What is the classification of Trintellix (vortioxetine)?

Trintellix (Vortioxetine) Classification

Trintellix (vortioxetine) is classified as a multimodal antidepressant with serotonin modulator and stimulator (SMS) activity, distinct from traditional selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). 1

Primary Drug Classification

• Vortioxetine is officially designated as an antidepressant with multimodal activity targeting multiple serotonin receptors and the serotonin transporter simultaneously 1, 2

• The FDA describes vortioxetine as having a mechanism that "is thought to be related to its enhancement of serotonergic activity in the CNS through inhibition of the reuptake of serotonin (5-HT)" but emphasizes that it "also has several other activities including 5-HT3 receptor antagonism and 5-HT1A receptor agonism" 1

Specific Pharmacological Profile

• Vortioxetine binds with high affinity to the serotonin transporter (Ki=1.6 nM) and potently inhibits serotonin reuptake (IC50=5.4 nM), but does NOT significantly bind to norepinephrine (Ki=113 nM) or dopamine (Ki>1000 nM) transporters 1

• The drug simultaneously acts on five different serotonin receptor subtypes: 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) 1, 2

• Functionally, vortioxetine serves as:

  • A serotonin transporter (SERT) blocker 2
  • A 5-HT3, 5-HT7, and 5-HT1D receptor antagonist 1, 2
  • A 5-HT1A receptor agonist 1, 2
  • A 5-HT1B receptor partial agonist 1

Why It's NOT Simply an SSRI

• Vortioxetine is "more than just a SSRI" due to its supplementary capacity of acting directly on several subtypes of serotonin receptors, which distinguishes it from traditional SSRIs that primarily block serotonin reuptake 3

• The American College of Physicians recognizes vilazodone as the medication most similar to vortioxetine because it also combines SSRI action with 5-HT1A receptor partial agonism, though vortioxetine has broader receptor activity 4

Clinical Context

• Vortioxetine is approved for treatment of major depressive disorder (MDD) in adults at doses ranging from 5-20 mg once daily 1, 2

• The multimodal mechanism contributes to unique procognitive effects not typically seen with traditional SSRIs or SNRIs, making it particularly valuable for patients with cognitive symptoms of depression 3, 5

• Serotonin transporter occupancy in humans is approximately 50% at 5 mg/day, 65% at 10 mg/day, and 80% at 20 mg/day 1