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Vortioxetine

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Vortioxetine
Clinical data
Other namesLu AA21004
Routes of
administration		Oral
ATC code
  • None
Legal status
Legal status
Identifiers
  • 1-(2-((2,4-dimethylphenyl)thio)phenyl)piperazine
CAS Number
PubChem CID
ChemSpider
KEGG
CompTox Dashboard (EPA)
ECHA InfoCard100.258.748 Edit this at Wikidata
Chemical and physical data
FormulaC18H22N2S
Molar mass298.45 g/mol g·mol−1
3D model (JSmol)
  • CC(C=C(C)C=C1)=C1SC2=C(N3CCNCC3)C=CC=C2
  • InChI=1S/C18H22N2S/c1-14-7-8-17(15(2)13-14)21-18-6-4-3-5-16(18)20-11-9-19-10-12-20/h3-8,13,19H,9-12H2,1-2H3
  • Key:YQNWZWMKLDQSAC-UHFFFAOYSA-N
  (verify)

Vortioxetine (vor-tye-ox-e-teen, code name Lu AA21004) is an experimental drug currently under development by Lundbeck and Takeda for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD).[2] Commercial names chosen are Brintellix and Rexulti.

Regulatory approval for the treatment of MDD for the European market has been filed in September 2012, for the United States in October 2012, and filing for Canada should follow. Filing for the Japanese market is expected in 2013.[3][4]

Efficacy

Depression

In May 2011, Lundbeck presented the results of four phase III trials on vortioxetine at the 2011 Annual Meeting of the American Psychiatric Association. A statistically significant effect was shown in two of the studies (one for active treatment using the Hamilton Depression Rating Scale (HAM-D), the second as a maintenance treatment), vortioxetine failed to prove superiority over placebo in a third (again using the HAM-D) and the fourth was nullified by an exceptionally high placebo response (according to the Montgomery-Åsberg Depression Rating Scale (MADRS)).[5]

In July 2011, Lundbeck published the results of a double-blind, randomized, placebo-controlled clinical trial with venlafaxine as an active reference. It was found to be superior to placebo in treating MDD while having fewer side effects than venlafaxine.[6] Similarly, in May 2012, Lundbeck published the results of a double-blind, randomized, placebo-controlled clinical trial with duloxetine evaluating vortioxetine in elderly depressed patients, and it was found superior to placebo, with fewer side effects than duloxetine.[7]

In May 2012, Lundbeck disclosed the results of three phase III clinical trials, showing vortioxetine's superiority over placebo according to the MADRS.[8]

In August 2012, a randomized, double-blind trial confirms the superiority of vortioxetine over placebo according to all measures, excepted the Sheehan Disability scale.[9]

In September 2012, a randomised, double-blind trial reveals that a dose of 5mg shows superiority over placebo only in patients that suffer from comorbid anxiety.[10] This is consistent with results from another trial published in December 2012, demonstrating that 2.5 mg and 5 mg doses are ineffective.[11]

Anxiety

August 2012, contradictory results of two randomized, double-blind trial were published. While the first demonstrated vortioxetine's superiority over the placebo,[12] the second showed that the drug had no efficacy, leading the authors to question the designs of the different trials.[13]

Other effects

In an article published in February 2013, Lundbeck scientists report that vortioxetine enhances some forms of memory in rats.[14]

Side effects

The most common side effects reported with vortioxetine are nausea, vomiting, diarrhea, headache, and dizziness.[8][5][7]

Incidence of sexual dysfunction is reportedly lower than with venlafaxine.[6]

Pharmacology

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:[15][16]

Vortioxetine also has affinity for the β1-adrenergic receptor (Ki = 46 nM), though any actions at this site are unlikely to contribute to its therapeutic effects and likely only to contribute to side effects.[15]

Controversies

Concerns have been raised as to why Lundbeck are trialing vortioxetine alongside drugs such as venlafaxine (well known for its side effects) and not other drugs like escitalopram (which has a lower side effect profile and which Lundbeck promotes as its most effective treatment for depressive disorders). Reasons for this have been proposed as being due to the fact that the patent for escitalopram expires 2012, meaning that the company will need a new drug to promote and sell in order to remain financially competitive.[citation needed]

See also

References

  1. ^ "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.
  2. ^ Jancin B (2009). "Lu AA21004 Looks Promising for Depression". Clinical Psychiatry News. 37 (12): 24–25. doi:10.1016/S0270-6644(09)70441-2. {{cite journal}}: Unknown parameter |month= ignored (help)
  3. ^ http://uk.reuters.com/article/2012/09/20/us-lundbeck-vortioxetine-idUKBRE88J09620120920?feedType=RSS&feedName=healthNews
  4. ^ http://www.reuters.com/article/2012/10/02/markets-nordics-factors-idUSL6E8L20VJ20121002?type=marketsNews
  5. ^ a b http://investor.lundbeck.com/releasedetail.cfm?ReleaseID=608559
  6. ^ a b Alvarez E, Perez V, Dragheim M, Loft H, Artigas F (2011). "A double-blind, randomized, placebo-controlled, active reference study of Lu AA21004 in patients with major depressive disorder". The International Journal of Neuropsychopharmacology / Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum (CINP). 15 (5): 1–12. doi:10.1017/S1461145711001027. PMC 3349292. PMID 21767441. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  7. ^ a b Katona C, Hansen T, Olsen Ck (2012). "A randomized, double-blind, placebo-controlled, duloxetine-referenced, fixed-dose study comparing the efficacy and safety of Lu AA21004 in elderly patients with major depressive disorder". International clinical psychopharmacology. 27 (4): 215–23. doi:10.1097/YIC.0b013e3283542457. PMID 22572889. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  8. ^ a b http://www.fiercebiotech.com/press-releases/statistically-significant-clinical-phase-iii-results-lu-aa21004-provide-bas
  9. ^ Henigsberg N, Mahableshwarkar AR, Jacobsen P, Chen Y, Thase ME (2012). "A randomized, double-blind, placebo-controlled 8-week trial of the efficacy and tolerability of multiple doses of Lu AA21004 in adults with major depressive disorder". J Clin Psychiatry. 73 (7): 953–9. doi:10.4088/JCP.11m07470. PMID 22901346. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  10. ^ Jain R, Mahableshwarkar AR, Jacobsen PL, Chen Y, Thase ME (2012). "A randomized, double-blind, placebo-controlled 6-wk trial of the efficacy and tolerability of 5 mg vortioxetine in adults with major depressive disorder". Int. J. Neuropsychopharmacol.: 1–9. doi:10.1017/S1461145712000727. PMID 22963932. {{cite journal}}: Unknown parameter |month= ignored (help); no-break space character in |title= at position 96 (help)CS1 maint: multiple names: authors list (link)
  11. ^ Mahableshwarkar AR, Jacobsen PL, Chen Y (2012). "A Randomized, Double-Blind Trial of 2.5 mg and 5 mg Vortioxetine (Lu AA21004) Versus Placebo for 8 Weeks in Adults With Major Depressive Disorder". Curr Med Res Opin. doi:10.1185/03007995.2012.761600. PMID 23252878. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  12. ^ Henigsberg N, Mahableshwarkar AR, Jacobsen P, Chen Y, Thase ME (13 August 2012). "A randomized, double-blind, placebo-controlled 8-week trial of the efficacy and tolerability of multiple doses of lu aa21004 in adults with major depressive disorder". European neuropsychopharmacology. PMID 22898365.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  13. ^ Rothschild AJ, Mahableshwarkar AR, Jacobsen P, Yan M, Sheehan DV (14 August 2012). "Vortioxetine (Lu AA21004) 5mg in generalized anxiety disorder: Results of an 8-week randomized, double-blind, placebo-controlled clinical trial in the United States". European neuropsychopharmacology. PMID 22901736.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  14. ^ Mørk A, Montezinho LP, Miller S, Trippodi-Murphy C, Plath N, Li Y, Gulinello M, Sanchez C (1 February 2013). "Vortioxetine (Lu AA21004), a novel multimodal antidepressant, enhances memory in rats". Pharmacology, biochemistry, and behavior. PMID 23380522.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  15. ^ a b Bang-Andersen B, Ruhland T, Jørgensen M; et al. (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. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  16. ^ N. Moore; B. Bang-Andersen; L. Brennum; K. Fredriksen; S. Hogg; A. Mork; T. Stensbol; H. Zhong; C. Sanchez; D. Smith (2008). "Lu AA21004: a novel potential treatment for mood disorders". European Neuropsychopharmacology. 18 (Supplement 4): S321. doi:10.1016/S0924-977X(08)70440-1. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
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