Vortioxetine is the new antidepressant on the block which has been described to have a novel mechanism of action–it directly works on multiple receptors of the neurotransmitter serotonin and it also inhibits serotonin reuptake. It has been shown to have promising antidepressant, antianxiety and pro-cognitive action especially during treatment of major depression. This article gives a brief overview of vortioxetine–its clinical use, pharmacological profile, and safety and tolerability. Most of the studies till date have found vortioxetine to be clinically efficacious, and it also improved the cognitive profile in patients with depression. It has a favorable adverse effect profile- it has been shown to be tolerated well by most subjects in clinical trials where nausea was the most frequently reported side effect, and it also showed the added advantage of comparatively less incidence of unwarranted sexual adverse effects.
World Health Organization and Department of Mental Health and Substance Abuse. Victorian Health Promotion Foundation. University of Melbourne. Promoting mental health: concepts, emerging evidence, practice: summary report. Geneva, Switzerland: World Health Organization; 2004. Available from: http://www.who.int/mental_health/evidence/en/ promoting_mhh.pdf. Accessed July 22, 2015.
US Food and Drug Administration. FDA approves new drug to treat major depressivedisorder. Press release. September 30, 2013. Updated October 10, 2013. www.fda.gov/NewsEvents/ Newsroom/PressAnnouncements/ucm370416.htm. Accessed October 23, 2013.
Stahl SM. Stahl's Essential Psychopharmacology:Neuroscien tific Basis and Practical Application. 4th ed. New York, New York: Cambridge University Press; 2013.
Celada P, Bortolozzi A, Artigas F. Serotonin 5-HT 1A receptors as targets for agents to treat psychiatric disorders: rationale and current status of research. CNS drugs. 2013 Sep 1;27(9):703-716.
Owens MJ, Nemeroff CB. Role of serotonin in the pathophysiology of depression: focus on the serotonin transporter. Clinical chemistry. 1994 Feb 1;40(2):288-295.
Bang-Andersen B, Ruhland T, Jørgensen M, Smith G, Frederiksen K, Jensen KG, Zhong H, Nielsen SM, Hogg S, Mørk A, Stensbøl TB. Discovery of 1-[2-(2, 4-dimethylphenylsulfanyl) phenyl] piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder. Journal of medicinal chemistry. 2011 Apr 12;54(9):3206-3221.
Hvenegaard MG, Bang-Andersen B, Pedersen H, Jorgensen M, Puschl A, Dalgaard L. Identification of the cytochrome P450 and other enzymes involved in the in vitro oxidative metabolism of a novel antidepressant, Lu AA21004. Drug Metabolism and Disposition. 2012 Jan 1:40(7):1357-1365.
Chen G, Lee R, Højer AM, Buchbjerg JK, Serenko M, Zhao Z. Pharmacokinetic drug interactions involving vortioxetine (Lu AA21004), a multimodal antidepressant. Clinical drug investigation. 2013 Oct 1;33(10):727-736.
Baldwin DS, Loft H, Dragheim M. A randomised, doubleblind, placebo controlled, duloxetine-referenced, fixed-dose study of three dosages of Lu AA21004 in acute treatment of major depressive disorder (MDD). European Neuropsychopharmacology. 2012 Jul 1;22(7):482-491.
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. International clinical psychopharmacology. 2012 Jul 1;27(4):215-223.
McIntyre RS, Lophaven S, Olsen CK. A randomized, doubleblind, placebo-controlled study of vortioxetine on cognitive function in depressed adults. International Journal of Neuropsychopharmacology. 2014 Oct 1;17(10):1557-1567.
Häggström L, Nielsen RZ, Poulsen L, Danchenko N. A randomised, double blind, active controlled study of vortioxetine (10-20 mg/day) versus agomelatine 25-50 mg/day) in adults with Major Depressive Disorder with inadequate response to antidepressant treatment. In Poster presented at: 26th Congress of the European College of Neuropsychopharmacology (ECNP) 2013 Oct 5 (pp. 5-9).
Alvarez E, Perez V, Dragheim M, Loft H, Artigas F. A doubleblind, randomized, placebo-controlled, active reference study of Lu AA21004 in patients with major depressive disorder. International Journal of Neuropsychopharmacology. 2012 Jun 1;15(5):589-600.
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. International clinical psychopharmacology. 2014 May;29(3):138-149.
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. The Journal of clinical psychiatry. 2012 Jul;73(7):953-959.
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. The Journal of clinical psychiatry. 2015 May 27;76(5):575-582.
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. International Journal of Neuropsychopharmacology. 2012 Sep 11;16(2):313-321.
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. 2015 Jun 1;232(12):2061-2070.
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. Current medical research and opinion. 2013 Mar 1;29(3):217-226.
Mahableshwarkar AR, Jacobsen PL, Serenko M, Chen Y, Trivedi MH. A duloxetine-referenced, fixed dose study comparing efficacy and safety of 2 vortioxetine doses in the acute treatment of adult MDD patients. In American Psychiatric Association (APA) 166th Annual Meeting 2013 May 8.
Alvarez E, Perez V, Artigas F. Pharmacology and clinical potential of vortioxetine in the treatment of major depressive disorder. Neuropsychiatric disease and treatment. 2014;10:1297-1307.
Boulenger JP, Loft H, Florea I. A randomized clinical study of Lu AA21004 in the prevention of relapse in patients with major depressive disorder. Journal of Psychopharmacology. 2012 Nov;26(11):1408-1416.
Baldwin DS, Hansen T, Florea I. Vortioxetine (Lu AA21004) in the long-term open-label treatment of major depressive disorder. Current medical research and opinion. 2012 Oct 1;28(10):1717-1724.
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. Clinical Pharmacology & Therapeutics. 2013 Jun;93(6):493-501.
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.
Baldwin DS, Serenko M, Palo W, Lophaven S, Matz J. The safety and tolerability of vortioxetine (Lu AA21004) in the treatment of adults with major depressive disorder (MDD): a pooled analysis. International Journal of Psychiatry in Clinical Practice. 2013;17:16-17.
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?. International journal of clinical practice. 2014 Jan;68(1):60-82.
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. The journal of sexual medicine. 2015 Oct;12(10):2036-2048.