TRINTELLIX® (vortioxetine) is indicated for the treatment of Major Depressive Disorder (MDD) in adults.

Patient portrayal. 
Individual results may vary.

MOA

The story of TRINTELLIX

The first and only compound with this combination of pharmacologic activity:

Mechanism of action1

The mechanism of the antidepressant effect of TRINTELLIX is not fully understood, but it is thought to be related to its enhancement of serotonergic activity in the central nervous system through inhibition of the reuptake of serotonin (5-HT). It also has several other activities including 5-HT3 receptor antagonism and 5-HT1A receptor agonism. The contribution of these activities to the antidepressant effect of TRINTELLIX has not been established.

Pharmacodynamics1

TRINTELLIX strongly inhibits SERT and has strong affinities for 5 other serotonin receptors.* The clinical relevance of these activities is unknown.

TRINTELLIX (vortioxetine) Mechanism of Action (MOA)

*TRINTELLIX binds with high affinity to the human serotonin transporter (Ki=1.6 nM), but not to the norepinephrine (Ki=113 nM) or dopamine (Ki>1000 nM) transporters.1 TRINTELLIX potently and selectively inhibits reuptake of serotonin (IC50=5.4 nM). TRINTELLIX binds to 5-HT3 (Ki=3.7 nM), 5-HT1A (Ki=15 nM), 5-HT7 (Ki=19 nM), 5-HT1D (Ki=54 nM), and 5-HT1B (Ki=33 nM) receptors, and is a 5-HT3, 5-HT1D, and 5-HT7 receptor antagonist, 5-HT1B receptor partial agonist, and 5-HT1A receptor agonist.

Abbrevation: SERT, serotonin transporter.

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  1. Trintellix (vortioxetine) prescribing information. Takeda Pharmaceuticals.
  2. Alvarez E, Perez V, Dragheim M, Loft H, Artigas F. A double-blind, randomized, placebo-controlled, active reference study of LuAA21004 in patients with Major Depressive Disorder. Int J Neuropsychopharmacol. 2012;15(5):589-600.
  3. Henigsberg N, Mahableshwarkar AR, Jacobsen P, Chen Y, Thase ME. 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. 2012;73(7):953-959.
  4. Boulenger J-P, Loft H, Olsen CK. Efficacy and safety of vortioxetine (Lu AA21004), 15 and 20 mg/day: a randomized, double-blind, placebo-controlled, duloxetine-referenced study in the acute treatment of adult patients with Major Depressive Disorder. Int Clin Psychopharmacol. 2014;29(3):138-149.
  5. Mahableshwarkar AR, Jacobsen P, Chen Y, Serenko M, Trivedi MH. A randomized, double-blind, duloxetine‑referenced study comparing efficacy and tolerability of 2 fixed doses of vortioxetine in the acute treatment of adults with MDD. Psychopharmacology (Berl). 2015;232(12):2061-2070.
  6. Jacobsen P, Mahableshwarkar AR, Serenko M, Chan S, Trivedi MH. A randomized, double-blind, placebo-controlled study of the efficacy and safety of vortioxetine 10 mg and 20 mg in adults with Major Depressive Disorder. J Clin Psychiatry. 2015;76(5):575-582.
  7. Katona C, Hansen T, Olsen CK. 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. Int Clin Psychopharmacol. 2012;27(4):215-223.
  8. McIntyre RS, Lophaven S, Olsen CK. A randomized, double-blind, placebo-controlled study of vortioxetine on cognitive function in depressed adults. Int J Neuropsychopharmacol. 2014;17(10):1557-1567.
  9. Mahableshwarkar AR, Zajecka J, Jacobson W, Chen Y, Keefe RSE. A randomized, placebo-controlled, active-reference, double-blind, flexible-dose study of the efficacy of vortioxetine on cognitive function in Major Depressive Disorder. Neuropsychopharmacology. 2015;40(8):2025-2037.
  10. Data on file. Takeda Pharmaceuticals.
  11. Data on file. Lundbeck.
  12. Boulenger J-P, Loft H, Florea I. A randomized clinical study of Lu AA21004 in the prevention of relapse in patients with Major Depressive Disorder. J Psychopharmacol. 2012;26(11):1408-1416.
  13. Jacobsen PL, Mahableshwarkar AR, Chen Y, Chrones L, Clayton AH. Effect of vortioxetine vs. escitalopram on sexual functioning in adults with well‑treated Major Depressive Disorder experiencing SSRI-induced sexual dysfunction. J Sex Med. 2015;12(10):2036-2048.
  14. Kambeitz JP, Howes OD. The serotonin transporter in depression: Meta-analysis of in vivo and post mortem findings and implications for understanding and treating depression. J Affect Disord. 2015;186:358-366.
  15. American Psychiatric Association. Depressive disorders. In: Diagnostic and Statistical Manual of Mental Disorders. 5th edition (DSM-5®). Arlington, VA: American Psychiatric Association; 2013:155-188.
  16. ICD-10-CM Tabular list of diseases and injuries. Centers for Medicare & Medicaid Services. Published 2022. https://www.cms.gov/files/zip/2022-code-tables-tabular-and-index-updated-02012022.zip. Accessed August 19, 2022.