|Trade names||Trintellix, Brintellix, others|
|Other names||Lu AA21004|
|By mouth (film-coated tablets)|
|Bioavailability||75% (peak at 7–11 hours)|
|Metabolism||Extensive Liver, primarily CYP2D6-mediated oxidation|
|Elimination half-life||66 hours|
|Excretion||59% in urine, 26% in feces|
|CompTox Dashboard (EPA)|
|Chemical and physical data|
|Molar mass||298.45 g·mol−1|
|3D model (JSmol)|
|(what is this?)|
Vortioxetine, sold under the brand names Trintellix and Brintellix among others, is a medication used to treat major depressive disorder. Effectiveness is viewed as similar to that of other antidepressants. In the United Kingdom, it is only recommended in people who have not improved sufficiently on two other antidepressants. It is taken by mouth.
Common side effects include constipation and nausea. Serious side effects may include suicide in those under the age of 25, serotonin syndrome, bleeding, mania, and SIADH. Vortioxetine may cause less emotional blunting than typical SSRIs and SNRIs. A withdrawal syndrome may occur if the dose is rapidly decreased. Use during pregnancy and breastfeeding is not generally recommended. It is classified as a serotonin modulator. How it works is not entirely clear but is believed to be related to increasing serotonin levels.
Vortioxetine is used as a treatment for major depressive disorder. Effectiveness appear to be similar to other antidepressants. It may be used when other treatments have failed. A 2017 Cochrane review on vortioxetine determined that the place for it in the treatment of severe depression is unclear due to low quality evidence and that more study is needed comparing vortioxetine to SSRIs which are typical first line treatments.
Vortioxetine is also used off-label for anxiety. 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). A 2019 meta-analysis found that vortioxetine didn't produce statistically significant results over the placebo in the symptoms, quality of life and remission rates of the generalised anxiety disorder, but it was well tolerated.
The most common side effects reported with vortioxetine are nausea, diarrhea, dry mouth, constipation, vomiting, flatulence, dizziness, and sexual dysfunction. However, with the singular exception of nausea, these side effects occurred in less than 10% of study participants given the active drug, with up to 8% of placebo-treated participants reporting the same side effects.
If vortioxetine is prescribed alongside traditional selective serotonin reuptake inhibitors (SSRIs), or other serotonergic drugs, this can induce the potentially life-threatening 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 vortioxetine-treated patients. As such, vortioxetine may be appropriate for people who have suffered sexual side effects from other antidepressant medications.
Vortioxetine 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 serotonin modulators and stimulators which also includes vilazodone. It has been shown to possess the following pharmacological actions:
|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.
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 approved by the U.S. Food and Drug Administration (FDA) for the treatment of major depressive disorder (MDD) in adults in September 2013, and it was approved in Europe later that year.
Society and culture
Vortioxetine was previously sold under the brand name 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).
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- "Brintellix EPAR". European Medicines Agency (EMA). Retrieved 15 January 2021.
- "Vortioxetine Hydrobromide Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 18 March 2019.
- British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 376. ISBN 9780857113382.
- Fagiolini A, Florea I, Loft H, Christensen MC (2021). "Effectiveness of Vortioxetine on Emotional Blunting in Patients with Major Depressive Disorder with inadequate response to SSRI/SNRI treatment". J Affect Disord. 283: 472–479. doi:10.1016/j.jad.2020.11.106. PMID 33516560.CS1 maint: multiple names: authors list (link)
- Hughes S, Lacasse J, Fuller RR, Spaulding-Givens J (2017). "Adverse effects and treatment satisfaction among online users of four antidepressants". Psychiatry Res. 255: 78–86. doi:10.1016/j.psychres.2017.05.021. PMID 28531820.CS1 maint: multiple names: authors list (link)
- "Vortioxetine Hydrobromide - Drug Usage Statistics". ClinCalc. Retrieved 11 April 2020.
- Long, JoAnn D. (2019-06-21). "Vortioxetine for Depression in Adults". Issues in mental health nursing. Informa UK Limited. 40 (9): 819–820. doi:10.1080/01612840.2019.1604920. ISSN 0161-2840. PMID 31225773.
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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, Stephan; Cierpinsky, Katharina; Kronenberg, Golo; Adli, Mazda (2016). "The serotonergic system in the neurobiology of depression: Relevance for novel antidepressants". Journal of Psychopharmacology. 30 (1): 13–22. doi:10.1177/0269881115609072. PMID 26464458. S2CID 21501578.
- Bobo, William; Kelliny, Marc; Croarkin, Paul; Moore, Katherine (2015). "Profile of vortioxetine in the treatment of major depressive disorder: An overview of the primary and secondary literature". Therapeutics and Clinical Risk Management. 11: 1193–212. doi:10.2147/TCRM.S55313. PMC 4542474. PMID 26316764.
- Koesters, Markus; Ostuzzi, Giovanni; Guaiana, Giuseppe; Breilmann, Johanna; Barbui, Corrado (2017-07-05). "Vortioxetine for depression in adults". The Cochrane Database of Systematic Reviews. 7: CD011520. doi:10.1002/14651858.CD011520.pub2. ISSN 1469-493X. PMC 6483322. PMID 28677828.
- Pae, Chi-Un; Wang, Sheng-Min; Han, Changsu; Lee, Soo-Jung; Patkar, Ashwin A.; Masand, Praksh S.; Serretti, Alessandro (May 2015). "Vortioxetine, a multimodal antidepressant for generalized anxiety disorder: a systematic review and meta-analysis". Journal of Psychiatric Research. 64: 88–98. doi:10.1016/j.jpsychires.2015.02.017. ISSN 1879-1379. PMID 25851751.
- 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.
- Qin, Bin; Huang, Guangsu; Yang, Qian; Zhao, Mingjun; Chen, Hong; Gao, Wen; Yang, Mingxiu (November 2019). "Vortioxetine treatment for generalised anxiety disorder: a meta-analysis of anxiety, quality of life and safety outcomes". BMJ Open. 9 (11): e033161. doi:10.1136/bmjopen-2019-033161. PMC 6924794. PMID 31784448.
- "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. S2CID 54253895.
- 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.
- 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.