Vortioxetine: Difference between revisions

{{Use dmy dates|date=DecemberJune 20222024}}

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| pronounce = {{IPAc-en|v|ɔːr|t|i|ˈ|ɒ|k|s|ə|t|iː|n}} {{respell|vor|tee|OK|sə|teen}}

| ATC_supplemental =

| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 March 2023 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=3 August 2023-08-03 |access-date=2023-08-16 August 2023 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=4 April 2023-04-04}}</ref>

| legal_UK_comment = <ref>{{cite web | title=Brintellix tablets 5, 10 and 20mg - Summary of Product Characteristics (SmPC) | website=(emc) | date=11 April 2022 | url=https://www.medicines.org.uk/emc/product/10443/smpc | access-date=19 December 2022 | archive-date=19 December 2022 | archive-url=https://web.archive.org/web/20221219082241/https://www.medicines.org.uk/emc/product/10443/smpc | url-status=dead }}</ref>

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| bioavailability = 75% (peak at 7–11 hours)<ref name="pmid29189941" />

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| index2_label = as salt

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| IUPAC_name = 1-[2-(2,4-Dimethyl-phenylsulfanyl)phenyl]piperazine

'''Vortioxetine''', sold under the brand namesname '''Trintellix''' and '''Brintellix''' among others, is an [[antidepressant]] of the [[serotonin modulator and stimulator]] (SMS) class.<ref name=AHFS2019/><ref name=webmmd>{{cite web|url=https://www.webmd.com/drugs/2/drug-165165/vortioxetine-oral/details|title=Vortioxetine Tablet - Uses, Side Effects, and More|website=WebMD|access-date=13 April 2024}}</ref> Its effectiveness is viewed as similar to that of other [[antidepressants]].<ref name=AHFS2019/> It is taken [[Oral administration|orally]].<ref name=AHFS2019>{{cite web |title=Vortioxetine Hydrobromide Monograph for Professionals |url=https://www.drugs.com/monograph/vortioxetine-hydrobromide.html |website=Drugs.com |publisher=American Society of Health-System Pharmacists |access-date=18 March 2019 }}</ref>

Common [[side effect]]s include [[nausea]], [[vomiting]], [[constipation]], and [[sexual dysfunction]].<ref name=AHFS2019/><ref name="Trintellix FDA label" /> Serious side effects may include [[suicide]] in those under the age of 25, [[serotonin syndrome]], [[bleeding]], [[mania]], and [[SIADH]].<ref name=AHFS2019/> A [[antidepressant discontinuation syndrome|withdrawal syndrome]] may occur if the medication is abruptly stopped or the dose is decreased.<ref name=AHFS2019/> Use during [[pregnancy]] and [[breastfeeding]] is not generally recommended.<ref name=BNF76>{{cite book|title=British national formulary : BNF 76|date=2018|publisher=Pharmaceutical Press|isbn=9780857113382|pages=376|edition=76}}</ref> Vortioxetine's [[mechanism of action]] is not entirely understood, but is believed to be related to increasing [[serotonin]] levels and possibly interacting with certain serotonin [[receptor (biochemistry)|receptors]] for serotonin.<ref name=AHFS2019/><ref name="pmid25907797" /><ref name="pmid25562777" />

Vortioxetine is usedutilized as a treatment for [[major depressive disorder]].,<ref name=AHFS2019/> Effectivenesswith its effectiveness appearsshown to be similar to other [[antidepressants]]<ref name=AHFS2019/><ref name="Long 2019 pp. 819–820">{{cite journal | vauthors = Long JD | title = Vortioxetine for Depression in Adults | journal = Issues in Mental Health Nursing | volume = 40 | issue = 9 | pages = 819–820 | date = September 2019 | pmid = 31225773 | doi = 10.1080/01612840.2019.1604920 | publisher = Informa UK Limited | s2cid = 195192772 }}</ref><ref name="pmid29477251">{{cite journal | vauthors = Cipriani A, Furukawa TA, Salanti G, Chaimani A, Atkinson LZ, Ogawa Y, Leucht S, Ruhe HG, Turner EH, Higgins JP, Egger M, Takeshima N, Hayasaka Y, Imai H, Shinohara K, Tajika A, Ioannidis JP, Geddes JR | title = Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis | journal = Lancet | volume = 391 | issue = 10128 | pages = 1357–1366 | date = April 2018 | pmid = 29477251 | pmc = 5889788 | doi = 10.1016/S0140-6736(17)32802-7 | url = }}</ref> and its [[effect size]] has been described as modest.<ref name="pmid28499187">{{cite journal | vauthors = Sowa-Kućma M, Pańczyszyn-Trzewik P, Misztak P, Jaeschke RR, Sendek K, Styczeń K, Datka W, Koperny M | title = Vortioxetine: A review of the pharmacology and clinical profile of the novel antidepressant | journal = Pharmacol Rep | volume = 69 | issue = 4 | pages = 595–601 | date = August 2017 | pmid = 28499187 | doi = 10.1016/j.pharep.2017.01.030 | s2cid = 43104089 | url = }}</ref> Vortioxetine may be used when other treatments have failed.<ref name="Trintellix FDA label" /><ref>{{cite journal | vauthors = Connolly KR, Thase ME | title = Vortioxetine: a New Treatment for Major Depressive Disorder | journal = Expert Opinion on Pharmacotherapy | volume = 17 | issue = 3 | pages = 421–31 | date = 2016 | pmid = 26679430 | doi = 10.1517/14656566.2016.1133588 | quote = The authors suggest that vortioxetine is currently a good second-line antidepressant option and shows promise, pending additional long-term data, to become a first-line antidepressant option. | s2cid = 40432194 }}</ref><ref>{{cite journal | vauthors = Köhler S, Cierpinsky K, Kronenberg G, Adli M | title = The serotonergic system in the neurobiology of depression: Relevance for novel antidepressants | journal = Journal of Psychopharmacology | volume = 30 | issue = 1 | pages = 13–22 | date = January 2016 | pmid = 26464458 | doi = 10.1177/0269881115609072 | s2cid = 21501578 }}</ref><ref name=KellinyRev2015>{{cite journal | vauthors = Kelliny M, Croarkin PE, Moore KM, Bobo WV | title = Profile of vortioxetine in the treatment of major depressive disorder: an overview of the primary and secondary literature | journal = Therapeutics and Clinical Risk Management | volume = 11 | pages = 1193–212 | year = 2015 | pmid = 26316764 | pmc = 4542474 | doi = 10.2147/TCRM.S55313 | doi-access = free | title-link = doi }}</ref> A 2017 [[Cochrane (organisation)|Cochrane]] review on vortioxetine determined that theits place for it in the treatment of severe depression is unclear due to low-quality evidence and that more studies comparing vortioxetine to [[selective serotonin reuptake inhibitor]]s (SSRIs), the typical first-line treatments, are needed.<ref>{{cite journal | vauthors = Koesters M, Ostuzzi G, Guaiana G, Breilmann J, Barbui C | title = Vortioxetine for depression in adults | journal = The Cochrane Database of Systematic Reviews | volume = 2017 | pages = CD011520 | date = July 2017 | issue = 7 | pmid = 28677828 | pmc = 6483322 | doi = 10.1002/14651858.CD011520.pub2 }}</ref> Vortioxetine appears to work in depressed patients with anxiety.<ref>{{cite journal | vauthors = Mattingly GW, Ren H, Christensen MC, Katzman MA, Polosan M, Simonsen K, Hammer-Helmich L | title = Effectiveness of Vortioxetine in Patients With Major Depressive Disorder in Real-World Clinical Practice: Results of the RELIEVE Study | journal = Frontiers in Psychiatry | volume = 13 | pages = 824831 | date = 2022 | pmid = 35356713 | doi = 10.3389/fpsyt.2022.824831 | pmc = 8959350 | doi-access = free }}</ref>

Vortioxetine is also used [[off-label use|off-label]] for [[anxiety]].<ref>{{cite journal | vauthors = Pae CU, Wang SM, Han C, Lee SJ, Patkar AA, Masand PS, Serretti A | title = Vortioxetine, a multimodal antidepressant for generalized anxiety disorder: a systematic review and meta-analysis | journal = Journal of Psychiatric Research | volume = 64 | pages = 88–98 | date = May 2015 | pmid = 25851751 | doi = 10.1016/j.jpsychires.2015.02.017 }}</ref> A 2016 review found it was not useful in [[generalized anxiety disorder]] at 2.5, 5, and 10 mg doses (15 and 20 mg doses were not tested).<ref>{{cite journal | vauthors = Fu J, Peng L, Li X | title = The efficacy and safety of multiple doses of vortioxetine for generalized anxiety disorder: a meta-analysis | journal = Neuropsychiatric Disease and Treatment | volume = 12 | pages = 951–9 | date = 19 April 2016 | pmid = 27143896 | pmc = 4844447 | doi = 10.2147/NDT.S104050 | doi-access = free }}</ref> A 2019 [[meta-analysis]] found that vortioxetine did not produce statistically significant results over placebo in the symptoms, quality of life, and remission rates of generalized anxiety disorder, but it was well-tolerated.<ref>{{cite journal | vauthors = Qin B, Huang G, Yang Q, Zhao M, Chen H, Gao W, Yang M | title = Vortioxetine treatment for generalised anxiety disorder: a meta-analysis of anxiety, quality of life and safety outcomes | journal = BMJ Open | volume = 9 | issue = 11 | pages = e033161 | date = November 2019 | pmid = 31784448 | pmc = 6924794 | doi = 10.1136/bmjopen-2019-033161 }}</ref> However, a 2018 meta-analysis supported use and efficacy of vortioxetine for generalized anxiety disorder, though stated that more research was necessary to strengthen the evidence.<ref name="pmid29149828">{{cite journal | vauthors = Yee A, Ng CG, Seng LH | title = Vortioxetine Treatment for Anxiety Disorder: A Meta-Analysis Study | journal = Current Drug Targets | volume = 19 | issue = 12 | pages = 1412–1423 | date = 2018 | pmid = 29149828 | doi = 10.2174/1389450118666171117131151 | s2cid = 11855728 }}</ref> A 2021 [[systematic review]] and meta-analysis concluded that there was uncertainty about the effectiveness of vortioxetine for anxiety due to existing evidence being of very low-quality.<ref name="pmid34038400">{{cite journal | vauthors = Meza N, Leyton F | title = Vortioxetine for generalised anxiety disorder in adults | language = es | journal = Medwave | volume = 21 | issue = 3 | pages = e8172 | date = April 2021 | pmid = 34038400 | doi = 10.5867/medwave.2021.03.8171 | doi-access = free | title-link = doi }}</ref> In a 2020 [[network meta-analysis]] of [[randomized controlled trial]]s, vortioxetine was among the lowest remission rates for generalized anxiety disorder of the included medications ([[odds ratio]] = 1.30 for vortioxetine, range of odds ratios for other agents = 1.13–2.70).<ref name="pmid33343351">{{cite journal | vauthors = Kong W, Deng H, Wan J, Zhou Y, Zhou Y, Song B, Wang X | title = Comparative Remission Rates and Tolerability of Drugs for Generalised Anxiety Disorder: A Systematic Review and Network Meta-analysis of Double-Blind Randomized Controlled Trials | journal = Front Pharmacol | volume = 11 | issue = | pages = 580858 | date = 2020 | pmid = 33343351 | pmc = 7741609 | doi = 10.3389/fphar.2020.580858 | doi-access = free | title-link = doi }}</ref>

Vortioxetine is [[contraindication|contraindicated]] in those taking [[monoamine oxidase inhibitor]]s (MAOIs), due to the possibility of [[serotonin syndrome]].<ref name="Trintellix FDA label" />

[[Sexual dysfunction]], such as [[decreased libido]], [[abnormal orgasm]], [[delayed ejaculation]], and [[erectile dysfunction]], are well-known side effects of SSRIs and [[serotonin–norepinephrine reuptake inhibitor]]s (SNRIs).<ref name="pmid25562777" /> In clinical trials, sexual dysfunction occurred more often with vortioxetine than with [[placebo]] and appeared to be dose-dependent.<ref name="pmid25562777" /><ref name="pmid25907797" /> The specific incidences{{verify spelling|date=September 2022|reason=''incidence'' is normally used only in the singular form, perhaps ''incidence'', ''incidents'', or ''instances'' was intended}}Incidence of treatment-emergent sexual dysfunction as measured with the [[Arizona Sexual Experience Scale]] (ASEX) were 14 to 20% for placebo and 16 to 34% for vortioxetine over a dosage range of 5 to 20&nbsp;mg/day.<ref name="pmid25562777" /><ref name="pmid25907797" /> The incidence of sexual dysfunction with vortioxetine was similar to that with the SNRI [[duloxetine]], which had an incidence of 26 to 28% at the used dosage of 60&nbsp;mg/day.<ref name="pmid25562777" /> However, treatment-emergent sexual dysfunction caused by a prior SSRI was better improved by switching to vortioxetine than by switching to the SSRI [[escitalopram]].<ref name="Trintellix FDA label" /> In another study, vortioxetine at a dosage of 10&nbsp;mg/day though not at 20&nbsp;mg/day produced less sexual dysfunction than the SSRI [[paroxetine]].<ref name="Trintellix FDA label" /> These findings suggest that although vortioxetine can still cause sexual dysfunction itself, it may cause somewhat less sexual dysfunction than SSRIs and might be a useful alternative option for people experiencing sexual dysfunction with these medications.<ref name="Trintellix FDA label" /><ref name="pmid29344340">{{cite journal | vauthors = Chokka PR, Hankey JR | title = Assessment and management of sexual dysfunction in the context of depression | journal = Ther Adv Psychopharmacol | volume = 8 | issue = 1 | pages = 13–23 | date = January 2018 | pmid = 29344340 | pmc = 5761906 | doi = 10.1177/2045125317720642 | url = }}</ref> The rates of voluntarily or spontaneously reported sexual dysfunction with vortioxetine are much lower than with the ASEX, ranging from <1 to 5% for vortioxetine versus <1 to 2% for placebo in clinical trials.<ref name="pmid25907797" /><ref name="pmid25562777" /><ref name="Trintellix FDA label" />

Based on preliminary clinical studies, vortioxetine may cause less [[reduced affect display|emotional blunting]] than SSRIs and SNRIs.<ref name="pmid33516560">{{cite journal | vauthors = Fagiolini A, Florea I, Loft H, Christensen MC | title = Effectiveness of Vortioxetine on Emotional Blunting in Patients with Major Depressive Disorder with inadequate response to SSRI/SNRI treatment | journal = Journal of Affective Disorders | volume = 283 | issue = | pages = 472–479 | date = March 2021 | pmid = 33516560 | pmc = | doi = 10.1016/j.jad.2020.11.106 | doi-access = free | title-link = doi | hdl = 11365/1137950 | hdl-access = free }}</ref><ref name="pmid28531820">{{cite journal | vauthors = Hughes S, Lacasse J, Fuller RR, Spaulding-Givens J | title = Adverse effects and treatment satisfaction among online users of four antidepressants | journal = Psychiatry Research | volume = 255 | issue = | pages = 78–86 | date = September 2017 | pmid = 28531820 | pmc = | doi = 10.1016/j.psychres.2017.05.021 | s2cid = 4572360 }}</ref>

In 2007, the compound was in [[Phases of clinical research|Phase II clinical trials]], and Lundbeck and [[Takeda Pharmaceutical Company|Takeda]] entered into a partnership in which Takeda paid Lundbeck $40 million up-front, with promises of up to $345 million in milestone payments, and Takeda agreed to pay most of the remaining cost of developing the drug. The companies agreed to co-promote the drug in the US and Japan, and that Lundbeck would receive a royalty on all such sales. The deal included another drug candidate, [[tedatioxetine]] (Lu AA24530), and could be expanded to include two other Lundbeck compounds.<ref>{{cite web | vauthors = Beaulieu D | work = First Word Pharma | date = 5 September 2007 | url = http://www.firstwordpharma.com/node/88051?tsid=17#axzz3xkIEA5eH | title = Lundbeck, Takeda enter strategic alliance for mood disorder, anxiety drugs | archive-url = https://web.archive.org/web/20161010215827/http://www.firstwordpharma.com/node/88051?tsid=17 | archive-date = 10 October 2016 }}</ref>

Vortioxetine was previously sold under the brand name Brintellix in the United States, but in May 2016, the US [[Food and Drug Administration]] (FDA) approved a name change to Trintellix in order to avoid confusion with the blood-thinning medication Brilinta ([[ticagrelor]]).<ref>{{Cite web|url=https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm498607.htm|title=Safety Alerts for Human Medical Products - Brintellix (vortioxetine): Drug Safety Communication - Brand Name Change to Trintellix, to Avoid Confusion With Antiplatelet Drug Brilinta (ticagrelor |publisher=U.S. [[Food and Drug Administration]] (FDA)|access-date=2 May 2016|url-status=dead|archive-url= https://web.archive.org/web/20160505122409/https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm498607.htm |archive-date=5 May 2016}}</ref> Other brand names include VantaxaTorvox, TorvoxVantaxa, Voxigain, and Trivoxetin,.<ref>{{cite etcweb|url=https://m.netmeds.com/generics/vortioxetine-10mg|title=Substitute Brands for Voxigain Tablet 10mg|website=Netmeds|access-date=31 August 2024}}</ref>

Vortioxetine was under development for the treatment of [[generalized anxiety disorder]]<ref name="pmid27050932">{{cite journal | vauthors = Orsolini L, Tomasetti C, Valchera A, Iasevoli F, Buonaguro EF, Vellante F, Fornaro M, Fiengo A, Mazza M, Vecchiotti R, Perna G, de Bartolomeis A, Martinotti G, Di Giannantonio M, De Berardis D | display-authors = 6 | title = New advances in the treatment of generalized anxiety disorder: the multimodal antidepressant vortioxetine | journal = Expert Review of Neurotherapeutics | volume = 16 | issue = 5 | pages = 483–95 | date = May 2016 | pmid = 27050932 | doi = 10.1586/14737175.2016.1173545 | s2cid = 4768865 }}</ref> and [[attention-deficit hyperactivity disorder]] (ADHD)<ref name="pmid30843450">{{cite journal | vauthors = Biederman J, Lindsten A, Sluth LB, Petersen ML, Ettrup A, Eriksen HF, Fava M | title = Vortioxetine for attention deficit hyperactivity disorder in adults: A randomized, double-blind, placebo-controlled, proof-of-concept study | journal = Journal of Psychopharmacology | volume = 33 | issue = 4 | pages = 511–521 | date = April 2019 | pmid = 30843450 | doi = 10.1177/0269881119832538 | s2cid = 73498106 }}</ref> but development for these indications was discontinued.<ref name="AdisInsight">{{cite web | title = Vortioxetine - Lundbeck | url = https://adisinsight.springer.com/drugs/800020088 | work = AdisInsight | publisher = Springer Nature Switzerland AG }}</ref> As of August 2021, vortioxetine remains in development for the treatment of [[anxiety disorder]]s, [[binge-eating disorder]], and [[bipolar disorder]].<ref name="AdisInsight" /> It is in [[Phases of clinical research#Phase II|phase II]] [[clinical trial]]s for these indications.<ref name="AdisInsight" /> There is also interest in vortioxetine for the potential treatment of [[social phobia]],<ref name="pmid29166552">{{cite journal | vauthors = Liebowitz MR, Careri J, Blatt K, Draine A, Morita J, Moran M, Hanover R | title = Vortioxetine versus placebo in major depressive disorder comorbid with social anxiety disorder | journal = Depression and Anxiety | volume = 34 | issue = 12 | pages = 1164–1172 | date = December 2017 | pmid = 29166552 | doi = 10.1002/da.22702 | s2cid = 37489812 | doi-access = free }}</ref> [[neuropathic pain]],<ref name="pmid34243960">{{cite journal | vauthors = Alcántara Montero A, Pacheco de Vasconcelos SR | title = Role of vortioxetine in the treatment of neuropathic pain | journal = Revista Espanola de Anestesiologia y Reanimacion | volume = | issue = | date = July 2021 | pmid = 34243960 | doi = 10.1016/j.redar.2021.04.001 | s2cid = 241004816 }}</ref> and for cognitive enhancement in major depression.<ref name="pmid31780961">{{cite journal | vauthors = Bennabi D, Haffen E, Van Waes V | title = Vortioxetine for Cognitive Enhancement in Major Depression: From Animal Models to Clinical Research | journal = Frontiers in Psychiatry | volume = 10 | issue = | pages = 771 | date = 2019 | pmid = 31780961 | pmc = 6851880 | doi = 10.3389/fpsyt.2019.00771 | doi-access = free | title-link = doi }}</ref>

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