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2016 | 16 | 2 | 99–103

Article title

Wortioksetyna – lek przeciwdepresyjny o wielofunkcyjnym mechanizmie działania

Content

Title variants

EN
Vortioxetine – an antidepressant with a multifunctional mechanism of action

Languages of publication

EN PL

Abstracts

EN
Depression is one of the most invalidating chronic diseases, and the efficacy of the available antidepressants is limited. Remission is observed in only a third of cases of depressive patients following the use of the first drug. Also a third of patients are drug-resistant which means they do not improve despite the administration of multiple drugs. More and more attention is paid to cognitive dysfunctions (such as attention and memory disorders, executive function disorders, slow information processing) which are one of the key symptoms in the course of depression. These are characterised by a high incidence in depressive patients (up to 94% of all patients affected by the episode of depression and up to 44% of patients in remission) and largely affect their quality of life. Vortioxetine is a new antidepressant, with so-called multifunctional mechanism of action, comprising the inhibition of the serotonin transporter, partial agonism of the 5-HT1A and 5-HT1B receptors, and antagonism of the 5-HT3A and 5-HT7 receptors. Vortioxetine has a well-documented anti-depression efficacy both in short- and long-term therapy. Most available data point to the efficacy of the said antidepressant when administered in the daily dose of 10 mg and more, yet the 10 mg dose has a similar efficacy to 15 or 20 mg. Adverse event profile of vortioxetine may be better than for other antidepressants (mainly for duloxetine and venlafaxine). Beneficial effect of vortioxetine on cognitive impairment which may be independent of its antidepressant action is clinically important and interesting. Moreover, in comparison to other antidepressants, vortioxetine has a good tolerability profile in terms of sexual dysfunction and does not significantly affect the body mass and other metabolic parameters.
PL
Depresja pozostaje jedną z najbardziej inwalidyzujących chorób przewlekłych, a skuteczność dostępnych leków przeciwdepresyjnych jest ograniczona. Jedynie około ⅓ pacjentów uzyskuje remisję po zastosowaniu pierwszego leku; również około ⅓ chorych cechuje się lekoopornością, czyli nie uzyskuje poprawy mimo zastosowania różnych leków. Coraz większą uwagę zwraca się na dysfunkcje poznawcze (zaburzenia uwagi, pamięci i funkcji wykonawczych, wolniejsze tempo przetwarzania informacji), należące do kluczowych objawów w przebiegu depresji. Są one częste u pacjentów z depresją (do 94% wszystkich chorych w trakcie epizodu depresji oraz do 44% osób w fazie remisji) i znacząco wpływają na jakość życia. Wortioksetyna jest nowym lekiem przeciwdepresyjnym o wielofunkcyjnym mechanizmie działania, który obejmuje hamowanie transportera serotoniny, częściowy agonizm wobec receptorów 5-HT1A i 5-HT1B oraz antagonizm wobec receptorów 5-HT3A i 5-HT7. Wortioksetyna ma dobrze udokumentowaną skuteczność przeciwdepresyjną – w leczeniu zarówno krótko-, jak i długoterminowym. Najwięcej danych wskazuje na skuteczność leku stosowanego w dawce dobowej 10 mg i wyższej, przy czym dawka 10 mg ma podobną skuteczność jak 15 i 20 mg. Profil działań ubocznych wortioksetyny może być lepszy niż w przypadku innych leków przeciwdepresyjnych (głównie duloksetyny i wenlafaksyny). Uwagę zwraca korzystny wpływ wortioksetyny na zaburzenia poznawcze, który może być niezależny od jej działania przeciwdepresyjnego. Ponadto w porównaniu z innymi lekami przeciwdepresyjnymi wortioksetyna cechuje się dobrym profilem tolerancji w zakresie dysfunkcji seksualnych oraz nie wpływa istotnie na masę ciała i inne parametry metaboliczne.

Discipline

Year

Volume

16

Issue

2

Pages

99–103

Physical description

Contributors

  • Klinika Psychiatrii Wieku Podeszłego i Zaburzeń Psychotycznych, Uniwersytet Medyczny w Łodzi, Łódź, Polska
author
  • Zakład Psychologii Lekarskiej, Uniwersytet Medyczny w Łodzi, Łódź, Polska

References

  • Adell A: Lu-AA21004, a multimodal serotonergic agent, for the potential treatment of depression and anxiety. IDrugs 2010; 13: 900–910.
  • Alvarez E, Perez V, Dragheim M et al.: A double-blind, randomized, placebo-controlled, active reference study of Lu AA21004 in patients with major depressive disorder. Int J Neuropsychopharmacol 2012; 15: 589–600.
  • Areberg J, Søgaard B, Højer AM: The clinical pharmacokinetics of Lu AA21004 and its major metabolite in healthy young volunteers. Basic Clin Pharmacol Toxicol 2012; 111: 198–205.
  • Baldwin DS, Chrones L, Florea I et al.: The safety and tolerability of vortioxetine: analysis of data from randomized placebo-controlled trials and open-label extension studies. J Psychopharmacol 2016; 30: 242–252.
  • Baldwin DS, Loft H, Florea I: Lu AA21004, a multimodal psychotropic agent, in the prevention of relapse in adult patients with generalized anxiety disorder. Int Clin Psychopharmacol 2012; 27: 197–207.
  • Bang-Andersen B, Ruhland T, Jørgensen M et al.: Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder. J Med Chem 2011; 54: 3206–3221.
  • Bonaventure P, Kelly L, Aluisio L et al.: Selective blockade of 5-hydroxytryptamine (5-HT)7 receptors enhances 5-HT transmission, antidepressant-like behavior, and rapid eye movement sleep suppression induced by citalopram in rodents. J Pharmacol Exp Ther 2007; 321: 690–698.
  • Boulenger JP, Loft H, Florea I: A randomized clinical study of Lu AA21004 in the prevention of relapse in patients with major depressive disorder. J Psychopharmacol 2012; 26: 1408–1416.
  • Boulenger JP, Loft H, Olsen CK: Efficacy and safety of vortioxetine (Lu AA21004), 15 and 20 mg/day: a randomized, double-blind, placebo-controlled, duloxetine-referenced study in the acute treatment of adult patients with major depressive disorder. Int Clin Psychopharmacol 2014; 29: 138–149.
  • Celada P, Bortolozzi A, Artigas F: Serotonin 5-HT1A receptors as targets for agents to treat psychiatric disorders: rationale and current status of research. CNS Drugs 2013; 27: 703–716.
  • Citrome L: Vortioxetine for major depressive disorder: an indirect comparison with duloxetine, escitalopram, levomilnacipran, sertraline, venlafaxine, and vilazodone, using number needed to treat, number needed to harm, and likelihood to be helped or harmed. J Affect Disord 2016; 196: 225–233.
  • Conradi HJ, Ormel J, de Jonge P: Presence of individual (residual) symptoms during depressive episodes and periods of remission: a 3-year prospective study. Psychol Med 2011; 41: 1165–1174.
  • Häggström L, Nielsen RZ, Danchenko N et al.: P.2.f.029. A randomised, double-blind, study of vortioxetine versus agomelatine in adults with major depressive disorder (MDD) with inadequate response to SSRI/SNRI treatment. Eur Neuropsychopharmacol 2013; 23 Suppl 2: S412.
  • Henigsberg N, Mahableshwarkar AR, Jacobsen P et al.: A randomized, double-blind, placebo-controlled 8-week trial of the efficacy and tolerability of multiple doses of Lu AA21004 in adults with major depressive disorder. J Clin Psychiatry 2012; 73: 953–959.
  • Hvenegaard MG, Bang-Andersen B, Pedersen H et al.: Identification of the cytochrome P450 and other enzymes involved in the in vitro oxidative metabolism of a novel antidepressant, Lu AA21004. Drug Metab Dispos 2012; 40: 1357–1365.
  • Jacobsen PL, Mahableshwarkar AR, Chen Y et al.: Effect of vortioxetine vs. escitalopram on sexual functioning in adults with welltreated major depressive disorder experiencing SSRI-induced sexual dysfunction. J Sex Med 2015; 12: 2036–2048.
  • Jain R, Mahableshwarkar AR, Jacobsen PL et al.: A randomized, double-blind, placebo-controlled 6-wk trial of the efficacy and tolerability of 5 mg vortioxetine in adults with major depressive disorder. Int J Neuropsychopharmacol 2013; 16: 313–321.
  • Katona C, Hansen T, Olsen CK: A randomized, double-blind, placebocontrolled, 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: 215–223.
  • Kelliny M, Croarkin PE, Moore KM et al.: Profile of vortioxetine in the treatment of major depressive disorder: an overview of the primary and secondary literature. Ther Clin Risk Manag 2015; 11: 1193–1212.
  • Mahableshwarkar AR, Jacobsen PL, Chen Y: A randomized, doubleblind trial of 2.5 mg and 5 mg vortioxetine (Lu AA21004) versus placebo for 8 weeks in adults with major depressive disorder. Curr Med Res Opin 2013; 29: 217–226.
  • 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: 1557–1567.
  • 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.
  • Mørk A, Pehrson A, Brennum LT et al.: Pharmacological effects of Lu AA21004: a novel multimodal compound for the treatment of major depressive disorder. J Pharmacol Exp Ther 2012; 340: 666–675.
  • Pehrson AL, Cremers T, Bétry C et al.: Lu AA21004, a novel multimodal antidepressant, produces regionally selective increases of multiple neurotransmitters – a rat microdialysis and electrophysiology study. Eur Neuropsychopharmacol 2013; 23: 133–145.
  • Rush AJ, Trivedi MH, Wisniewski SR et al.: Acute and longer-term outcomes in depressed outpatients requiring one or several treatmentsteps: a STAR*D report. Am J Psychiatry 2006; 163: 1905–1917.
  • Saltiel PF, Silvershein DI: Major depressive disorder: mechanismbased prescribing for personalized medicine. Neuropsychiatr Dis Treat 2015; 11: 875–888.
  • Sobocki P, Jönsson B, Angst J et al.: Cost of depression in Europe. J Ment Health Policy Econ 2006; 9: 87–98.
  • Stahl SM, Lee-Zimmerman C, Cartwright S et al.: Serotonergic drugs for depression and beyond. Curr Drug Targets 2013; 14: 578–585.
  • Stenkrona P, Halldin C, Lundberg J: 5-HTT and 5-HT1A receptor occupancy of the novel substance vortioxetine (Lu AA21004). A PET study in control subjects. Eur Neuropsychopharmacol 2013; 23: 1190–1198.
  • Theunissen EL, Street D, Højer AM et al.: A randomized trial on the acute and steady-state effects of a new antidepressant, vortioxetine (Lu AA21004), on actual driving and cognition. Clin Pharmacol Ther 2013; 93: 493–501.
  • Uldam HK, Juhl M, Pedersen H et al.: Biosynthesis and identification of an N-oxide/N-glucuronide metabolite and first synthesis of an N-O-glucuronide metabolite of Lu AA21004. Drug Metab Dispos 2011; 39: 2264–2274.

Document Type

review

Publication order reference

Identifiers

YADDA identifier

bwmeta1.element.psjd-d2f7ee08-faa9-420b-9d9e-60730a233202
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