Vortioxetine’s 10 years in Czech psychiatry – history of development and new findings
Authors:
Jan Hubeňák 1; Eva Kitzlerová 2; Martin Anders 2
Authors‘ workplace:
Psychiatrická klinika LF UK a FN Hradec Králové
1; Psychiatrická klinika 1. LF UK a VFN v Praze
2
Published in:
Čes. a slov. Psychiat., 121, 2025, No. 5, pp. 222-229.
Category:
Review
doi:
https://doi.org/10.48095/cccsp202521
Overview
Vortioxetine is a new multimodal antidepressant developed to improve tolerability, with rapid onset of effect, and to improve the lack of efficacy in some areas of depressive disorder such as residual symptoms, cognitive functions, and functional abilities. Vortioxetine has been evaluated in an impressive number of blinded, randomized, controlled trials as well as in open-label, short-term, and long-term studies. In most cases, it has been beneficial.
Keywords:
depression – vortioxetine – antidepressive agents – depressive disorder, major – depressive disorder, treatment-resistant
Sources
1. Anders M, Albrecht J. Nové antidepresivum s multimodálním mechanizmem účinku – vortioxetin (Lu-AA21004). Psychiatrie 2013; 17 (1): 35–42.
2. Mohr P, Anders M, Masopust J. Vortioxetin v léčbě depresivní poruchy a možnosti zlepšení kognitivních funkcí. Psychiatrie 2014; 18 (4): 206–211.
3. Češková E. Farmakologická léčba kognitivní dysfunkce u deprese. Psychiatrie pro praxi 2019; 20 (2): 64–68.
4. Mohr P, Melicher T, Knytl P. Vortioxetin: přehled nového antidepresiva. Psychiatrie pro praxi 2016; 17 (1): 31–34. doi: 10.36290/psy.2016.009.
5. Patarák M. Základná neuropsychofarmakológia vortioxetínu v prefrontálnej kôre a hipokampe. Psychiatrie 2016; 20 (4): 193–197.
6. Nutt DJ. Beyond psychoanaleptics – can we improve antidepressant drug nomenclature? J Psychopharmacol 2009; 23 (4): 343–345. doi: 10.1177/0269881109105498.
7. American Psychological Association. APA Dictionary of Psychology: Multifunctional antidepressant. [online]. 2018 [cit. 19. 9. 2025]. Dostupné z: https: //dictionary.apa.org/multifunctional-antidepressant.
8. Gibb A, Deeks ED. Vortioxetine: first global approval. Drugs 2014; 74 (1): 135–145. doi: 10.1007/s40265-013-0161-9.
9. Bang-Andersen B, Olsen CK, Sanchéz C. The discovery of the antidepressant vortioxetine and the research that uncovered its potential to treat the cognitive dysfunction associated with depression. In: Fischer J, Childers WE (eds.). Successful Drug Discovery. Weinheim: Wiley-VCH 2017 : 189–214.
10. Skolnick P. Antidepressants for the new millennium. Eur J Pharmacol 1999; 375 (1–3): 31–40. doi: 10.1016/S0014-2999 (99) 00330-1.
11. Gaynes BN, Warden D, Trivedi MH et al. What did STAR*D teach us? Results from a large-scale, practical, clinical trial for patients with depression. Psychiatr Serv 2009; 60 (11): 1439–1445. doi: 10.1176/ps.2009.60.11.1439.
12. Romero L, Bel N, Artigas F et al. Effect of pindolol on the function of pre - and postsynaptic 5-HT1A receptors: in vivo microdialysis and electrophysiological studies in the rat brain. Neuropsychopharmacology 1996; 15 (4): 349–360. doi: 10.1016/0893-133X (95) 00240-E.
13. Boothman LJ, Mitchell SN, Sharp T. Investigation of the SSRI augmentation properties of 5-HT2 receptor antagonists using in vivo microdialysis. Neuropharmacology 2006; 50 (6): 726–732. doi: 10.1016/j.neuropharm.2005.11.020.
14. Artigas F. Serotonin receptors involved in antidepressant effects. Pharmacol Ther 2013; 137 (1): 119–131. doi: 10.1016/j.pharmthera.2012.09.006.
15. Thase ME. US Food and Drug Administration’s review of the novel antidepressant vortioxetine. J Clin Psychiatry 2015; 76 (1): e120–121. doi: 10.4088/JCP.14com09609.
16. Christensen MC, McIntyre RS, Adair M et al. Clinical benefits of vortioxetine 20 mg/day in patients with major depressive disorder. CNS Spectr 2023; 28 (6): 693–701. doi: 10.1017/S1092852923002249.
17. McIntyre RS, Florea I, Pedersen MM et al. Head-to-head comparison of vortioxetine versus desvenlafaxine in patients with major depressive disorder with partial response to SSRI therapy: results of the VIVRE study. J Clin Psychiatry 2023; 84 (4): 23m14780. doi: 10.4088/JCP.23m14780.
18. Hochstrasser B, Hasler G, Baumann A et al. Effectiveness and tolerability of vortioxetine oral drops versus oral tablets in major depressive disorder: a real-world cohort study in Switzerland. CNS Drugs 2025. doi: 10.1007/s40263-025-01207-2.
19. Sheehan KH, Sheehan DV. Assessing treatment effects in clinical trials with the discan metric of the Sheehan Disability Scale. Int Clin Psychopharmacol 2008; 23 (2): 70–83. doi: 10.1097/YIC.0b013e3282f2b4d6.
20. Fagiolini A, Florea I, Loft H et al. Effectiveness of vortioxetine on emotional blunting in patients with major depressive disorder with inadequate response to SSRI/SNRI treatment. J Affect Disord 2021; 283 : 472–479. doi: 10.1016/j.jad.2020.11.106.
21. Kim HK, Blumberger DM, Fitzgerald PB et al. Antidepressant treatment outcomes in patients with and without comorbid physical or psychiatric disorders: a systematic review and meta-analysis. J Affect Disord 2021; 295 : 225–234. doi: 10.1016/j.jad.2021.08.046.
22. Baldwin DS, Necking O, Schmidt SN et al. Efficacy and safety of vortioxetine in treatment of patients with major depressive disorder and common co-morbid physical illness. J Affect Disord 2022; 311 : 588–594. doi: 10.1016/j.jad.2022.05.098.
23. Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry 1979; 134 : 382–389. doi: 10.1192/bjp.134.4.382.
24. Chen G, Højer AM, Areberg J et al. Vortioxetine: clinical pharmacokinetics and drug interactions. Clin Pharmacokinet 2018; 57 (6): 673–686. doi: 10.1007/s40262-017-0612-7.
25. Behlke LM, Lenze EJ, Carney RM. The cardiovascular effects of newer antidepressants in older adults and those with or at high risk for cardiovascular diseases. CNS Drugs 2020; 34 (11): 1133–1147. doi: 10.1007/s40263-020-00763-z.
26. Ozmen O, Tasan S, Unal GO. Vortioxetine’s therapeutic potential: cardiac responses to chronic unpredictable mild stress in a rat model. Arq Bras Cardiol 2025; 122 (2): e20240159. doi: 10.36660/abc.20240159.
27. Kaser M, Zaman R, Sahakian BJ. Cognition as a treatment target in depression. Psychol Med 2017; 47 (6): 987–989. doi: 10.1017/S00 33291716003123.
28. Mørk A, Montezinho LP, Miller S et al. Vortioxetine (Lu AA21004), a novel multimodal antidepressant, enhances memory in rats. Pharmacol Biochem Behav 2013; 105 : 41–50. doi: 10.1016/j.pbb.2013.01.019.
29. Katona C, Hansen T, Olsen CK. A randomized, double-blind, placebo-controlled, duloxetine-referenced, fixed-dose study comparing the efficacy and safety of Lu AA21004 in elderly patients with major depressive disorder. Int Clin Psychopharmacol 2012; 27 (4): 215–223. doi: 10.1097/YIC.0b013e3283542457.
30. Rey A. L’examen clinique en psychologie. 1st ed. Paris: Presses Universitaires de France 1958 : 222.
31. Wechsler D. WAIS-III: Administration and Scoring Manual. San Antonio (TX): Psychological Corporation 1997 : 217.
32. McIntyre RS, Lophaven S, Olsen CK. A randomized, double-blind, placebo-controlled study of vortioxetine on cognitive function in depressed adults. Int J Neuropsychopharmacol 2014; 17 (10): 1557–1567. doi: 10.1017/S1461145714000546.
33. Mahableshwarkar AR, Zajecka J, Jacobson W et al. A randomized, placebo-controlled, active-reference, double-blind, flexible-dose study of the efficacy of vortioxetine on cognitive function in major depressive disorder. Neuropsychopharmacology 2015; 40 (8): 2025–2037. doi: 10.1038/npp.2015.52.
34. Renaud-Charest O, Lui LMW, Eskander S et al. Onset and frequency of depression in post-COVID-19 syndrome: a systematic review. J Psychiatr Res 2021; 144 : 129–137. doi: 10.1016/j.jpsychires.2021.09.054.
35. Di Nicola M, Pepe M, Montanari S et al. Vortioxetine improves physical and cognitive symptoms in patients with post-COVID-19 major depressive episodes. Eur Neuropsychopharmacol 2023; 70 : 21–28. doi: 10.1016/j.euroneuro.2023.02.006.
36. McIntyre RS, Phan L, Kwan ATH et al. Vortioxetine for the treatment of post-COVID-19 condition: a randomized controlled trial. Brain 2024; 147 (3): 849–857. doi: 10.1093/brain/awad377.
37. Talmon M, Rossi S, Pastore A et al. Vortioxetine exerts anti-inflammatory and immunomodulatory effects on human monocytes/macrophages. Br J Pharmacol 2018; 175 (1): 113–124. doi: 10.1111/bph. 14074.
38. Talmon M, Chaudhari RD, Suryavanshi H et al. Design, synthesis and biological evaluation of vortioxetine derivatives as new COX-1/2 inhibitors in human monocytes. Bioorg Med Chem 2020; 28 (23): 115760. doi: 10.1016/j.bmc.2020.115760.
39. Wong AC, Devason AS, Umana IC et al. Serotonin reduction in post-acute sequelae of viral infection. Cell 2023; 186 (22): 4851–4867.e20. doi: 10.1016/j.cell.2023.09.013.
40. Lundberg J, Cars T, Loov SA et al. Clinical and societal burden of incident major depressive disorder: a population-wide cohort study in Stockholm. Acta Psychiatr Scand 2022; 146 (1): 51–63. doi: 10.1111/acps. 13414.
41. Baldwin DS, Florea I, Jacobsen PL et al. A meta-analysis of the efficacy of vortioxetine in patients with major depressive disorder and high levels of anxiety symptoms. J Affect Disord 2016; 206 : 140–150. doi: 10.1016/j.jad.2016.07.015.
42. McIntyre RS, Loft H, Christensen MC. Efficacy of vortioxetine on anhedonia: results from a pooled analysis of short-term studies in patients with major depressive disorder. Neuropsychiatr Dis Treat 2021; 17 : 575–585. doi: 10.2147/NDT.S296451.
43. Chokka P, Hammer-Helmich L, Schmidt SN et al. Functional improvement as a treatment goal in major depressive disorder: a narrative review of the evidence for vortioxetine. Curr Med Res Opin 2025; 41 (5): 855–866. doi: 10.1080/03007995.2025.2503976.
44. McIntyre RS, Necking O, Schmidt SN et al. Minimal clinically important change in the MADRS anhedonia factor score: a pooled analysis of open-label studies with vortioxetine in patients with major depressive disorder. J Affect Disord 2024; 363 : 430–435. doi: 10.1016/j.jad.2024.07.070.
45. Mattingly GW, Ren H, Christensen MC et al. Effectiveness of vortioxetine in patients with major depressive disorder in real-world clinical practice: results of the RELIEVE study. Front Psychiatry 2022; 13 : 824831. doi: 10.3389/fpsyt.2022.824831.
46. Wang G, Gislum M, Filippov G et al. Comparison of vortioxetine versus venlafaxine XR in adults in Asia with major depressive disorder: a randomized, double-blind study. Curr Med Res Opin 2015; 31 (4): 785–794. doi: 10.1185/03007995.2015.1014028.
47. Chokka P, Bougie J, Proulx J et al. Long-term functioning outcomes are predicted by cognitive symptoms in working patients with major depressive disorder treated with vortioxetine: results from the AtWoRC study. CNS Spectr 2019; 24 (6): 616–627. doi: 10.1017/S1092852919000786.
48. Sullivan MJ, Edgley K, Dehoux E. A survey of multiple sclerosis: I. Perceived cognitive problems and compensatory strategy use. Can J Rehabil 1990.
49. Lerner D, Reed JI, Massarotti E et al. The Work Limitations Questionnaire’s validity and reliability among patients with osteoarthritis. J Clin Epidemiol 2002; 55 (2): 197–208. doi: 10.1016/S0895-4356 (01) 00424-3.
50. Üstün TB, Chatterji S, Kostanjsek N et al. Developing the World Health Organization Disability Assessment Schedule 2.0. Bull World Health Organ 2010; 88 (11): 815–823. doi: 10.2471/BLT.09.067231.
Labels
Addictology Paediatric psychiatry PsychiatryArticle was published in
Czech and Slovak Psychiatry
2025 Issue 5
Most read in this issue
- Clozapine-induced myocarditis
- Dual disorder – how (in) consistent terminology affects research, diagnosis, and treatment
- Vortioxetine’s 10 years in Czech psychiatry – history of development and new findings
- Tokophobia: a hidden fear with serious consequences – a challenge for psychiatry and obstetrics