Effectiveness and tolerability of agomelatine (Valdoxan) in the treatment of depression after COVID-19 (TELESFOR study)

Medvedev V.E.; Bogolepova A.N.

doi:https://doi.org/10.17116/jnevro202512509190

OBJECTIVE

To study the antidepressant efficacy and the tolerability of agomelatine (Valdoxan) in daily clinical practice in patients with a depressive episode that occurred after COVID-19.

MATERIAL AND METHODS

The final analysis included 103 patients (70.9% women, average age 45 years). Of these, 78.6% have had mild COVID-19 in the last 3 months, and 21.4% have had moderate COVID-19. The average time from the onset of infection to inclusion in the study was 2.1±0.7 months. At the start of the study, 53.4% of patients had a mild depressive episode, and 46.6% had a moderate depressive episode. Clinical and psychopathological, psychometric (HAMD-17, CGI, SF-36), and statistical methods of investigation were used.

RESULTS

A significant decrease in the severity of depression was revealed. The average overall score on the HAMD-17 scale decreased compared to baseline by 2.6±3.3, 6.7±5.3, and 10.9±4.9 at weeks 2, 4, and 8 of agomelatin administration, respectively (p<0.0001). Mental and physical indicators on the SF-36 scale also significantly improved compared to baseline (p<0.0001). By the end of the study, 81.4% of patients had responded to therapy, 71.6% had achieved remission according to the criteria established in the study. It was found that the initial value of the total HAMD-17 score has a statistically significant effect (p<0.0001) on the outcome of depression therapy after COVID-19, an additional contribution is made by the prescription of COVID-19 disease. Agomelatin was well tolerated during the 8 weeks of follow-up.

CONCLUSION

The results indicate a high antidepressant and anxiolytic effectiveness and safety of agomelatine after 8 week of treatment of patients with depression after COVID-19 infection. The results of the study add to the knowledge about the antidepressant effectiveness of agomelatine and suggest that it may become a drug for the treatment of MDE in patients who have suffered COVID-19 infection.

Keywords:

agomelatine

depression

quality of life

COVID-19

effectiveness

tolerability

Authors:

Medvedev V.E.

Peoples’ Friendship University of Russia named after Patrice Lumumba

SPIN RSCI: 2814-4975
Scopus AuthorID: 55545252400
ResearcherID: AAH-1849-2020
ORCID: 0000-0001-8653-596X

Bogolepova A.N.

Federal Center of Brain Research and Neurotechnologies of the Federal Medical Biological Agency;
Pirogov Russian National Research Medical University

SPIN RSCI: 6775-0279
Scopus AuthorID: 6602240836
ORCID: 0000-0002-6327-3546

Received:

14.08.2025

Accepted:

22.08.2025

Close metadata

References:

Wiersinga WJ, Rhodes A, Cheng AC, et al. Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review. JAMA. 2020;324(8):782-793. https://doi.org/10.1001/jama.2020.12839
Gupta A, Madhavan MV, Sehgal K, et al. Extrapulmonary manifestations of COVID-19. Nat Med. 2020;26(7):1017-1032. https://doi.org/10.1038/s41591-020-0968-3
Khraisat B, Toubasi A, AlZoubi L, et al. Meta-analysis of prevalence: the psychological sequelae among COVID-19 survivors. Int J Psychiatry ClinPract. 2022;26(3):234-243. https://doi.org/10.1080/13651501.2021.1993924
Kotova OV, Poluektov MG, Medvedev VE, et al. Sleep disorders in post-covid syndrome — a problem of psychiatry or neurology? S.S. Korsakov Journal of Neurology and Psychiatry. 2022;122(5-2):23-28. (In Russ.). https://doi.org/10.17116/jnevro202212205223
Medvedev VE. Anxiety-depressive spectrum disorders on the background of COVID-19: treatment options. Neurology, neuropsychiatry, psychosomatics. 2021;13(2):111-116. (In Russ.). https://doi.org/10.14412/2074-2711-2021-2-111-116
Kotova OV, Zuikova NL, Palin AV, et al. Psychopathological disorders in chronic cerebral ischemia: possibilities of prevention. The attending physician. 2021;5(24):22-26. (In Russ.). https://doi.org/10.51793/OS.2021.15.98.005
Schou TM, Joca S, Wegener G, et al. Psychiatric and neuropsychiatric sequelae of COVID-19 — A systematic review. Brain Behav Immun. 2021;97:328-348. https://doi.org/10.1016/j.bbi.2021.07.018
Huang C, Huang L, Wang Y, et al. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet. 2023;401(10393):e21-e33. https://doi.org/10.1016/S0140-6736(23)00810-3
Avedisova AS, Zakharova KV, Marachev MP. Results of the JAZZ observational program: «The effectiveness of the drug agomelatine (Valdoxan) in the treatment of patients with anxiety depression in the framework of major depressive disorder. Psychiatry and psychopharmacotherapy. 2013;6:14-22. (In Russ.).
Medvedev VE. Efficacy and tolerability of modern antidepressants: results of network meta-analyses and Russian experience. S.S. Korsakov Journal of Neurology and Psychiatry. 2018;118(11):109-117. (In Russ.). https://doi.org/10.17116/jnevro2018118111109
Medvedev VE. Agomelatine in the treatment of mild-to-moderate depression in patients with cardiovascular disorders: results of the National Multicenter Observational Study PULSE. Neuropsychiatric disease and treatment. 2017;13:1141-1151.
Medvedev VE, Korovyakova EA, Frolova VI, et al. Antidepressant therapy in patients with cardiovascular diseases. Neurology, neuropsychiatry and psychosomatics. 2019;11(1):131-140. (In Russ.). https://doi.org/10.14412/2074-2711-2019-1-131-140
Volel BA. Safety and efficacy of Valdoxan for the treatment of anxiety and depressive disorders in clinical practice (based on the results of the OCTAVE protocol). Psychiatry and psychopharmacotherapy. 2015;17(2):9-14. (In Russ.).
Rogers JP, Chesney E, Oliver D, et al. Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic. Lancet Psychiatry. 2020;7(7):611-627. https://doi.org/10.1016/S2215-0366(20)30203-0
Renaud-Charest O, Lui L, Eskander S, et al. Onset and frequency of depression in post-COVID-19 syndrome: a systematic review. J Psychiatr Res. 2021;144:129-137.
Medvedev VE, Dogotar OA. COVID-19 and mental health: challenges and first conclusions. Neurology, neuropsychiatry, psychosomatics. 2020;12(6):4-10. (In Russ.). https://doi.org/10.14412/2074-2711-2020-6-4-10
Kotova OV, Medvedev VE, Akarachkova ES, et al. Covid-19 and stress-related disorders. S.S. Korsakov Journal of Neurology and Psychiatry. Special editions. 2021;121(5-2):122-128. (In Russ.). https://doi.org/10.17116/jnevro2021121052122
Kotova OV, Artemenko AR, Belyaev AA, et al. Respiratory panic attacks and COVID-19. Practical medicine. 2021;19(1):29-33. (In Russ.). https://doi.org/10.32000/2072-1757-2021-1-29-33
Asmundson GJG, Taylor S. Coronaphobia: Fearandthe 2019-nCoVoutbreak. J AnxietyDisord. 2020;70:102196. https://doi.org/10.1016/j.janxdis.2020.102196
Medvedev VE, Dogotar OA, Lyzlova NY. The impact of work and study in a pandemic on the mental state of medical specialists. Neurology, neuropsychiatry, psychosomatics. 2022;14(5):36-42. (In Russ.). https://doi.org/10.14412/2074-2711-2022-5-36-42
Medvedev VE, Frolova VI, Gushanskaya EV, et al. Asthenic disorders in the framework of postcovid syndrome. S.S. Korsakov Journal of Neurology and Psychiatry. 2021;121(4):152-158. (In Russ.). https://doi.org/10.17116/jnevro2021121041152
Medvedev VE. Anxiety-depressive spectrum disorders on the background of COVID-19: treatment options. Neurology, neuropsychiatry, psychosomatics. 2021;13(2):111-116. (In Russ.). https://doi.org/10.14412/2074-2711-2021-2-111-116
Pashaei Y. Drug repurposing of selective serotonin reuptake inhibitors: Could these drugs help fight COVID-19 and save lives? J Clin Neurosci. 2021;88:163-172. https://doi.org/10.1016/j.jocn.2021.03.010
Hoertel N, Sánchez-Rico M, Vernet R, et al. Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: Results from an observational study. Mol Psychiatry. 2021;10:1-14. https://doi.org/10.1038/s41380-021-01021-4
Dąbrowska E, Galińska-Skok B, Waszkiewicz N. Depressive and Neurocognitive Disorders in the Context of the Inflammatory Background of COVID-19. Life (Basel). 2021;11(10):1056. https://doi.org/10.3390/life11101056
Lenze EJ, Mattar C, Zorumski CF, et al. Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients with Symptomatic COVID-19: A Randomized Clinical Trial. JAMA. 2020;324(22):2292-2300. https://doi.org/10.1001/jama.2020.22760
Boretti A. Effectiveness of fluvoxamine at preventing COVID-19 infection from turning severe. EurNeuropsychopharmacol. 2023;67:83-85. https://doi.org/10.1016/j.euroneuro.2022.12.001
Dobrodeeva V, Abdyrahmanova A, Astafeva D, et al. Pharmacogenetic aspects of COVID-19 management and post-COVID-19 depression treatment with fluvoxamine. Psychiatr Danub. 2022;34(Suppl 8):25-30.
Mazza MG, Zanardi R, Palladini M, et al. Rapid response to selective serotonin reuptake inhibitors in post-COVID depression. EurNeuropsychopharmacol. 2022;54:1-6. https://doi.org/10.1016/j.euroneuro.2021.09.009
Di Nicola M, Pepe M, Montanari S, et al. Vortioxetine improves physical and cognitive symptoms in patients with post-COVID-19 major depressive episodes. EurNeuropsychopharmacol. 2023;70:21-28. https://doi.org/10.1016/j.euroneuro.2023.02.006
Medvedev VE, Retyunsky KYu, Ovchinnikov AA, et al. Differences in the assessment of the severity of depression by doctors and patients in the course of combination therapy with agomelatine (multicenter study «EMOTION»). S.S. Korsakov Journal of Neurology and Psychiatry. 2016;11:26-34. (In Russ.). https://doi.org/10.17116/jnevro201611611126-34
Olié JP, Kasper S. Efficacy of agomelatine, a MT1/MT2 receptor agonist with 5-HT2C antagonistic properties, in major depressive disorder. Int J Neuropsychopharmacol. 2007;10(5):661-673. https://doi.org/10.1017/S1461145707007766
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):109-120. https://doi.org/10.4088/JCP.09m05347blu
Lemoine P, 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(11):1723-1732. https://doi.org/10.4088/jcp.v68n1112
Quera-Salva MA, Hajak G, Philip P, et al. Comparison of agomelatine and escitalopram on nighttime sleep and daytime condition and efficacy in major depressive disorder patients. Int Clin Psychopharmacol. 2011;26(5):252-262.
Medvedev VE, Bogolepova AN, Morozov DP, et al. Antidepressant and anti-anxiety efficacy and tolerability of agomelatine in the treatment of depression after COVID-19 in daily clinical practice (non-interventional TELESPHOR study). Neurology, neuropsychiatry, psychosomatics. 2024;16(6):61-70. (In Russ.). https://doi.org/10.14412/2074-2711-2024-6-61-70
Medvedev VE, Ter-Israelyan AYu, Frolova VI, et al. The experience of using valdoxan in depression with cognitive impairment. S.S. Korsakov Journal of Neurology and Psychiatry. 2018;2:77-80. (In Russ.).
Medvedev VE. Efficacy and tolerability of modern antidepressants: results of network meta-analyses and Russian experience. S.S. Korsakov Journal of Neurology and Psychiatry. 2018;118(11):109-117. (In Russ.). https://doi.org/10.17116/jnevro2018118111109
Medvedev VE, Frolova VI, Ter-Israelyan AYu, et al. Therapy of depressive disorders with circadian rhythms. Psychiatry and psychopharmacotherapy. 2018;20(5):38-43. (In Russ.).
de Bodinat C, Guardiola-Lemaitre B, Mocaer E, et al. Agomelatine, the first melatonergic antidepressant: discovery, characterization and development. Nat Rev Drug Discov. 2010;9:628-642. https://doi.org/10.1038/nrd3140
Taylor D, Sparshatt A, Varma S, et al. Antidepressant efficacy of agomelatine: meta-analysis of published and unpublished studies. BMJ. 2014;348:g1888. https://doi.org/10.1136/bmj.g1888
Cipriani A, Furukawa TA, 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;391(10128):1357-1366. https://doi.org/10.1016/S0140-6736(17)32802-7
Demyttenaere K, Corruble E, Hale A, et al. A pooled analysis of six-month comparative efficacy and tolerability in four randomized clinical trials: agomelatine versus escitalopram, fluoxetine, and sertraline. CNS Spectra. 2013;18:163-170. https://doi.org/10.1017/S1092852913000060
Kennedy SH, Rizvi SJ. Agomelatine in the treatment of major depressive disorder: potential for clinical effectiveness. CNS Drugs. 2010;24:479-499. https://doi.org/10.2165/11534420-000000000-00000
Kennedy SH, Avedisova A, Belaidi 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;26:378-389. https://doi.org/10.1016/j.euroneuro.2015.09.006
Ivanov SV. Valdoxan (agomelatine) in the treatment of moderate and severe depression of non-psychotic level in outpatient and hospital practice (results of the Russian multicenter study «CHRONOS»). Psychiatry and psychopharmacotherapy. 2009;6:14-17. (In Russ.).
Smulevich AB, Andryushchenko AV, Beskova DA. Therapy of non-psychotic depression with the antidepressant agomelatine (Valdoxan): the results of the observational multicenter study «RHYTHM». Psychiatry and psychopharmacotherapy. 2010;12(4):4-11. (In Russ.).
Vorobyeva OV. Valdoxane in the treatment of depression in neurological practice: results of the Russian multicenter naturalistic study «Resonance». S.S. Korsakov Journal of Neurology and Psychiatry. 2012;112(9):47-51. (In Russ.).
Tsygankov BD, Yaltonskaya AV, Filippskikh SV. Valdoxan (Agomelatine) in the treatment of severe and moderate nonpsychotic depression (results of an observational study). Review of Psychiatry and Medical Psychology. Bekhtereva. 2011;1:37-40. (In Russ.).
Yakhno NN. Voznesenskaya T.G. Efficacy and tolerability of agomelatine (Valdoxan) in the treatment of mild and moderate depressive disorders in neurological practice (results of the Russian multicenter study «Kamerton»). Neurological journal. 2012;17(1):43-49. (In Russ.).
Millan MJ. Agomelatine for the treatment of generalized anxiety disorder: focus on its distinctive mechanism of action. TherAdvPsychopharmacol. 2022;12:20451253221105128. https://doi.org/10.1177/20451253221105128
Gupta K, Gupta R, Bhatia MS, et al. Effect of Agomelatine and Fluoxetine on HAM-D Score, Serum Brain-Derived Neurotrophic Factor, and Tumor Necrosis Factor-α Level in Patients With Major Depressive Disorder With Severe Depression. J ClinPharmacol. 2017;57(12):1519-1526. https://doi.org/10.1002/jcph.963
Molteni R, Macchi F, Zecchillo C, et al. Modulation of the inflammatory response in rats chronically treated with the antidepressant agomelatine. EurNeuropsychopharmacol. 2013;23(11):1645-1655. https://doi.org/10.1016/j.euroneuro.2013.03.008
Hyeon JY, Choi EY, Choe SH, et al. Agomelatine, a MT1/MT2melatonergic receptor agonist with serotonin 5-HT2C receptor antagonistic properties, suppresses Prevotella intermedia lipopolysaccharide-induced production of proinflammatory mediators in murine macrophages. Arch Oral Biol. 2017;82:11-18. https://doi.org/10.1016/j.archoralbio.2017.05.015
Kalkman HO, Feuerbach D. Antidepressant therapies inhibit inflammation and microglial M1-polarization. PharmacolTher. 2016;163:82-93. https://doi.org/10.1016/j.pharmthera.2016.04.001
Mas M, García-Vicente JA, Estrada-Gelonch A, et al. Antidepressant Drugs and COVID-19: A Review of Basic and Clinical Evidence. J Clin Med. 2022;11(14):4038. https://doi.org/10.3390/jcm11144038
Morozov PV, Becker RA, Bykov YuV. On the possible role of some psychotropic drugs in COVID-19 therapy (a brief overview). Experimental and clinical pharmacology. 2021;84(2):104-112. (In Russ.). https://doi.org/10.30906/0869-2092-2021-84-2-104-112
Borovcanin MM, Vesic K, Balcioglu YH, et al. Prescription of selective serotonin reuptake inhibitors in COVID-19 infection needs caution. Front. Psychiatry. 2022;13:1052710. https://doi.org/10.3389/fpsyt.2022.1052710
Firouzabadi D. The effect of selective serotonin and norepinephrine reuptake inhibitors on clinical outcome of COVID‐19 patients: A systematic review and meta‐analysis. Health Sci Rep. 2022;5(6):e892. https://doi.org/10.1002/hsr2.892