Vortioxetine (Trintellix)

Class

Serotonin modulator and stimulator (SMS)

Mechanism

Inhibits serotonin reuptake via serotonin transporter (SERT); acts as a serotonin receptor modulator with agonist activity at 5-HT1A, partial agonist at 5-HT1B, and antagonist activity at 5-HT3, 5-HT1D, and 5-HT7 receptors, potentially enhancing serotonergic neurotransmission and cognitive function.

FDA-Approved Use

Major depressive disorder (MDD)

Off-Label Use

Generalized anxiety disorder (GAD), cognitive symptoms associated with depression, geriatric depression

Formulation

Oral tablets (5 mg, 10 mg, 15 mg, 20 mg)

Titration

5–10 mg p.o. daily, titrating up to 10–20 mg/day as clinically indicated

Dose Range

10–20 mg/day

Kinetics

Half-life ~66 hours; metabolized primarily via CYP2D6 and CYP3A4; steady state in ~2 weeks

Common AEs

Nausea, constipation, dizziness, dry mouth, sexual dysfunction

Serious/Rare AEs

Serotonin syndrome, hyponatremia

Monitoring

Monitor for serotonin syndrome and suicidality, especially in younger patients and those on other serotonergic agents

Black Box Warning

Increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults with MDD and other psychiatric disorders

Considerations

Vortioxetine tends to be well tolerated in older adults and is not associated with weight gain. Emerging research suggests it may improve cognitive function by modulating frontal cortex activity through mechanisms that differ from those of typical antidepressants/anxiolytics. Although evidence is limited in neurodegenerative conditions, vortioxetine may be a valuable treatment option for elderly patients experiencing depression with cognitive difficulties.