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Review articles
Citrome L. Vortioxetine for major depressive disorder: a systematic review of the efficacy and safety profile for this newly approved antidepressant – what is the number needed to treat, number needed to harm and likelihood to be helped or harmed? Int J Clin Pract. 2014;68:60-82.
Schatzberg AF, Blier P, Culpepper L, Jain R, Papakostas GI, Thase ME. An overview of vortioxetine. J Clin Psychiatry. 2014 Dec;75(12):1411-8. PubMed PMID: 25551236.
Thase ME. US Food and Drug Administration’s review of the novel antidepressant vortioxetine. J Clin Psychiatry. 2015 Jan;76(1):e120-1. PubMed PMID: 25650679.
Zhang J, Mathis MV, Sellers JW, Kordzakhia G, Jackson AJ, Dow A, Yang P, Fossom L, Zhu H, Patel H, Unger EF, Temple RJ. The US Food and Drug Administration’s perspective on the new antidepressant vortioxetine. J Clin Psychiatry. 2015 Jan;76(1):8-14. PubMed PMID: 25562777.
Major Depressive Disorder
Meta-analyses: Major depressive disorder
Thase ME, Mahableshwarkar AR, Dragheim M, Loft H, Vieta E. A meta-analysis of randomized, placebo-controlled trials of vortioxetine for the treatment of major depressive disorder in adults. Eur Neuropsychopharmacol. 2016 Jun;26(6):979-93. PubMed PMID: 27139079.
Short-term, randomized, placebo-controlled trials in major depressive disorder
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(5):589-600.
Baldwin DS, Loft H, Dragheim M. A randomised, double-blind, placebo controlled, duloxetine-referenced, fixed-dose study of three dosages of Lu AA21004 in acute treatment of major depressive disorder (MDD). Eur Neuropsychopharmacol. 2012 Jul;22(7):482-91. doi: 10.1016/j.euroneuro.2011.11.008. Epub 2011 Dec 30. PMID: 22209361.
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 May;29(3):138-49. PubMed PMID: 24257717; PubMed Central PMCID: PMC3979887.
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 Jul;73(7):953-9. doi: 10.4088/JCP.11m07470. PMID: 22901346.
Jacobsen PL, Mahableshwarkar AR, Serenko M, Chan S, Trivedi MH. A randomized, double-blind, placebo-controlled study of the efficacy and safety of vortioxetine 10 mg and 20 mg in adults with major depressive disorder. J Clin Psychiatry. 2015 May;76(5):575-82. PubMed PMID: 26035185.
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 Neuropsychopharmacol. 2013 Mar;16(2):313-21. doi: 10.1017/S1461145712000727. Epub 2012 Sep 11. PMID: 22963932.
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. Curr Med Res Opin. 2013 Mar;29(3):217-26. doi: 10.1185/03007995.2012.761600. Epub 2013 Jan 17. PMID: 23252878.
Mahableshwarkar AR, Jacobsen PL, Serenko M, Chen Y, Trivedi MH. A randomized, double-blind, placebo-controlled study of the efficacy and safety of 2 doses of vortioxetine in adults with major depressive disorder. J Clin Psychiatry. 2015 May;76(5):583-91. PubMed PMID: 26035186.
Mahableshwarkar AR, Jacobsen PL, Chen Y, Serenko M, Trivedi MH. A randomized, double-blind, duloxetine-referenced study comparing efficacy and tolerability of 2 fixed doses of vortioxetine in the acute treatment of adults with MDD. Psychopharmacology (Berl). 2015 Jun;232(12):2061-70. PubMed PMID: 25575488; PubMed Central PMCID: PMC4432084.
Elderly patients
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.
Long-term open-label trial
Baldwin DS, Hansen T, Florea I. Vortioxetine (Lu AA21004) in the long-term open-label treatment of major depressive disorder. Curr Med Res Opin. 2012;28(10):1717-1724. PubMed PMID:22978748
Jacobsen PL, Harper L, Chrones L, Chan S, Mahableshwarkar AR. Safety and tolerability of vortioxetine (15 and 20 mg) in patients with major depressive disorder: results of an open-label, flexible-dose, 52-week extension study.Int Clin Psychopharmacol. 2015 Sep;30(5):255-64. PubMed PMID: 26020712.
Prevention of relapse
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(11):1408-1416.
Inadequate response to SSRI or SNRI
Dragheim M, Nielsen RZ A randomized, double-blind, study of vortioxetine versus agomelatine in adults with major depressive disorder (MDD) switched after inadequate response to SSRI or SNRI treatment. Poster Presentation I-44, 53rd Annual NCDEU Meeting, Hollywood, FL, 28–31 May 2013.
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. 2014 Sep;29(5):470-82. PubMed PMID: 25087600; PubMed Central PMCID: PMC4265248.
Cognitive dysfunction
Al-Sukhni M, Maruschak NA, McIntyre RS. Vortioxetine : a review of efficacy, safety and tolerability with a focus on cognitive symptoms in major depressive disorder. Expert Opin Drug Saf. 2015 Aug;14(8):1291-304. PubMed PMID: 26022537.
Bétry C, Etiévant A, Pehrson A, Sánchez C, Haddjeri N. Effect of the multimodal acting antidepressant vortioxetine on rat hippocampal plasticity and recognition memory. Prog Neuropsychopharmacol Biol Psychiatry. 2015 Apr 3;58:38-46. PubMed PMID: 25524057.
du Jardin KG, Jensen JB, Sanchez C, Pehrson AL. Vortioxetine dose-dependently reverses 5-HT depletion-induced deficits in spatial working and object recognition memory: a potential role for 5-HT1A receptor agonism and 5-HT3 receptor antagonism. Eur Neuropsychopharmacol. 2014 Jan;24(1):160-71. PubMed PMID: 23916504.
Mahableshwarkar AR, Zajecka J, Jacobson W, Chen Y, Keefe RS. 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 Jul;40(8):2025-37. PubMed PMID: 25687662.
McIntyre RS, Harrison J, Loft H, Jacobson W, Olsen CK. The Effects of Vortioxetine on Cognitive Function in Patients with Major Depressive Disorder (MDD): a Meta-Analysis of Three Randomized Controlled Trials. Int J Neuropsychopharmacol. 2016 Jun 15. pii: pyw055. doi: 10.1093/ijnp/pyw055. [Epub ahead of print] PubMed PMID: 27312740.
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 Oct;17(10):1557-67. PubMed PMID: 24787143; PubMed Central PMCID: PMC4162519.
Jensen JB, du Jardin KG, Song D, Budac D, Smagin G, Sanchez C, Pehrson AL. Vortioxetine, but not escitalopram or duloxetine, reverses memory impairment induced by central 5-HT depletion in rats: evidence for direct 5-HT receptor modulation. Eur Neuropsychopharmacol. 2014 Jan;24(1):148-59. PubMed PMID: 24284262.
Kugathasan P, Waller J, Westrich L, Abdourahman A, Tamm JA, Pehrson AL, Dale E, Gulinello M, Sanchez C, Li Y. In vivo and in vitro effects of vortioxetine on molecules associated with neuroplasticity. J Psychopharmacol. 2016 Sep 26. pii: 0269881116667710. [Epub ahead of print] PubMed PMID: 27678087.
Pehrson AL, Hillhouse TM, Haddjeri N, Rovera R, Porter JH, Mørk A, Smagin G, Song D, Budac D, Cajina M, Sanchez C. Task- and Treatment Length-Dependent Effects of Vortioxetine on Scopolamine-Induced Cognitive Dysfunction and Hippocampal Extracellular Acetylcholine in Rats. J Pharmacol Exp Ther. 2016 Sep;358(3):472-82. doi: 10.1124/jpet.116.233924. PubMed PMID: 27402279; PubMed Central PMCID: PMC4998672.
Pehrson AL, Leiser SC, Gulinello M, Dale E, Li Y, Waller JA, Sanchez C. Treatment of cognitive dysfunction in major depressive disorder–a review of the preclinical evidence for efficacy of selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors and the multimodal-acting antidepressant vortioxetine. Eur J Pharmacol. 2015 Apr 15;753:19-31. PubMed PMID: 25107284.
Smagin GN, Song D, Budac DP, Waller JA, Li Y, Pehrson AL, Sánchez C. Histamine may contribute to vortioxetine’s procognitive effects; possibly through an orexigenic mechanism. Prog Neuropsychopharmacol Biol Psychiatry. 2016 Jul 4;68:25-30. PubMed PMID: 26945513.
Wallace A, Pehrson AL, Sánchez C, Morilak DA. Vortioxetine restores reversal learning impaired by 5-HT depletion or chronic intermittent cold stress in rats. Int J Neuropsychopharmacol. 2014 Oct;17(10):1695-706. PubMed PMID: 24852131; PubMed Central PMCID: PMC4162520.
Westrich L, Haddjeri N, Dkhissi-Benyahya O, Sánchez C. Involvement of 5-HT₇ receptors in vortioxetine’s modulation of circadian rhythms and episodic memory in rodents. Neuropharmacology. 2015 Feb;89:382-90. PubMed PMID: 25446573.
Sexual dysfunction
Jacobsen PL, Mahableshwarkar AR, Chen Y, Chrones L, Clayton AH. Effect of Vortioxetine vs. Escitalopram on Sexual Functioning in Adults with Well-Treated Major Depressive Disorder Experiencing SSRI-Induced Sexual Dysfunction. J Sex Med. 2015 Oct;12(10):2036-48. PubMed PMID: 26331383.
Jacobsen PL, Mahableshwarkar AR, Palo WA, Chen Y, Dragheim M, Clayton AH. Treatment-emergent sexual dysfunction in randomized trials of vortioxetine for major depressive disorder or generalized anxiety disorder: a pooled analysis. CNS Spectr. 2016 Oct;21(5):367-378. PubMed PMID: 26575433.
Segraves RT. Editorial Comment on “The Effect of Vortioxetine vs. Escitalopram on Sexual Functioning in Adults with Well-Treated Major Depressive Disorder Experiencing SSRI-Induced Sexual Dysfunction”. J Sex Med. 2015 Oct;12(10):2049-50. PubMed PMID: 26440559.
Generalized Anxiety Disorder
Meta-analysis: GAD
Fu J, Peng L, Li X. The efficacy and safety of multiple doses of vortioxetine for generalized anxiety disorder: a meta-analysis. Neuropsychiatr Dis Treat. 2016 Apr 19;12:951-9. PubMed PMID: 27143896; PubMed Central PMCID: PMC4844447.
Pae CU, Wang SM, Han C, Lee SJ, Patkar AA, Masand PS, Serretti A. Vortioxetine, a multimodal antidepressant for generalized anxiety disorder: a systematic review and meta-analysis. J Psychiatr Res. 2015 May;64:88-98. PubMed PMID: 25851751.
Short-term, placebo-controlled clinical trials in GAD
Bidzan L, Mahableshwarkar AR, Jacobsen P, Yan M, Sheehan DV. Vortioxetine (Lu AA21004) in generalized anxiety disorder: results of an 8-week, multinational, randomized, double-blind, placebo-controlled clinical trial. Eur Neuropsychopharmacol. 2012 Dec;22(12):847-57. PubMed PMID: 22898365.
Mahableshwarkar AR, Jacobsen PL, Chen Y, Simon JS. A randomised, double-blind, placebo-controlled, duloxetine-referenced study of the efficacy and tolerability of vortioxetine in the acute treatment of adults with generalised anxiety disorder. Int J Clin Pract. 2014 Jan;68(1):49-59. PubMed PMID: 24341301.
Mahableshwarkar AR, Jacobsen PL, Serenko M, Chen Y. A randomized, double-blind, fixed-dose study comparing the efficacy and tolerability of vortioxetine 2.5 and 10 mg in acute treatment of adults with generalized anxiety disorder. Hum Psychopharmacol. 2014 Jan;29(1):64-72. PubMed PMID: 24424707.
Rothschild AJ, Mahableshwarkar AR, Jacobsen P, Yan M, Sheehan DV. Vortioxetine (Lu AA21004) 5 mg in generalized anxiety disorder: results of an 8-week randomized, double-blind, placebo-controlled clinical trial in the United States. Eur Neuropsychopharmacol. 2012 Dec;22(12):858-66. PubMed PMID: 22901736.
Relapse prevention clinical trials in GAD
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 Jul;27(4):197-207. PubMed PMID: 22475889.
Pharmacology
Stahl SM. Modes and nodes explain the mechanism of action of vortioxetine, a multimodal agent (MMA): enhancing serotonin release by combining serotonin (5HT) transporter inhibition with actions at 5HT receptors (5HT1A, 5HT1B, 5HT1D, 5HT7 receptors). CNS Spectr. 2015 Apr;20(2):93-7. PubMed PMID: 25831967.
Stahl SM. Modes and nodes explain the mechanism of action of vortioxetine, a multimodal agent (MMA): actions at serotonin receptors may enhance downstream release of four pro-cognitive neurotransmitters. CNS Spectr. 2015 Jun 11:1-5. PubMed PMID: 26062986.
Stahl SM. Modes and nodes explain the mechanism of action of vortioxetine, a multimodal agent (MMA): modifying serotonin’s downstream effects on glutamate and GABA (gamma amino butyric acid) release. CNS Spectr. 2015 Jun 11:1-6. PubMed PMID: 26062900.
Chen G, Zhang W, Serenko M. Lack of effect of multiple doses of vortioxetine on the pharmacokinetics and pharmacodynamics of aspirin and warfarin. J Clin Pharmacol. 2015 Jun;55(6):671-9. PubMed PMID: 25641606.
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