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Approaches to therapy for depressions in neurology: prospects for the use of agomelatine

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This review provides information on prospects for using the antidepressant agomelatine in neurological practice. The drug has a unique receptor profile, being a melatonin receptor type 1 and 2 agonist and a serotonin receptor subtype 2C antagonist. Due to this and in addition to antidepressant action, the drug has a number of other effects, such as analgesic, anti-apathetic, anti-asthenic, procognitive, anxiolytic, and sleep-normalizing ones, which are of great importance in the treatment of neurological diseases. There are clinical and experimental data that prove the high efficiency and safety of agomelatin in the follow-up of patients with post-stroke depression, Parkinson’s disease, Alzheimer’s disease, Pick’s disease, Huntington’s disease, chronic fatigue syndrome, and pain syndromes.

About the Authors

D. V. Romanov
I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia; Mental Health Research Center
Russian Federation

Department of Psychiatry and Psychosomatics, Faculty of General Medicine.

8, Trubetskaya St., Build. 2, Moscow 119991; 34, Kashirskoe Shosse, Moscow 115552

B. A. Volel
I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia; Mental Health Research Center
Russian Federation

Beatrice Albertovna Volel - Department of Psychiatry and Psychosomatics, Faculty of General Medicine.

8, Trubetskaya St., Build. 2, Moscow 119991; 34, Kashirskoe Shosse, Moscow 115552

D. S. Petelin
I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia; Mental Health Research Center
Russian Federation

Department of Psychiatry and Psychosomatics, Faculty of General Medicine.

8, Trubetskaya St., Build. 2, Moscow 119991; 34, Kashirskoe Shosse, Moscow 115552


1. Kanner AM, editor. Depression in Neurologic Disorders: Diagnosis and Management. Wiley-Blackwell; 2012.

2. Voznesenskaya TG. Depressions in neurologic practice. Trudnyi patsient. 2003; 1(2): 26-30 (In Russ.).

3. Golovacheva VA, Parfenov VA. Depressions in neurologic practice: prevalence, diagnosis, stan-darts of treatment and new opportunities of pharmacotherapy. Meditsinskiisovet. 2015; (5):55-9. (In Russ.).

4. Damulin IV. Pecularities of depressions in neurological practice. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova 2005;(10):55-6. (In Russ.).

5. Romanov DV, Petelin DS, Volel' BA. Depressions in neurological practice. Meditsinskiisovet. 2018;(1):38-45. (In Russ.).

6. Rickards H. Depression in neurological disorders: Parkinson's disease, multiple sclerosis, and stroke J Neurol Neurosurg Psychiatry. 2005 Mar;76 Suppl 1:i48-52. doi: 10.1136/jnnp.2004.060426

7. Rickards H. Depression in neurological disorders: an update. Curr Opin Psychiatry. 2006 May; 19(3):294-8. doi: 10.1097/01.yco.0000218601.17722.5b

8. Yakhno NN, Nodel' MR. Pecularities of depressions in Parkinson's disease. 2013;(5):50-4. (In Russ.).

9. Williams L. Depression and stroke: cause or consequence? Semin Neurol. 2005 Dec;25(4): 396-409.

10. Ohira T, Iso H, Satoh S, et al. Prospective study of depressive symptoms and risk of stroke among Japanese. Stroke. 2001 Apr;32(4):903-8.

11. Lara E, Haro JM, Tang MX, et al. Exploring the excess mortality due to depressive symptoms in a community-based sample: The role of Alzheimer's Disease. J Affect Disord. 2016 Sep 15;202:163-70. doi: 10.1016/j.jad.2016.05.057. Epub 2016 May 27.

12. Sheng J, Liu S, Wang Y. The Link between Depression and Chronic Pain: Neural Mechanisms in the Brain. Neural Plasticity. 2017, Article ID 9724371, 10 pages. doi: 10.1155/2017/9724371

13. Yakhno NN, Kukushkin ML. Dysfunctional mechanism of chronic pain. Rossiiskii zhurnal boli. 2014;(1):23-4. (In Russ.).

14. Song TJ, Cho SJ, Kim WJ, et al. Anxiety and Depression in Tension-Type Headache: A Population-Based Study. PLoS One. 2016 Oct 26;11(10):e0165316. doi: 10.1371/journal.pone.0165316.eCollection2016.

15. Sullivan MJ, Reesor K, Mikail S, Fisher R. The treatment of depression in chronic low back pain: review and recommendations. Pain. 1992 Jul;50(1):5-13.

16. Golubev VL, Levin YaI, Vein AM. Bolezn' Parkinsona i sindrom parkinsonizma [Parkinson's disease and Parkinson's syndrome]. Moscow: MEDpress Inform; 2004. 416 p.

17. Smulevich AB, Romanov DV, Damulin IV. Differential diagnosis of mental disorders in neurologic practice. Psihicheskie raastroistva v obschey meditcine. 2018; 2: 4-10 (In Russ).

18. Sneed JR, Culang-Reinlieb ME. The vascular depression hypothesis: an update. Am J GeriatrPsychiatry. 2011 Feb;19(2):99-103.

19. Zakharov VV. Depressions in vascular diseases of brain. Effektivnaya farmakoterapiya. Nevrologiya. 2014;(3):4-11. (In Russ.).

20. Савина МА. Постинсультная депрессия. Журнал неврологии и психиатрии им. С.С. Корсакова. 2005;105(7):67-76. [Savina MA. Post-stroke depression. Zhurnal nevrologii ipsikhiatrii im. S.S. Korsakova. 2005;105(7):67-76. (In Russ.)].

21. Di Maio L, Squitieri F, Napolitano G, et al. Onset symptoms in 510 patients with Huntington's disease. J Med Genet. 1993 Apr; 30(4):289-92.

22. Carson AJ, Postma K, Stone J, et al. The outcome of depressive disorders in neurology patients: a prospective cohort study J Neurol Neurosurg Psychiatry. 2003 Jul;74(7):893-6. doi: 10.1136/jnnp.74.7.893

23. American Psychiatric Associaion. Major depressive disorder: practice guideline. APA guidelines; 2010.

24. National Institute for health and care exel-lance. Depression in adults: recognition and management. NICE guideline; 2016.

25. Cleare A, Pariante C, Young A, et al. Evidence-based guidelines for treating depressive disorders with antidepressants: A revision of the 2008 British Association for Psychopharmacology guidelines. J Psychopharmacol. 2015 May;29(5):459-525. doi: 10.1177/0269881115581093. Epub 2015 May 12.

26. Price A, Rayner L, Okon-Rocha E, et al. Antidepressants for the treatment of depression in neurological disorders: a systematic review and meta-analysis of randomised controlled trials. J Neurol Neurosurg Psychiatry. 2011 Aug; 82(8):914-23. doi: 10.1136/jnnp.2010.230862. Epub 2011 May 10.

27. Jakobsen JC, Katakam KK, Schou A, et al. Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and Trial Sequential Analysis. BMC Psychiatry. 2017 Feb 8;17(1):58. doi: 10.1186/s12888-016-1173-2.

28. Schatzberg AF, Cole JO, DeBattista C. Manual of clinical psychopharmacology. Washington: American Psychiatric Pub; 2010. 437 p.

29. Kostev K, Rex J, Eith T, Heilmaier C. Which adverse effects influence the dropout rate in selective serotonin reuptake inhibitor (SSRI) treatment? Results for 50,824 patients. Ger Med Sci. 2014 Oct 16;12:Doc15. doi: 10.3205/000200.eCollection2014.

30. Machado M, Iskedjian M, Ruiz I, Einarson TR. Remission, dropouts, and adverse drug reaction rates in major depressive disorder: a meta-analysis of head-to-head trials. Curr Med Res Opin. 2006 Sep;22(9):1825-37.

31. Hemeryck A, Belpaire FM. Selective serotonin reuptake inhibitors and cytochrome P-450 mediated drug-drug interactions: an update. Curr Drug Metab. 2002 Feb;3(1):13-37.

32. Hanoun N, Mocaer E, Boyer PA, et al. Differential effects of the novel antidepressant agomelatine (S 20098) versus fluoxetine on 5-HT1A receptors in the rat brain. Neuropharmacology. 2004 Sep;47(4):515-26.

33. Fornaro M, Prestia D, Colicchio A, et al. A Systematic, Updated Review on the Antidepressant Agomelatine Focusing on its Melatonergic Modulation. CurrNeuropharmacol. 2010 Sep;8(3): 287-304. doi: 10.2174/157015910792246227.

34. De Berardis D, Marini S, Fornaro M, et al. The Melatonergic System in Mood and Anxiety Disorders and the Role of Agomelatine: Implications for Clinical Practice. Int J Mol Sci. 2013 Jun 13;14(6):12458-83. doi: 10.3390/ijms140612458.

35. Emet M, Ozcan H, Ozel L, et al. A Review of Melatonin, Its Receptors and Drugs. Eurasian J Med. 2016 Jun;48(2):135-41. doi: 10.5152/eurasianjmed.2015.0267.

36. Eliwa H, Belzung C, Surget A. Adult hippocampal neurogenesis: Is it the alpha and omega of antidepressant action? Biochem Pharmacol. 2017 Oct 1;141:86-99. doi: 10.1016/j.bcp.2017.08.005. Epub 2017 Aug 8.

37. Larson J, Jessen RE, Uz T, et al. Impaired hippocampal long-term potentiation in melatonin MT2 receptor-deficient mice. Neurosci Lett. 2006 Jan 23;393(1):23-6. Epub 2005 Oct 3.

38. Pappolla MA, Sos M, Omar RA, et al. Melatonin prevents death of neuroblastoma cells exposed to the Alzheimer amyloid peptide. J Neurosci. 1997 Mar 1;17(5):1683-90.

39. Wang XC, Zhang J, Yu X, et al. Prevention of isoproterenol-induced tau hyperphosphorylation by melatonin in the rat. Sheng Li Xue Bao. 2005 Feb 25;57(1):7-12.

40. Comai S, Gobbi G. Unveiling the role of melatonin MT2 receptors in sleep, anxiety and other neuropsychiatric diseases: a novel target in psychopharmacology. J Psychiatry Neurosci. 2014 Jan;39(1):6-21. doi: 10.1503/jpn.130009.

41. Yu C, Wu G, Xu S, et al. Effect of melatonin on release of beta-endorphin, norepinephrine and 5-hydroxytryptamine in rat brain. Yao Xue Xue Bao. 2001 Jan;36(1):5-9.

42. Millan MJ, Gobert A, Lejeune F, et al. The novel melatonin agonist agomelatine (S20098) is an antagonist at 5-hydroxytrypta-mine2C receptors, blockade of which enhances the activity of frontocortical dopaminergic and adrenergic pathways. J Pharmacol Exp Ther. 2003 Sep;306(3):954-64. Epub 2003 May 15.

43. Berg KA, Harvey JA, Spampinato U, et al. Physiological relevance of constitutive activity of 5-HT2A and 5-HT2C receptors. Trends Pharmacol Sci. 2005 Dec;26(12):625-30. Epub 2005 Nov 2.

44. Aydin TH, Can O D, Demir O zkay U, et al. Effect of subacute agomelatine treatment on painful diabetic neuropathy: involvement of cat-echolaminergic mechanisms. Fundam Clin Pharmacol. 2016 Dec;30(6):549-567. doi: 10.1111/fcp.12224. Epub 2016 Oct 5.

45. De Berardis D, Acciavatti T, di Iorio G, et al. The melatonergic system: Effects on sleep and implications for the treatment of psychiatric disorders. ChronoPhysiol Ther. 2011;(1): 59-67. doi: 10.2147/CPT.S16972

46. Poissonnet G, Parmentier JG, Boutin JA, et al. The emergence of selective 5-HT 2B antagonists structures, activities and potential therapeutic applications. Mini Rev Med Chem. 2004 Mar;4(3):325-30.

47. Guglielmo R, Martinotti G, Di Giann-antonio M, et al. A possible new option for migraine management: agomelatine. Clin Neuropharmacol. 2013 Mar-Apr;36(2):65-7. doi: 10.1097/WNF.0b013e3182800271.

48. Kamal M, Gbahou F, Guillaume J, et al. Convergence of melatonin and 5-HT signaling at MT2/5-HT2C receptor heteromers. J Biol Chem. 2015 May 1;290(18):11537-46. doi: 10.1074/jbc.M114.559542. Epub 2015 Mar 13.

49. Tardito D, Molteni R, Popoli M, et al. Synergistic mechanisms involved in the antidepressant effects of agomelatine. Eur Neuropsychopharmacol. 2012;22 Suppl 3:S482-6. Epub 2012 Aug 4.

50. Guaiana G, Gupta S, Chiodo D, et al. Agomelatine versus other antidepressive agents for major depression. Cochrane Database Syst Rev. 2013 Dec 17;(12):CD008851. doi: 10.1002/14651858.CD008851.pub2.

51. Cipriani A, Furukawa T, Salanti G, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet. 2018 Apr 7;391(10128):1357-1366. doi: 10.1016/S0140-6736(17)32802-7. Epub 2018 Feb 21.

52. Howland R. Critical appraisal and update on the clinical utility of agomelatine, a melatonergic agonist, for the treatment of major depressive disease in adults. Neuropsychiatr Dis Treat. 2009;5:563-76. Epub 2009 Nov 16.

53. Wong A, Lee C, Lee J. Agomelatine overdose and related toxicity. Toxicology Communications. 2018 Jan;2(1):62-5. doi: 10.1080/24734306.2018.1503850

54. Freiesleben SD, Furczyk K. A systematic review of agomelatine-induced liver injury. J Mol Psychiatry. 2015 Apr 21;3(1):4. doi: 10.1186/s40303-015-0011-7.eCollection 2015.

55. Biliotti de Gage S, Colin C, Le Tri T, et al. Hepatotoxicity of agomelatine and other antidepressants versus selective serotonin reuptake inhibitors. Programme of the 30th ECNP Congress. Paris; 2017. P.2.e.007

56. Dubocovich ML. Drug evaluation: Agomelatine targets a range of major depressive disorder symptoms. Curr Opin Investig Drugs. 2006 Jul;7(7):670-80.

57. Vimala P, Bhutada P, Patel F. Therapeutic potential of agomelatine in epilepsy and epileptic complications. Med Hypotheses. 2014 Jan; 82(1):105-10. doi: 10.1016/j.mehy.2013.11.017. Epub 2013 Nov 21.

58. Yakhno NN, Voznesenskaya TG. Effectiveness and tolerability of agomelatine in treatment of mild and moderate depressions in neriligical practice (results of Russian multicentral study «Camertone». Nevrologicheskii zhur-nal. 2012;17(1):43-9. (In Russ.).

59. Vorobieva OV. Valdoxan in the treatment of depression in neurological practice: results of the Russian multicenter naturalistic study «Resonance». Zhurnal nevrologii ipsikhiatrii im. S.S. Korsakova. 2012; 112(9):47-51. (In Russ.).

60. Bogolepova AM, Chukanova EI, Smirnova KV, et al. The experience of the use of valdoxan in the therapy of post-stroke depression. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2011;111(4): 42-6. (In Russ.).

61. Gerdt AM, Gubareva EA, Kramarchuk MV, et al. Effectiveness and safety of the drug Valdoxane in patients with post-stroke depression. Psikhiatriya ipsikhofarmakoterapiya im. P.B. Gannushkina. 2011;(6):22-6. (In Russ.).

62. Khasanova DR, Zhitkova YuV, Safiullina AA. Efficacy of valdoxan in the prevention and treatment of post-stroke depression. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2012;4(3):48-53. (In Russ.). doi: 10.14412/2074-2711-2012-403

63. Kusnetsov VV. Melatoninergic Antidepressant in Post-Stroke Depression. Therapy Advances in Aging Research. 2018;(7):29-38. doi: 10.4236/aar.2018.72003

64. Artemov AN, Vasilenko IV, Trif YuV, et al. The experience of the use of Valdoxan in the treatment of anxiety-depressive disorders in post-stroke patients in the early recovery period. Psikhicheskie rasstroistva v obshchei meditsine. 2011;(1):42-5. (In Russ.).

65. Avila A, Cardona X, Martin-Baranera M. Agomelatine for Depression in Parkinson Disease Additional Effect on Sleep and Motor Dysfunction. J Clin Psychopharmacol. 2015 Dec;35(6):719-23. doi: 10.1097/JCP.0000000000000404.

66. De Berardis D, Fornaro M, Serroni N, et al. Agomelatine treatment of major depressive disorder in parkinson's disease: a case series. J Neuropsychiatry Clin Neurosci. 2013 Fall;25(4): 343-5. doi: 10.1176/appi.neuropsych.12110286.

67. Gustov AV, Aleksandrova EA, Parshina EV, et al. Optimization approach to therapy and psycho-emotional disorders and dyssomnia in Parkinson's disease. Psikhicheskie rasstroistva v obshchei meditsine. 2015;(2-3): 54-8. (In Russ.).

68. Golubev VL, Pilipovich AA, Goitemirova PU. Depression and sleep disorders in Parkinson's Disease: role of valdoxan in treatment. Psikhicheskie rasstroistva v obshchei meditsine. 2014;(1):51-5. (In Russ.).

69. Harrison F, Aerts L, Brodaty H. Apathy in Dementia: Systematic Review of Recent Evidence on Pharmacological Treatments. Curr Psychiatry Rep. 2016 Nov;18(11):103.

70. Callegari I, Mattei C, Benassi F, et al. Agomelatine Improves Apathy in Frontotemporal Dementia. Neurodegener Dis. 2016;16 (5-6):352-6. doi: 10.1159/000445873. Epub 2016 May 27.

71. Karaiskos D, Pappa E, Katirtzoglou E. Agomelatine for treating apathy in alzheimer's disease. European Psychiatry. 2014;29(1):1. doi: 10.1016/S0924-9338(14)78444-5

72. Pardini M, Cordano C, Benassi F, et al. Agomelatine but not melatonin improves fatigue perception: a longitudinal proof-of-concept study. Eur Neuropsychopharmacol. 2014 Jun; 24(6):939-44. doi: 10.1016/j.euroneuro.2014.02.010. Epub 2014 Feb 25.

73. Altinyazar V, Kiylioglu N. Insomnia and dementia: is agomelatine treatment helpful? Case report and review of the literature. Ther Adv Psychopharmacol. 2016 Aug;6(4):263-8. doi: 10.1177/2045125316646064. Epub 2016 May 16.

74. O'Neill B, Gardani M, Findlay G, et al. Challenging behaviour and sleep cycle disorder following brain injury: a preliminary response to agomelatine treatment. Brain Inj. 2014;28(3): 378-81. doi: 10.3109/02699052.2013.865264. Epub 2013 Dec 30.

75. Tabeeva GR, Sergeev AV, Gromova SA. Possibilities of preventive treatment of migraine with the MT1- and MT2 agonist and 5-HT2c-receptor antagonist agome-latin (valdoxan). Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2011;Ш(9):32-6. (In Russ.).

76. Plasencia-Garcia BO, Romero-Guillena SL, Quiros-Lopez A, et al. Agomelatine and migraine management: a successfully treated case series. Ther Adv Psychopharmacol. 2015 Aug;5(4):243-5. doi: 10.1177/2045125315584869.

77. D’Amato CC, Pizza V, Marmolo T, et al. Fluoxetine for migraine prophylaxis: a doubleblind trial. Headache. 1999 Nov-Dec;39(10): 716-9.

78. 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 Mar;47(2):67-72. doi: 10.1055/s-0033-1363659. Epub 2014 Feb 18.

79. Bruno A, Mico U, Lorusso S, et al. Agomelatine in the treatment of fibromyalgia: A 12-week, open-label, uncontrolled preliminary study. JClin Psychopharmacol. 2013 Aug;33(4): 507-11. doi: 10.1097/JCP.0b013e31829057ae.

80. M'Dahoma S, Poitevin M, Dabala E. α2- and β2-Adrenoreceptor-Mediated Efficacy of the Atypical Antidepressant Agomelatine Combined With Gabapentin to Suppress Allodynia in Neuropathic Rats With Ligated Infraorbital or Sciatic Nerve. Front Pharmacol. 2018 Jun 7;9:587. doi: 10.3389/fphar.2018.00587.eCollection 2018.

81. Gupta S, Sharma B. Pharmacological benefits of agomelatine and vanillin in experimental model of Huntington's disease. Pharmacol Biochem Behav. 2014 Jul;122:122-35. doi: 10.1016/j.pbb.2014.03.022. Epub 2014 Apr 3.


For citations:

Romanov D.V., Volel B.A., Petelin D.S. Approaches to therapy for depressions in neurology: prospects for the use of agomelatine. Neurology, Neuropsychiatry, Psychosomatics. 2018;10(4):101-110. (In Russ.)

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