Vortioxetine

Vortioxetine
Systematic (IUPAC) name
1-[2-(2,4-Dimethyl-phenylsulfanyl)-phenyl]piperazine
Clinical data
Trade names Trintellix, Brintellix
License data
Pregnancy
category
  • US: C (Risk not ruled out)
Routes of
administration		 Oral
Legal status
Legal status
  • â„ž (Prescription only)
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
CAS Number 508233-74-7 YesY
ATC code N06AX26 (WHO)
PubChem CID 9966051
IUPHAR/BPS 7351
ChemSpider 8141643 N
KEGG D10184 N
ChEBI CHEBI:76016 N
Synonyms Lu AA21004
Chemical data
Formula C18H22N2S
Molar mass 298.45 g/mol (379.36 as hydrobromide)
 NYesY (what is this?)  (verify)

Vortioxetine (vor-tye-OKS-e-teen, trade name Trintellix) is an atypical antidepressant (a serotonin modulator and stimulator) made by Lundbeck and Takeda.[1]

Medical use

Vortioxetine is used as first-line treatment for major depressive disorder.[1][2][3][4][5]

Side 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][5]

Pharmacodynamics

Vortioxetine is a so-called "serotonin modulator and stimulator".<ref name="urlLundbeck's "Serotonin Modulator and Stimulator" Lu AA21004: How Novel? How Good? - GLG News">"Lundbeck's "Serotonin Modulator and Stimulator" Lu AA21004: How Novel? How Good? - GLG News". </ref> It has been shown to possess the following pharmacological actions:[1][6][7]

Pharmacokinetics

Vortioxetine reaches peak plasma concentration (Cmax) within 7 to 11 hours post-administration (Tmax), and its mean terminal half-life (t½) 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]

Research

Vortioxetine has been studied in several clinical trials as a potential treatment for general anxiety disorder but results were inconsistent.[8][9]

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.[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 ticagrelor (Brilinta).[14]

See also

References

  1. 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
  2. ↑ [No authors listed] Vortioxetine. Aust Prescr. 2015 Jun;38(3):101-2. PMID 26648632 Free full text
  3. ↑ "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.
  4. ↑ 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
  5. 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
  6. 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.
  7. ↑ 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.
  8. ↑ 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
  9. ↑ Reinhold JA, Rickels K. Pharmacological treatment for generalized anxiety disorder in adults: an update. Expert Opin Pharmacother. 2015;16(11):1669-81. PMID 26159446
  10. ↑ 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
  11. ↑ Daniel Beaulieu for First Word Pharma. September 5th, 2007 Lundbeck, Takeda enter strategic alliance for mood disorder, anxiety drugs
  12. ↑ FDA approves new drug to treat major depressive disorder, U.S. Food and Drug Administration Press Announcement.
  13. ↑ EMA Brintellix page at EMA site Page accessed January 19, 2016
  14. ↑ 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.
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