Vortioxetine
 | |
 | |
| Clinical data | |
|---|---|
| Pronunciation | vor-tee-OX-uh-teen |
| Trade names | Trintellix, Brintellix |
| Other names | Lu AA21004 |
| License data |
|
| Routes of administration | Oral (film-coated tablets) |
| ATC code | |
| Legal status | |
| Legal status | |
| Pharmacokinetic data | |
| Bioavailability | 75% (peak at 7–11 hours) |
| Protein binding | 98% |
| Metabolism | extensive hepatic, primarily CYP2D6-mediated oxidation |
| Elimination half-life | 66 hours |
| Excretion | 59% in urine, 26% in feces |
| Identifiers | |
| |
| CAS Number | |
| PubChem CID | |
| IUPHAR/BPS | |
| ChemSpider | |
| KEGG | |
| ChEBI | |
| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.258.748 |
| Chemical and physical data | |
| Formula | C18H22N2S |
| Molar mass | 298.45 g/mol (379.36 as hydrobromide) g·mol−1 |
| 3D model (JSmol) | |
| |
| |
  (what is this?) (verify) | |
Vortioxetine (trade names Trintellix, Brintellix) is an atypical antidepressant (a serotonin modulator and stimulator) made by Lundbeck and Takeda.[2]
Medical use
Vortioxetine is used as first-line treatment for major depressive disorder.[2][3][4][5][6]
Side effects
The most common side effects reported with vortioxetine are nausea, diarrhea, dry mouth, constipation, vomiting, flatulence, dizziness, and sexual dysfunction.[2] 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.[2]
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[2][6]
Pharmacodynamics
Vortioxetine is a so-called "serotonin modulator and stimulator".Cite error: The <ref> tag has too many names (see the help page). It has been shown to possess the following pharmacological actions:[2][7][8][9]
| Target | Affinity | Functional activity | |
| Ki, (nM) | IC50 / EC50 (nM) | IA (%) | |
| SERT* | 1,6 | 5,4 | — |
| 5-HT1A* | 15 | 200 | 96 |
| 5-HT1B* | 33 | 120 | 55 |
| 5-HT1D* | 54 | 370 | — |
| 5-HT3* | 3,7 | 12 | — |
| 5-HT7* | 19 | 450 | — |
| β1-adrenoceptor | 46[7] | — | — |
* 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.[2] It has no active metabolites (i.e. it is not a prodrug).[2]
Research
Vortioxetine has been studied in several clinical trials as a potential treatment for generalized anxiety disorder but results were inconsistent.[10][11]
History
Vortioxetine was discovered by scientists at Lundbeck who reported the rationale and synthesis for the drug (then called Lu AA21004) in a 2011 paper.[7][12]
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.[13]
Vortioxetine was approved by the U.S. FDA for the treatment of major depressive disorder (MDD) in adults in September, 2013,[14] and it was approved in Europe later that year.[15]
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).[16]
See also
- Tedatioxetine
- Vilazodone, an antidepressant with a similar dual mechanism of action
References
- ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
- ^ a b c d e f g h 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
- ^ [No authors listed] Vortioxetine. Aust Prescr. 2015 Jun;38(3):101-2. PMID 26648632 Free full text
- ^ "Relative efficacy and tolerability of vortioxetine versus selected antidepressants by indirect comparisons of similar clinical studies". Curr Med Res Opin. 30: 2589–606. Oct 10, 2014. doi:10.1185/03007995.2014.969566. PMID 25249164.
- ^ 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
- ^ a b 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
- ^ a b c 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.
- ^ 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
- ^ 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.