Vortioxetine, sold under the trade names Trintellix and Brintellix, is an antidepressant medication that is used to treat depression. It increases serotonin concentrations in the brain by inhibiting its reuptake in the synapse, and by modulating (activating certain receptors while blocking, or antagonizing, others) certain serotonin receptors. This puts it in the class of atypical antidepressants known as serotonin modulators and stimulators. It is made by the pharmaceutical companies Lundbeck and Takeda.
|Trade names||Trintellix, Brintellix|
|By mouth (film-coated tablets)|
|Bioavailability||75% (peak at 7–11 hours)|
|Metabolism||Extensive hepatic, primarily CYP2D6-mediated oxidation|
|Elimination half-life||66 hours|
|Excretion||59% in urine, 26% in feces|
|Chemical and physical data|
|Molar mass||298.45 g/mol (379.36 as hydrobromide)|
|3D model (JSmol)|
|(what is this?)|
The most common side effects reported with vortioxetine are nausea, diarrhea, dry mouth, constipation, vomiting, flatulence, dizziness, and sexual dysfunction. However, with the exception of nausea, the risk of these side effects is less than 10% and up to 8% of patients taking placebos report the same side effects. Vortioxetine is considered a safe medicine for long term use in most people. However, as with all medicines in this class, if Vortioxetine is inappropriately prescribed alongside drugs with which it has interactions, then there is potential for the rare but potentially life-threatening drug reaction known as serotonin syndrome.
Incidence of sexual dysfunction is only slightly higher in patients taking vortioxetine than in people taking placebos and occurs in less than 10% of cases, and for this reason vortioxetine may be appropriate for people who have suffered sexual side effects from other antidepressant medicines in which the effects are more likely to occur.
|Ki (nM)||IC50 / EC50 (nM)||IA (%)|
* Human isoforms
Steady-state mean Cmax values were 9, 18, and 33 ng/mL following doses of 5, 10, and 20 mg/day. Steady-state plasma concentrations are typically reached within two weeks. It has no active metabolites (i.e., it is not a prodrug).
In 2007, the compound was in Phase II clinical trials, and Lundbeck and Takeda entered into a partnership in which Takeda paid Lundbeck $40 million upfront, 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.
Vortioxetine was previously trademarked as Brintellix in the United States, but on May 2, 2016, the US FDA approved a name change to Trintellix in order to avoid confusion with the blood-thinning medication Brilinta (ticagrelor).
Vortioxetine has been studied in several clinical settings as a potential treatment for generalized anxiety disorder. A 2015 Summary of clinical studies taking into account 4 studies none of which were randomized or blind found it has not been shown to be clinically beneficial for this application. Two 2017 randomized blind studies evaluating the efficacy of vortioxetine in GAD subjects who are working and/or pursuing an education concluded that "The beneficial effects of Vortioxetine on anxiety symptoms, functioning, and quality of life are greater in adults with GAD who are working and/or pursuing an education versus the full GAD study population.".
- "TGA eBS - Product and Consumer Medicine Information Licence". www.ebs.tga.gov.au. Archived from the original on 29 April 2018. Retrieved 29 April 2018.
- US Label Archived 2016-01-31 at the Wayback Machine. Last updated July 2014 after review in September, 2014. Versions of label are available at FDA index page Page accessed January 19, 2016
- Connolly, KR; Thase, ME (2016). "Vortioxetine: a New Treatment for Major Depressive Disorder". Expert Opinion on Pharmacotherapy. 17 (3): 421–31. doi:10.1517/14656566.2016.1133588. PMID 26679430.
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.
- Köhler S, Cierpinsky K, Kronenberg G, Adli M. The serotonergic system in the neurobiology of depression: Relevance for novel antidepressants. J Psychopharmacol. 2016 Jan;30(1):13-22. doi:10.1177/0269881115609072 PMID 26464458
- Kelliny M, Croarkin PE, Moore KM, Bobo WV. Profile of vortioxetine in the treatment of major depressive disorder: an overview of the primary and secondary literature. Ther Clin Risk Manag. 2015 Aug 12;11:1193-212. doi:10.2147/TCRM.S55313 PMID 26316764 Free full text Archived 2018-04-29 at the Wayback Machine.
- "Lundbeck's "Serotonin Modulator and Stimulator" Lu AA21004: How Novel? How Good? - GLG News". Archived from the original on 2011-07-24.
- Bang-Andersen B, Ruhland T, Jørgensen M, et al. (May 2011). "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. 54 (9): 3206–21. doi:10.1021/jm101459g. PMID 21486038.
- N. Moore; B. Bang-Andersen; L. Brennum; K. Fredriksen; S. Hogg; A. Mork; T. Stensbol; H. Zhong; C. Sanchez; D. Smith (August 2008). "Lu AA21004: a novel potential treatment for mood disorders". European Neuropsychopharmacology. 18 (Supplement 4): S321. doi:10.1016/S0924-977X(08)70440-1. Archived from the original on 2018-01-21.
- Sanchez, C; Asin, KE; Artigas, F (1 January 2015). "Vortioxetine, a Novel Antidepressant with Multimodal Activity: Review of Preclinical and Clinical Data". Pharmacology & Therapeutics. 145: 43–57. doi:10.1016/j.pharmthera.2014.07.001. ISSN 1879-016X. PMID 25016186. Retrieved 10 August 2016.
- Stahl, Stephen M. (2013-04-11). Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications (4th ed.). Cambridge University Press. ISBN 978-1107686465.
- "BindingDB Search: BDBM50400902 1-(2-(2,4-dimethylphenylsulfanyl)phenyl)piperazine". BindingDB. Retrieved 7 December 2018.
- "Australian Public Assessment Report for vortioxetine hydrobromide" (PDF). p. 11. Archived (PDF) from the original on 2017-08-01. Retrieved 2018-05-05.
- Sanchez, C; Asin, KE; Artigas, F (2015). "Vortioxetine, a novel antidepressant with multimodal activity: review of preclinical and clinical data". Pharmacol. Ther. 145: 43–57. doi:10.1016/j.pharmthera.2014.07.001. PMID 25016186.
- Daniel Beaulieu for First Word Pharma. September 5th, 2007 Lundbeck, Takeda enter strategic alliance for mood disorder, anxiety drugs Archived 2016-10-10 at the Wayback Machine.
- FDA approves new drug to treat major depressive disorder Archived 2013-10-03 at the Wayback Machine., U.S. Food and Drug Administration Press Announcement.
- EMA Brintellix page at EMA site Archived 2016-01-26 at the Wayback Machine. Page accessed January 19, 2016
- Commissioner, Office of the. "Safety Alerts for Human Medical Products - Brintellix (vortioxetine): Drug Safety Communication - Brand Name Change to Trintellix, to Avoid Confusion With Antiplatelet Drug Brilinta (ticagrelor)". www.fda.gov. Archived from the original on 2016-05-05. Retrieved 2016-05-02.
- Fu, Jie; Peng, Lilei; Li, Xiaogang (2016-04-19). "The efficacy and safety of multiple doses of vortioxetine for generalized anxiety disorder: a meta-analysis". Neuropsychiatric Disease and Treatment. 12: 951–959. doi:10.2147/NDT.S104050. ISSN 1176-6328. PMC 4844447. PMID 27143896.
- Christensen, M. C.; Loft, H.; Florea, I.; McIntyre, R. S. (2017). "Efficacy of vortioxetine in working patients with generalized anxiety disorder". Cns Spectrums: 1–9. doi:10.1017/S1092852917000761. PMID 29081307.
- "Efficacy and Safety of Vortioxetine (Lu AA21004) for Treatment of Generalized Anxiety Disorder in Adults".
- "Relapse-prevention Study With Lu AA21004 (Vortioxetine) in Patients With Generalized Anxiety Disorder".