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06.10.2015 | Fortbildung

Multimodale Wirkstoffe

Antidepressivum mit unterschiedlichen Zielstrukturen und Wirkmechanismen

verfasst von: Prof. Dr. med. Hans-Peter Volz

Erschienen in: DNP – Die Neurologie & Psychiatrie | Ausgabe 10/2015

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Zusammenfassung

Vortioxetin ist ein neues Antidepressivum, das im Mai dieses Jahres auch in Deutschland eingeführt wurde. Derzeit steht die Bewertung eines Zusatznutzens durch den Gemeinsamen Bundesausschuss (G-BA) an. Die vorliegende Darstellung, angelehnt an eine kurze Monografie des Autors [1], fasst die Datenlage zu dieser Substanz zusammen.

Volz HP. Blickpunkt Vortioxetin. Linkenheim-Hochstetten: Aesopus Verlag, 2014.

Nutt DJ. Beyond psychoanaleptics - can we improve antidepressant drug nomenclature? J Psychopharmacol 2009; 23: 343–345CrossRefPubMed

Pehrson AL, Cremers T, Bétry C, van der Hart MG, Jørgensen L, Madsen M, Haddjeri N, Ebert B, Sanchez C. Lu AA21004, a novel multimodal antidepressant, produces regionally selective increases of multiple neurotransmitters - a rat microdialysis and electrophysiology study. Eur Neuropsychpharmacol 2013; 23: 133–145CrossRef

Bosker FJ, van Esseveldt KE, Klompmakers AA, Westenberg HG. Chronic treatment with fluvoxamine by osmotic minipumps fails to induce persistent functional changes in central 5-HT1A and 5-HT1B receptors, as measured by in vivo microdialysis in dorsal hippocampus of conscious rats. Psychopharmacology (Berl) 1995; 117: 358–363CrossRef

Cremers TI, de Boer P, Liao Y, Bosker FJ, den Boer JA, Westerink BH, Wikström HV. Augmentation with a 5-HT(1A), but not a 5-HT(1B) receptor antagonist critically depends on the dose of citalopram. Eur J Pharmacol 2000; 397: 63–74CrossRefPubMed

Malagié I, Trillat AC, Bourin M, Jacquot C, Hen R, Gardier AM. 5-HT1B Autoreceptors limit the effects of selective serotonin re-uptake inhibitors in mouse hippocampus and frontal cortex. J Neurochem 2001; 76: 865–871CrossRefPubMed

De Groote L, Klompmakers AA, Olivier B, Westenberg HG. Role of extracellular serotonin levels in the effect of 5-HT1B receptor blockade. Psychpharmacology (Berl). 2003; 167: 153–158

Adell A, Celada P, Artigas F. The role of 5-HT1B receptors in the regulation of serotonin cell firing and release in the rat brain. J Neurochem 2001; 79: 172–182CrossRefPubMed

Bang-Andersen B, Ruhland T, Jørgensen M, Smith G, Frederiksen K, Jensen KG, Zhong H, Nielsen SM, Hogg Mørk A, Stebnsbøl TB. 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: 3206–3221CrossRefPubMed

10.

Mørk A, Pehrson A, Brennum LT, Nielsen SM, Zhong H, Lassen AB, Miller S, Westrich L, Boyle NJ, Sánchez C, Fischer CW, Liebenberg N, Wegener G, Bundgaard C, Hogg S, Bang-Andersen B, Stensbøl TB. Pharmacological effects of Lu AA21004: a novel multimodal compound for the treatment of major depressive disorder. J Pharmacol Exp Ther 2012; 340: 666–675CrossRefPubMed

11.

Bétry C, Pehrson AL, Etiévant A, Ebert B, Sánchez C, Haddjeri N. The rapid recovery of 5-HT cell firing induced by the antidepressant vortioxetine involves 5-HT(3) receptor antagonism. Int J Neuropsychopharmacol 2013; 16: 1115–1127CrossRefPubMed

12.

Mørk A, Pehrson A, Fallon SM, Sánchez C, Overstreet DH. Augmentation of SSRI-induced antidepressant-like effect and SSRI-induced increase in serotonin levels by co-administration of a 5-HT3 receptor antagonist [poster]. 66th Annual Meeting of the Society of Biological Psychiatry, May 12-14, San Francisco, CA, USA, 2011.

13.

Giovannini MG, Ceccarelli I, Molinari B, Cecchi M, Goldfarb J, Blandina P. Serotonergic modulation of acetylcholine release from cortex of freely moving rats. J Pharmacol Exp Ther 1998; 285: 1219–122PubMed

14.

Matsumoto M, Yoshioka M, Togashi H, Tochihara M, Ikeda T, Saito H. Modulation of norepinephrine release by serotonergic receptors in the rat hippocampus as measured by in vivo microdialysis. J Pharmacol Exp Ther. 1995; 272: 1044–1051PubMed

15.

Morales M, Battenberg E, de Lecea L, Bloom FE. The type 3 serotonin receptor is expressed in a subpopulation of GABAergic neurons in the rat neocortex and hippocampus. Brain Res 1996; 731: 199–202CrossRefPubMed

16.

Yan Z. Regulation of GABAergic inhibition by serotonin signaling in prefrontal cortex: molecular mechanisms and functional implications. Mol Neurobiol 2002; 26: 203–216CrossRefPubMed

17.

Ballaz SJ, Akil H, Wastson SJ. The 5-HT7 receptor: role in novel object discrimination and relation to novelty-seeking behavior. Neuroscience 2007; 149: 192–202.CrossRefPubMed

18.

Sánchez C, Nielsen SM, Pehrson A, Zhong H, Lassen AB, Bisulo S, Moore N, Mørk A, Wegener G, Stensbol DB. The novel antidepressant LU AA21004 exerts its multimodal activitiy throuh serotonergic targets. Presented at the 24th Congress of the European College of Neuropsychopharmacology, 3-7 September 2011, Paris, France

19.

Pehrson A, Cremers T, Westerink B, Jørgensen L, Madsen M, Ebert B, Sánchez C. Acute and subchronic LU AA 21004 induces monoamine release through a mechanism involving multiple serotonergic receptors. Presented at the 24th Congress of the European College of Neuropsychopharmacology, 3-7 September 2011, Paris, France

20.

Haddjeri N, Etiévant A, Pehrson A, Sánchez A, Bétry C. Effects of the multimodal antidepressant vortioxetine (LU AA21004) on rat synaptic and cellular hippocampal plasticity and memory recognition. Presented at the 25th Congress of the European College of Neuropsychopharmacology, 13-17 October 2012, Wien, Austria

21.

Theunissen EL, Street D, Højer AM, Vermeeren A, van Oers A, Ramaekers JG. 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: 493–501CrossRefPubMed

22.

Nilausen D, Hojer AM, Bendahl L. Absorption, metabolism and excretion of an oral dose of [14C]-LU AA21004 50 mg in healthy men (abstract). J Clin Pharmacol 2009; 49: 1113

23.

Wang Y, Munsaka M, Hanson E, et al. The effect of multiple-doses of fluconazole, or ketoconazole, on the single-dose pharmacokinetic profile in healthy adult subjects (abstract). AAPS 2010a; J12 (S2): T2381

24.

Hvenegaard MG, Bang-Andersen B, Pedersen H, Jørgensen M, Püschl A, Dalgaard L. Identification of the cytochrome P450 and other enzymes involved in the in vitro oxidative metabolism of a novel antidepressant, LU AA 21004. Drugs Met Dis 2012; 40: 1357–1365CrossRef

25.

Buchbjerg JK, Hojer AM, Jensen KG, Sogaard B. Assessment oft he CYP2C19 interaction potential of LU AA21004. J Clin Pharmacol 2009; 49: 1119

26.

Wang Y, Wojtkowski T, Hanson E, et al. An open-label, multiple-dose study in healthy adults to assess the drug interaction potential of Lu AA21004 using the Indiana cocktail (abstract). J Clin Pharmacol 2009a; 49: 1114

27.

Areberg J, Luntang-Jensen M, Søgaard B, Nilausen DØ. Occupancy of the serotonin transporter after administration of Lu AA21004 and its relation to plasma concentration in healthy subjects. Basic Clin Pharmacol Toxicol 2011; 110: 401–404CrossRefPubMed

28.

Chen G, Lee R, Højer AM, Buchbjerg JK, Serenko M, Zhao Z. Pharmacokinetic drug interactions involving vortioxetine (Lu AA21004), a multimodal antidepressant. Clin Drug Investig 2013; 33: 727–736PubMedCentralCrossRefPubMed

29.

Wang Y, Wojtkoski T, Agyemang A, Homery MC, Karim A. Effect of food on the pharmacokinetics of Lu AA21004 in healthy volunteers (abstract). J Clin Pharmacol 2009b; 49: 1115

30.

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: 198–205PubMed

31.

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: 1190–1198CrossRefPubMed

32.

Wang Y, Nomikos GG, Karim A, Munsaka M, Serenko M, Liosatos M, Harris S. Effect of Vortioxetine on Cardiac Repolarization in Healthy Adult Male Subjects: Results of a Thorough QT/QTc Study. Clin Pharmacol Drug Developm 2013; 2: 298–309CrossRef

33.

Alvarez E, Perez V, Dragheim M, Loft H, Artigas F. A double-blind, randomized, placebo-controlled, active reference study of Lu AA21004 in patients with major depressive disorder. Int J Neuropsychopharmacol 2012; 15: 589–600PubMedCentralCrossRefPubMed

34.

Baldwin DS, Loft H, Dragheim M. A randomized, double-blind, placebo controlled, duloxetine-referenced, fixed-dose study of three dosages of LU AA21004 in acute treatment of major depressive disorder. Europ Neuropsychopharmacol 2012a; 22: 482–491CrossRef

35.

Henigsberg N, Mahableshwarkar AR, Jacobsen P, Chen Y, Thase ME. 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: 953–959CrossRefPubMed

36.

Jain R, Mahableshwarkar AR, Jacobsen PL, Chen Y, Thase ME. 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 Neuropsychopharmacology 2013, 16: 313–332CrossRef

37.

Mahableshwarkar AR, Jacobsen PL, Chen Y. A randomized, double-blind trial of 2.5 mg and 5 mg vortioxetine (LU AA21004) versus placebo for 8 weeks in adults with major depressive disorder. CMRO 2013; 29: 217–226

38.

Montgomery SA, Nielsen RZ, Poulsen LH, Häggström L. 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 Clin Exp 2014; 29: 470–482CrossRef

39.

Otte C. Vortioxetin und kognitive Dysfunktion bei der Major Depression. PTT 2015, 22: 25–34

40.

Katona C, Hansen T, Olsen CK. A randomized, double-blind, placebo-controlled, duloxetine-referenced, fixed-dose study comparing the efficacy and safety of LU AA 21004 in elderly patients with major depressive disorder. Int Clin Psychopharmacol 2012; 27: 215–223CrossRefPubMed

41.

Raskin J, Wiltse CG, Siegal A, Sheikh J, Xu J, Dinkel JJ, Rotz BT, Mohs RC. Efficacy of duloxetine on cognition, depression, and pain in elderly patients with major depressive disorder: an 8-week, double-blind, placebo-conrktrolled trial. Am J Psychiatry 2007; 164: 900–909CrossRefPubMed

42.

McIntyre RS, Lophaven S, Olsen CK. A study of vortioxetine on cognitive function in depressed adults. Int J Neuropsychopharmacology 2014; ??: 1–11

43.

Mahableshwarkar AR, Zajecka J, Jacobson W, Chen Y, Keefe RSE. Efficacy of Vortioxetine on Cognitive Function in Adult Patients with Major Depressive Disorder: Results of a Randomized, Double-Blind, Active-Referenced, Placebo-Controlled Trial. Poster presented at the 29th CINP World Congress of Neuropsychopharmacology, 22-26 June 2014, Vancouver, Canada.

44.

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: 1408–1416CrossRefPubMed

45.

Baldwin DS, Hansen T, Florea I. Vortioxetine (LU AA21004) in the long-term open-label treatment of major depressive disorder. CMRO 2012b; 28: 1717–1724

46.

Baldwin DS, Serenko M, Palo P, Lophaven S, Matz J. The safety and tolerability of vortioxetine (Lu AA21004) in the treatment of adults with major depressive disorder. Poster presented at the 13th International Forum and Mood and Anxiety Disorders (IDMAD), Monaco, 2013

47.

Wang Y, Wojtkowski T, Ross G, et al. Effect of multiple doses of rifampicin on the single dose pharmacokinetics of Lu 1121004 (abstract). J Clin Pharmacol 2010 b; 50: 1082CrossRef

Titel: Multimodale Wirkstoffe
Antidepressivum mit unterschiedlichen Zielstrukturen und Wirkmechanismen
verfasst von: Prof. Dr. med. Hans-Peter Volz
Publikationsdatum: 06.10.2015
Verlag: Urban & Vogel
Erschienen in: DNP – Die Neurologie & Psychiatrie / Ausgabe 10/2015
Print ISSN: 2731-8168
Elektronische ISSN: 2731-8176
DOI: https://doi.org/10.1007/s15202-015-0928-9

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