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Agomelatina: un fármaco nuevo con acción antidepresiva que afecta a los sistemas melatonérgico y serotonérgico

Published online by Cambridge University Press:  12 May 2020

Luis San  and
Belen Arranz
Luis San
Affiliation:
Departamento de Psiquiatría, Hospital San Rafael, Barcelona, España.
Belen Arranz
Affiliation:
Servicios de Salud Mental, San Juan de Dios, Antoni Pujades, 42, 08830, Sant Boi de Llobregat, Barcelona, España.
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Resumen

La observavión clínica de que los trastornos depresivos a menudo se asocian con desincronización de los ritmos internos ha reforzado la idea de que recuperar los ritmos circadianos normales puede tener algún potencial antidepresivo. Agomelatina, un naftaleno análogo de melatonina, es a la vez agonista de los receptores humanos melatonérgicos MT1 y MT2 y antagonista de los receptores de serotonina 5-HT2C. Agomelatina combina la actividad sincronizadora (zeitgeber en alemán, sincronizador del sistema circadiano) con su capacidad de aumentar la neurotransmisión (aumenta las concentraciones de dopamina y noradrenalina en la corteza frontal). Se ha demostrado la eficacia de agomelatina en el tratamiento de la depresión en tres estudios a corto plazo, aleatorios y controlados por placebo. Estos estudios demostraron que agomelatina es eficaz en el trastorno depresivo mayor en una dosis estándar de 25 mg/día, con la posibilidad de aumentar la dosis a 50 mg/día en pacientes con mejoría insuficiente. El número de efectos adversos durante el período de tratamiento fue similar al del placebo. Cuatro estudios han demostrado el efecto positivo de agomelatina sobre la continuidad y la calidad del sueño y el acortamiento de la latencia del sueño. A pesar de que estos datos son prometedores, son necesarios otros estudios para examinar la eficacia de agomelatina durante un período de tratamiento más largo.

Keywords

Ritmos circadianosDepresiónTrastornos del sueñoMelatoninaAgomelatina
Type
Revisión
Information
European Psychiatry (Ed. Española) , Volume 15 , Issue 8 , November 2008 , pp. 375 - 381
Copyright
Copyright © European Psychiatric Association 2008

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References

Bibliografía

Alonso, JAngermeyer, MCLepine, JP. The European study of the Epidemiology of mental disorders (ESEMeD) project. Acta Psychiatr Scand 2004; 420: 5–7.CrossRefGoogle Scholar
Agid, YBuzsaki, GDiamond, DMFrackowiak, RGiedd, JGirault, JA et al. How can drug discovery for psychiatric disorders be improved? Nat Rev Drug Discov 2007;6:189–201.CrossRefGoogle ScholarPubMed
Boivin, DB. Inñuence of sleep-wake and circadian rhythm disturbarnos in psychiatric disorders. J Psychiatry Neurosci 2000;35:446-58.Google Scholar
Brainard, GCHanifin, JPGreeson, JMByrne, BGlickman, GGerner, E et al. Action spectrum for melatonin regulation in humans: evidence for a novel circadian photoreceptor. J Neurosci 2002;21: 6405–12.CrossRefGoogle Scholar
Barden, NShink, ELabbé, MVacher, RRochford, JMocaer, E.Antidepressant action of agomelatine (S 20098) in a transgenic mouse model. Prog Neuropsychopharmacol Biol Psychiatry 2005; 29:908-16.CrossRefGoogle Scholar
Benca, RMObermeyer, WHThisted, RAGillin, JC.Sleep and psychiatric disorders. A meta-analysis. Arch Gen Psychiatry 1992;49: 651–68.CrossRefGoogle ScholarPubMed
Claustral, BChazot, GBrun, JJordán, DSassolas, G. A chronobiological study of melatonin and cortisol secretion in depressed subjects: plasma melatonin, a biochemical marker in major depression. Biol Psychiatry 1984; 19: 1215–28.Google Scholar
Crasson, MKjiri, SColin, AKriri, KL'Hermite-Baleriaux, MAnsseau, M et al. Serum melatonin and urinary 6-sulphatoxymelatonin in major depression. Psychoneuroendocrinology 2004;29:1–12.CrossRefGoogle ScholarPubMed
Carvalho, LAGorenstein, CMoreno, RAMarkus, RP. Melatonin levels in drug-free patients with major depression from the Southern hemisphere. Psychoneuroendocrinology 2006; 31: 761–8.CrossRefGoogle ScholarPubMed
Calabrese, JRGuelfi, JDPerdrizet-Chevallier, C. Agomelatine bipolar study group. Agomelatine adjunctive therapy for acute bipolar depression: preliminary open data. Bipolar Disord 2007;9:628–35.CrossRefGoogle Scholar
Colé, MGDendukuri, N.Risk factors for depression among elderly community subjects: a systematic review and meta-analysis. Am J Psychiatry 2003;160:1147–56.CrossRefGoogle ScholarPubMed
Cajochen, CKrauchi, KMori, DGraw, PWirz-Justice, A. Melatonin and S-20098 increase REM sleep and wake-up propensity without modifying NREM sleep homeostasis. Am J Physiol 1997;272(4 Pt. 2):R1189-96.Google ScholarPubMed
Dalton, EJRotondi, DLevitan, RDKennedy, SHBrown, GM. Use of slow-release melatonin in treatment-resistant depression. J Psychiatry Neurosci 2000;25:48–52.Google ScholarPubMed
Delagrange, PBoutin, JA. Therapeutic potential of melatonin ligands. Chronobiol Int 2006;23:413–8.CrossRefGoogle ScholarPubMed
Dubocovich, ML. Drug evaluation: agomelatine targets a range of major depressive disorder symptoms. Curr Opin Investig Drugs 2006;7:670–80.Google ScholarPubMed
Gruta, PPrzegalinski, EMrowiec, SLason, MPapp, M. Evidence for antidepressant and anxiolytic-like activities of melatonin and agomelatine in animal models. Eur Neuropsychopharmacol 2004; 14: S230.Google Scholar
Gurevich, ITamir, HArango, VDwork, AJMann, JJSchmauss, C.Altered editing of serotonin 2C receptor pre-mRNA in the prefrontal cortex of depressed suicide victims. Neuron 2002;34:349–56.CrossRefGoogle ScholarPubMed
Hattar, SLucas, RJMrosovsky, NThompson, SDouglas, RHHankins, MW et al. Melanopsin and rod-cone photoreceptive systems account for all major accessory visual functions in mice. Nature 2003;424:76–81.CrossRefGoogle ScholarPubMed
Holmes, MCFrench, KLSeckl, JR. Dysregulation of diurnal rhythms of serotonin 5-HT2C and cortícosteroid receptor gene expression in the hippocampus with food restriction and glucocorticoids. J Neurosci 1997;17:4056–65.CrossRefGoogle ScholarPubMed
Hanoun, NMocaer, EBoyer, PAHamon, MLanfumey, L. Differential effects of the novel antidepressant agomelatine (S 20098) versus fluoxetine on 5-HT1A receptors in the rat brain. Neuropharmacology 2004;47:515–26.CrossRefGoogle ScholarPubMed
Kessler, RCChin, WTDemler, OWalters, EE. Prevalence, severity and comorbidity of twelve month DSM IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005;62: 617–27.CrossRefGoogle ScholarPubMed
Kennaway, DJMoyer, RWVoultsios, AVarcoe, TJ. Serotonin, excitatory amino acids and the photic control of melatonin rhythms and SCN c-FOS in the rat. Brain Res 2001;897:36–43.CrossRefGoogle ScholarPubMed
Kenuaway, DJMoyer, RW. Serotonin 5-HT2c agonists mimic the effect of light pulses on circadian rhythms. Brain Res 1998;806: 257–70.CrossRefGoogle Scholar
Kennedy, SEmsley, RA. Placebo—controlled trial of agomelatine in the treatment of major depressive disorder. Eur Neuropsychopharmacol 2006;16(2):93–100.CrossRefGoogle ScholarPubMed
Leproult, RVan Onderbergen, AL'Hermite-Baleriaux, MVan Cauter, ECopinschi, G.Phase-shifts of 24-h rhythms of hormonal rele ase and body temperatura following early evening administration of the melatonin agonist agomelatine in healthy older men. Clin Endocrinol 2005;63:298–304.CrossRefGoogle Scholar
Loo, HHale, AD'Haenen, H. 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 2002;17:239–47.Google Scholar
Lopes, MCQuera-Salva, MAGuilleminault, C. Cyclic alternating pattern in the nREM sleep of patients with major depressive disorder: baseline results and change overtime with a new antidepressant: agomelatine. Sleep Med 2005;6(Suppl. 2):87–8.Google Scholar
Moore, RY. Circadian rhythms: basic neurobiology and clinical applications. Annu Rev Med 1997;48:253–66.CrossRefGoogle ScholarPubMed
Macchi, MMBruce, JN. Human pineal physiology and functional significance of melatonin. Front Neuroendocrinol 2004;25:177–95.CrossRefGoogle ScholarPubMed
Millan, MJGobert, ALejeune, FDekeyne, ANewman-Tancredi, APasteau, V et al. The novel melatonin agonist agomelatine (S20098) is an antagonist at 5-hydroxytryptamine 2C receptors, blockade of which enhances the activity of frontocortical dopaminergic and adrenergic pathways. J Pharmacol Exp Ther 2003;306:954–64.CrossRefGoogle ScholarPubMed
Masana, MIBenloucif, SDubocovich, ML. Circadian rhythm of MT1 melatonin receptor expression in the suprachiasmatic nucleus of the C3H/HeN mouse. J Pineal Res 2000;28:185–92.CrossRefGoogle ScholarPubMed
Martinet, LGuardiola-Lemaitre, BMocaer, E. Entrainment of circadian rhythms by S-20098, a melatonin agonist, is dose and plasma concentration dependent. Pharmacol Biochem Behav 1996;54:713-8.CrossRefGoogle ScholarPubMed
Millan, MJBroceo, MGobert, ADekeyne, A. Anxiolytic properties of agomelatine, an antidepressant with melatoninergic and serotonergic properties: role of 5-HT2C receptor blockade. Psychopharmacology (Berl) 2005;177:448–58.CrossRefGoogle ScholarPubMed
Montgomery, SAKasper, S. Severe depression and antidepressants: focus on a pooled analysis of placebo—controlled studies on agomelatine. Int Clin Psychopharmacol 2007;22:283–91.CrossRefGoogle ScholarPubMed
Montgomery, SAKennedy, SHBurrows, GDLejoyeux, MHindmarch, I. 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.CrossRefGoogle ScholarPubMed
Olié, JPKasper, S.Efficacy of agomelatine, a MT1/MT2 receptor agonist with 5-HT2C antagonistic properties, in major depressive disorder. Int J Neuropsychopharmacol 2007;10(5):661–73.Google ScholarPubMed
Pandi-Perumal, SRSrinivasan, VMaestroni, GJMCardinal, DPPoeggeler, BHardeland, R.Melatonin: nature's most versatile biological signal? FEBS J 2006;273:2813–38.CrossRefGoogle ScholarPubMed
Pandi-Perumal, SRSrinivasan, VSpence, DWCardinali, DP.Role of melatonin system in the control of sleep. CNS Drugs 2007;21(12): 995–1018.CrossRefGoogle Scholar
Paccierotti, CIapichino, SBossini, LPieraccini, FCastrogiovanni, P. Melatonin in psychiatric disorders: a review on the melatonin involvement in psychiatry. Front Neuroendocrinol 2001;22:18–32.CrossRefGoogle Scholar
Palazidou, EPapadopoulos, ARatcliff, HDawling, SCheckley, SA. Noradrenaline uptake inhibition increases melatonin secretion, a measure of noradrenergic neurotransmission, in depressed patients. Psychol Med 1992;22:309–15.CrossRefGoogle ScholarPubMed
Papp, MGruta, PBoyer, PAMocaer, E. Effect of agomelatine in the chronic mild stress model of depression in the rat. Neuropsychopharmacology 2003;28:694–703.CrossRefGoogle ScholarPubMed
Pitrosky, BKirsch, RMalan, AMocaer, EPevert, POrganisation of rat circadian rhythms during daily infusión of melatonin or S20098, a melatonin agonist. Am J Physiol 1999;277:812–28.Google ScholarPubMed
Papp, MLitwa, EGruta, PMocaer, E. Anxiolytic-like activity of agomelatine and melatonin in three animal models of anxiety. Behav Pharmacol 2006;17:9–18.Google ScholarPubMed
Quera-Salva, MAVanier, BLaredo, JHartley, SChapopot, FMoulin, C et al. Major depressive disorder, sleep EEG and agomelatine: an open-label study. Int J Neuropsychopharmacol 2007; 10(5):691–6.Google ScholarPubMed
Riedel, WJKlaassen, TGriez, EHonig, AMenheere, PPCAVan Praag, HM.Dissociable hormonal, cognitive and mood responses to neuroendocrine challenge: evidence for receptor-specific serotonergic dysregulation in depressed mood. Neuropsychopharmacology 2002;26:358–67.CrossRefGoogle ScholarPubMed
Redman, JRGuardiola-Lemaitre, BBrown, MDelagrange, PArmstrong, SM. Dose dependent effects of S-20098, a melatonin agonist, on direction of re-entrainment of rat circadian activity rhythms. Psychopharmacology (Berl) 1995;118:385–90.CrossRefGoogle ScholarPubMed
Riemann, DBerger, MVodelholzer, U. Sleep and depression; results from psychobiological studies: an overview. Biol Psychol 2001;57: 67–103.CrossRefGoogle ScholarPubMed
Schildkraut, JJ. The catecholamine hypothosis of affective disorders: a review of supporting evidence. Am J Psychiatry 1965;122:509–22.CrossRefGoogle Scholar
Turek, FW. From circadian rhythms to clock genes in depression. Int Clin Psychopharmacol 2007;22(Suppl. 2):Sl–8.CrossRefGoogle ScholarPubMed
Tsujimoto, TYamada, NShimoda, KKanada, KTakahashi, S. Circadian rhythms in depression. Part II: circadian rhythms in inpatients with various mental disorders. J Affect Disord 1990; 18:199–210.CrossRefGoogle ScholarPubMed
Van Cauter, ELeproult, RKupfer, DJ.Effects of gender and age on the levéis and circadian rhythmicity of plasma cortisol. J Clin Endocrino) Metab 1996;81:2468–73.Google Scholar
Van Reeth, OWeibel, LOlivares, EMaccari, SMocaer, ETurek, FW.Melatonin or a melatonin agonist corrects age-related changes in circadian response to environmental stimulus. Am J Physiol Regul Integr Comp Physiol 2001;280:1582–91.CrossRefGoogle ScholarPubMed
Varcoe, TJKennaway, DJVoultsios, A. Activation of 5-HT2C receptors acutely induces per gene expression in the rat suprachiasmatic nucleus at night. Brain Res Mol Brain Res 2003;119:192–200.CrossRefGoogle ScholarPubMed
Wells, KBStewart, AHays, RDBurnam, MARogers, WDaniels, M et al. The functioning and well-being of depressed patients: results from the medical outcomes study. JAMA 1989;262:914–9.CrossRefGoogle ScholarPubMed
Wehr, TAWirz-Justice, A. Circadian rhythm mechanisms in affective illness and in antidepressant drug action. Pharmacopsychiatria 1982;15:31–9.CrossRefGoogle ScholarPubMed
Wirz-Justice, A.Biological rhythm disturbances in mood disorders. Int Clin Psychopharmacol 2006;21:11–5.CrossRefGoogle ScholarPubMed
Yamada, JSugimoto, Y. Effects of 5-HT2 receptor antagonists on the antiimmobility effects of imipramine in the forced swimming test with mice. Eur J Pharmacol 2001;427:221–5.CrossRefGoogle Scholar
Zupancic, MGuilleminault, C. Agomelatine: a preliminary review of a new antidepressant. CNS Drugs 2006;20(12):981–92.CrossRefGoogle ScholarPubMed