Vortioxetine
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Clinical data | |
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Pronunciation | vor-tee-OX-uh-teen |
Trade names | Trintellix, Brintellix |
License data |
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Pregnancy category |
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Routes of administration | By mouth (film-coated tablets) |
ATC code | N06AX26 (WHO) |
Legal status | |
Legal status |
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Pharmacokinetic data | |
Bioavailability | 75% (peak at 7–11 hours) |
Protein binding | 98% |
Metabolism | Extensive hepatic, primarily CYP2D6-mediated oxidation |
Biological half-life | 66 hours |
Excretion | 59% in urine, 26% in feces |
Identifiers | |
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Synonyms | Lu AA21004 |
CAS Number |
508233-74-7 ![]() |
PubChem (CID) | 9966051 |
IUPHAR/BPS | 7351 |
DrugBank |
DB09068 ![]() |
ChemSpider |
8141643 ![]() |
UNII |
3O2K1S3WQV ![]() |
KEGG |
D10184 ![]() |
ChEBI |
CHEBI:76016 ![]() |
Chemical and physical data | |
Formula | C18H22N2S |
Molar mass | 298.45 g/mol (379.36 as hydrobromide) |
3D model (Jmol) | Interactive image |
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Vortioxetine (trade names Trintellix, Brintellix) is an atypical antidepressant (a serotonin modulator and stimulator) made by Lundbeck and Takeda.[1]
Medical uses
Vortioxetine is used as a treatment for major depressive disorder.[1][2][3][4]
Adverse effects
The most common side effects reported with vortioxetine are nausea, diarrhea, dry mouth, constipation, vomiting, flatulence, dizziness, and sexual dysfunction.[1] Vortioxetine used alone in high dose or in combination with other medications, such as other antidepressants, can produce a potentially life-threatening drug reaction known as serotonin syndrome.[1]
Incidence of sexual dysfunction is reportedly higher in patients taking vortioxetine than in people taking placebos but appears to be lower than in people taking other antidepressants[1][4]
Pharmacology
Pharmacodynamics
Vortioxetine is a so-called "serotonin modulator and stimulator".[5] It has been shown to possess the following pharmacological actions:[1][6][7][8][9]
Target | Affinity | Functional activity | Pharmacodynamic action | |
Ki (nM) | IC50 / EC50 (nM) | IA (%) | ||
SERT* | 1.6 | 5.4 | — | Inhibition |
NET* | 113 | — | — | Inhibition |
5-HT1A* | 15 | 200 | 96 | Agonist |
5-HT1B* | 33 | 120 | 55 | Partial agonist |
5-HT1D* | 54 | 370 | — | Antagonist |
5-HT3* | 3.7 | 12 | — | Antagonist |
5-HT7* | 19 | 450 | — | Antagonist |
β1-adrenoceptor | 46[6] | — | — | — |
* Human isoforms
Pharmacokinetics
Vortioxetine reaches peak plasma concentration (Cmax) within 7 to 11 hours post-administration (Tmax), and its mean terminal half-life ( T⁄1/2) is ≈ 66 hours. Steady-state plasma concentrations are typically reached within two weeks.[1] It has no active metabolites (i.e. it is not a prodrug).[1]
History
![](../I/m/Trintellix_10mg_tablets.png)
Vortioxetine was discovered by scientists at Lundbeck who reported the rationale and synthesis for the drug (then called Lu AA21004) in a 2011 paper.[6][10]
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.[11]
Vortioxetine was approved by the U.S. FDA for the treatment of major depressive disorder (MDD) in adults in September 2013,[12] and it was approved in Europe later that year.[13]
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).[14]
Research
Vortioxetine has been studied in several clinical trials as a potential treatment for generalized anxiety disorder but results were inconsistent.[15][16]
See also
- Tedatioxetine
- Vilazodone, an antidepressant with a similar dual mechanism of action
References
- 1 2 3 4 5 6 7 8 US Label 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. 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. PMID 26464458
- 1 2 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. PMID 26316764 Free full text
- ↑ "Lundbeck's "Serotonin Modulator and Stimulator" Lu AA21004: How Novel? How Good? - GLG News".
- 1 2 3 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.
- ↑ 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. Retrieved 10 August 2016.
- ↑ Stahl, Stephen M. Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications (4th edition ed.). Cambridge University Press. ISBN 978-1107686465.
- ↑ Sanchez C, Asin KE, Artigas F Vortioxetine, a novel antidepressant with multimodal activity: review of preclinical and clinical data. Pharmacol Ther. 2015 Jan;145:43-57. PMID 25016186 Free full text
- ↑ Daniel Beaulieu for First Word Pharma. September 5th, 2007 Lundbeck, Takeda enter strategic alliance for mood disorder, anxiety drugs
- ↑ FDA approves new drug to treat major depressive disorder, U.S. Food and Drug Administration Press Announcement.
- ↑ EMA Brintellix page at EMA site 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. Retrieved 2016-05-02.
- ↑ Pae CU et al. Vortioxetine, a multimodal antidepressant for generalized anxiety disorder: a systematic review and meta-analysis. J Psychiatr Res. 2015 May;64:88-98. PMID 25851751
- ↑ Reinhold JA, Rickels K. Pharmacological treatment for generalized anxiety disorder in adults: an update. Expert Opin Pharmacother. 2015;16(11):1669-81. PMID 26159446