 semaines et avoir représenté un changement par rapport au fonctionnement antérieur ; au moins 1 des symptômes est soit

B. Présence-d, au moins 2 des 3 symptômes suivants : (1) Humeur dépressive à un degré nettement anormal pour le sujet, présente pratiquement toute la journée et presque tous les jours, dans une large mesure non influencée par les circonstances