Vortioxetine

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Vortioxetine
Vortioxetine.svg
Vortioxetine ball-and-stick model.png
Clinical data
Pronunciation /vɔːrtiːˈoʊksətiːn/ vor-tee-OX-uh-teen
Trade names Trintellix, Brintellix
License data
Pregnancy
category
  • US: C (Risk not ruled out)
Routes of
administration		 By mouth (film-coated tablets)
ATC code
Legal status
Legal status
  • In general: ℞ (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
Synonyms Lu AA21004
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
Chemical and physical data
Formula C18H22N2S
Molar mass 298.45 g/mol (379.36 as hydrobromide)
3D model (Jmol)
 NYesY (what is this?)  (verify)

Vortioxetine (trade names Trintellix, Brintellix) is an atypical antidepressant (a serotonin modulator and stimulator) made by Lundbeck and Takeda.[1]

Medical uses[edit]

Vortioxetine is used as a treatment for major depressive disorder.[1][2][3][4]

Adverse effects[edit]

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[edit]

Pharmacodynamics[edit]

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[edit]

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[edit]

10mg tablets of brand-name vortioxetine (Trintellix, formerly known as Brintellix).

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[edit]

Vortioxetine has been studied in several clinical trials as a potential treatment for generalized anxiety disorder but results were inconsistent.[15][16]

See also[edit]

References[edit]

  1. ^ 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
  2. ^ 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. 
  3. ^ 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
  4. ^ 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. doi:10.2147/TCRM.S55313 PMID 26316764 Free full text
  5. ^ "Lundbeck's "Serotonin Modulator and Stimulator" Lu AA21004: How Novel? How Good? - GLG News". 
  6. ^ 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. 
  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. ^ 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. 
  9. ^ Stahl, Stephen M. Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications (4th ed.). Cambridge University Press. ISBN 978-1107686465. 
  10. ^ 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. 
  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. 
  15. ^ Pae, CU; et al. (May 2015). "Vortioxetine, a multimodal antidepressant for generalized anxiety disorder: a systematic review and meta-analysis". J Psychiatr Res. 64: 88–98. doi:10.1016/j.jpsychires.2015.02.017. PMID 25851751. 
  16. ^ Reinhold JA, Rickels K. Pharmacological treatment for generalized anxiety disorder in adults: an update. Expert Opin Pharmacother. 2015;16(11):1669-81. PMID 26159446
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