Agomelatine in pharmacological and neurological assessments – safety and clinical use Review article
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Published:
Jun 30, 2021
Keywords:
depression, antidepressants, agomelatine, safety of therapy
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Abstract
Depression is a wide-spread and in many cases lifelong condition that has a dramatic impact on patients, their families, and the healthcare system. Even though the pathophysiology of depression is not fully explored, it is increasingly considered that monoamine deficiencies may not be the only pathogenetic pathway. Agomelatine, as an agonist of the melatonergic MT1 and MT2 receptors, and as a 5-HT2C receptor antagonist, is an antidepressant with a unique mechanism of action. In large placebo-controlled trials, depression symptoms significantly improved with agomelatine as compared to placebo, thus agomelatine appears to be as effective in treating major depressive disorder as other antidepressants. Concerns have been raised about the drug's potential to cause liver damage since it was introduced in 2009. Therefore, a comprehensive assessment of the potential risk of liver injury from agomelatine by reviewing data from newly published clinical trials is needed.
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References
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2. Millan MJ, Gobert A, Lejeune F et al. The novel melatonin agonist agomelatine (S20098) is an antagonist at 5-hydroxy – suggestion that chronic sleep disruption and chronic tryptamine 2C receptors, blockade of which enhances the insomnia can lead to depression; the demonstration activity of frontocortical dopaminergic and adrenergic pathways. J Pharmacol Exp Ther. 2003; 306(3): 954-64.
3. Millan MJ, Marin P, Kamal M et al. The melatonergic agonist and clinically active antidepressant, agomelatine, is a neutral antagonist at 5-HT(2C) receptors. Int J Neuropsychopharmacol. 2011; 14(6): 768-83.
4. Zupancic M, Guilleminault C. Agomelatine: a preliminary review of a new antidepressant. CNS Drugs. 2006; 20(12): 981-92.
5. Tchekalarova J, Stoynova T, Ilieva K et al. Agomelatine treatment corrects symptoms of depression and anxiety by restoring the disrupted melatonin circadian rhythms of rats exposed to chronic constant light. Pharmacol Biochem Behav. 2018; 171: 1-9.
6. Thomas J, Khanam R, Vohora D. Augmentation of antidepressant effects of venlafaxine by agomelatine in mice are independent of kynurenine pathway. Neurochem Int. 2016; 99: 103-9.
7. Soumier A, Banasr 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.
8. Yucel A, Yucel N, Ozkanlar S et al. Effect of agomelatine on adult hippocampus apoptosis and neurogenesis using the stress model of rats. Acta Histochem. 2016; 118: 299-304.
9. Pandi-Perumal SR, Srinivasan V, Cardinali DP et al. Could agomelatine be the ideal antidepressant? Expert Rev Neurother. 2006; 6(11): 1595-608.
10. Agomelatine. Summary of product characteristics. 2013.
11. Kennedy SH, Avedisova A, Giménez-Montesinos N et al; Agomelatine Study Group. A placebo-controlled study of three agomelatine dose regimens (10 mg, 25 mg, 25–50 mg) in patients with major depressive disorder. Eur Neuropsychopharmacol. 2014; 24: 553-63.
12. Taylor D, Sparshatt A, Varma S et al. Antidepressant efficacy of agomelatine: meta-analysis of published and unpublished studies. BMJ. 2014; 348: g1888.
13. Pae CU, Wang SM, Han C et al. Vortioxetine: a meta-analysis of 12 short-term, randomized, placebo-controlled clinical trials for the treatment of major depressive disorder. J Psychiatry Neurosci. 2015; 40: 174-86.
14. Vinckier F, Gourion D, Mouchabac S. Anhedonia predicts poor psychosocial functioning: results from a large cohort of patients treated for major depressive disorder by general practitioners. Eur Psychiatry. 2017; 44: 1-8.
15. Fornaro M, McCarthy MJ, De Berardis D et al. Adjunctive agomelatine therapy in the treatment of acute bipolar II depression: a preliminary open label study. Neuropsychiatr Dis Treat. 2013; 9: 243-51.
16. Calandre EP, Slim M, Garcia-Leiva JM et al. Agomelatine for the treatment of patients with fibromyalgia and depressive symptomatology: an uncontrolled, 12-week, pilot study. Pharmacopsychiatry. 2014; 47: 67-72.
17. Corruble E, de Bodinat C, Belaïdi C et al.; Agomelatine study group. Efficacy of agomelatine and escitalopram on depression, subjective sleep and emotional experiences in patients with major depressive disorder: a 24-wk randomized, controlled, double- blind trial. Int J Neuropsychopharmacol. 2013; 16: 2219-34.
18. Montgomery SA, Nielsen RZ, Poulsen LH et al. A randomised, double-blind study in adults with major depressive disorder with an inadequate response to a single course of selective serotonin reuptake inhibitor or serotonin–noradrenaline reuptake inhibitor treatment switched to vortioxetine or agomelatine. Hum Psychopharmacol. 2014; 29: 470-82.
19. Kennedy SH, Avedisova A, Belaïdi C et al. Sustained efficacy of agomelatine 10 mg, 25 mg, and 25–50 mg on depressive symptoms and functional outcomes in patients with major depressive disorder. A placebo-controlled study over 6 months. Eur Neuropsychopharmacol. 2016; 26: 378-89.
20. Shu L, Sulaiman AH, Huang YS et al. Comparable efficacy and safety of 8 weeks treatment with agomelatine 25–50 mg or fluoxetine 20–40 mg in Asian out-patients with major depressive disorder. Asian J Psychiatr. 2014; 8: 26-32.
21. Vinckier F, Gourion D, Mouchabac S. Anhedonia predicts poor psychosocial functioning: results from a large cohort of patients treated for major depressive disorder by general practitioners. Eur Psychiatry. 2017; 44: 1-8.
22. Chen J, Xie S. Agomelatine versus paroxetine in treating depressive and anxiety symptoms in patients with chronic kidney disease. Neuropsychiatr Dis Treat. 2018; 14: 547-52.
23. Freiesleben SD, Furczyk K. A systematic review of agomelatine-induced liver injury. J Mol Psychiatry. 2015; 3: 4.
24. Drug safety update, Medicines and Healthcare products Regulatory Agency: Agomelatine (Valdoxan/Thymanax): risk of dose-related hepatotoxicity and liver failure – update warnings and monitoring guidance.
25. Perlemuter G, Cacoub P, Valla D et al. Characterisation of agomelatine-induced increase in liver enzymes: frequency and risk factors determined from a pooled analysis of 7605 treated patients. CNS Drugs. 2016; 30: 877-88.
26. Friedrich ME, Akimova E, Huf W et al. Drug-Induced Liver Injury during Antidepressant Treatment: Results of AMSP, a Drug Surveillance Program. Int J Neuropsychopharmacol. 2016; 19(4): pyv126. http://doi.org/10.1093/ijnp/pyv126.
27. Billioti de Gage S, Collin C, Le-Tri T et al. Antidepressants and Hepatotoxicity: A Cohort Study among 5 Million Individuals Registered in the French National Health Insurance Database. CNS Drugs. 2018; 32(7): 673-84.
28. Pladevall-Vila M, Pottegård A, Schink T et al. Risk of Acute Liver Injury in Agomelatine and Other Antidepressant Users in Four European Countries: A Cohort and Nested Case-Control Study Using Automated Health Data Sources. CNS Drugs. 2019; 33(4): 383-95.
29. 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: 616-26.
30. Montastruc F, Scotto S, Vaz IR et al. Hepatotoxicity related to agomelatine and other new antidepressants: a case/noncase approach with information from the Portuguese, French, Spanish, and Italian pharmacovigilance systems. J Clin Psychopharmacol. 2014; 34: 327-30.
31. Calabrese JR, Guelfi JD, Perdrizet-Chevallier C; Agomelatine Bipolar Study Group. Agomelatine adjunctive therapy for acute bipolar depression: preliminary open data. Bipolar Disord. 2007; 9: 628-35.
32. Baxter K, Preston CL (ed). Stockley’s Drug Interactions. Pocket Companion. 9th ed. Pharmaceutical Press 2010.
33. Siwek M, Wasik A. Agomelatyna – właściwości farmakologiczne i zastosowanie w psychiatrii. Psychiatr Psychol Klin. 2019; 19(2): 188-203.