Vortioxetine (Trintellix/Brintillex)

Vortioxetine (Trade name: Trintellix/Brintillex) is an antidepressant in the serotonin modulator and stimulator class used in the treatment of major depressive disorder.

Pharmacokinetics of Vortioxetine

Vortioxetine: Cytochrome P450 Metabolism

Substrate of (Metabolized by)
  • Similar vilazodone, vortioxetine acts like an SSRI but also has direct serotonin receptor interactions that is thought to theoretically add to its clinical benefit. It has the following actions:
  • Serotonin (5-HT) transporter (SERT) inhibition
    • This is also the primary mechanism of action of classic antidepressants like SSRIs and SNRIs.
  • Serotonin (5-HT) receptor agonism:
    • 5-HT1A agonism
      • Which theoretically can enhance downregulation of presynaptic 5-HT1A receptors and lead to more robust disinhibition of serotonin release
  • Serotonin (5-HT) receptor partial agonism:
    • 5-HT1B partial agonism
      • Thought to have potential antidepressant effects.[1]
  • Serotonin (5-HT) receptor antagonism:
    • 5-HT3 antagonism
      • Despite vortioxetine having 5-HT3 antagonism (which is anti-nausea), there is a high incidence of nausea and vomiting.[2][3]
    • 5-HT1D antagonism
      • Thought to have impact on anxiety and vascular vasoconstriction in the brain.
    • 5-HT7 antagonism
      • Is thought give pro-cognitive effects (not clinically proven, nor approved by FDA!)
  • Vortioxetine is relatively non-toxic in overdose
  • Major depressive disorder
  • Anxiety disorders

Dosing for Vortioxetine

Starting 10 mg
Titration Increase by another 10 mg after 1 to 2 weeks, depending on tolerability
Maximum 20 mg
Taper Long-half life, self-tapering, no withdrawal side effects
  • Vortioxetine comes in an oral formulation
  • Nausea (more so than other SSRIs), vomiting, constipation; possibly less sexual SE, sedation and weight gain
  • Currently marketed by pharmaceutical companies as having more improvement on cognitive effects of depression (but this claim is very questionable).
    • This marketing strategy was based on studies showing slightly better performance on the digit substitution test, which is only a single domain test, and not a comprehensive cognitive assessment.[4]
    • The FDA in fact rejected the drug manufacturer’s request to claim that vortioxetine improved cognition in depression based on this poor quality study data.[5]
    • However, the drug company Lundbeck decided to market it saying it is “the first FDA-approved treatment for MDD to have data in the U.S. Prescribing Information showing a positive effect on processing speed.”[6]
    • Importantly, this is not the same as having FDA approval to market the drug for the actual treatment of cognitive dysfunction in depression!