Vortioxetine
Trintellix
Serotonin Modulator and StimulatorGeneric availableTDM data
The mechanism of the antidepressant effect of vortioxetine is not fully understood, but is thought to be related to its enhancement of serotonergic activity in the CNS 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 vortioxetine's antidepressant effect has not been established.
Compare Vortioxetine →FDA-Approved Indications
- Major depressive disorder (adults)
Common Off-Label Uses
- Generalized anxiety disorder
- Cognitive dysfunction in MDD
What Sets This Drug Apart
- Multimodal serotonergic mechanism: combines SERT inhibition with 5-HT1A agonism and 5-HT3/5-HT7 antagonism — pharmacologically distinct from SSRIs
- Cognitive benefits noted in trials: improved verbal learning, processing speed, and executive function vs placebo — distinguishing clinical claim among antidepressants
- Very long half-life (~66 hours); takes 2+ weeks to reach steady state; effects of dose changes are slow to manifest
- Dose-dependent nausea is the signature tolerability issue (8% at 5 mg, up to 30% at 20 mg); starting at 10 mg with food minimizes this
- CYP2D6 substrate — halve max dose to 10 mg in CYP2D6 poor metabolizers; no dose adjustment needed for hepatic or renal impairment
- FDA-approved for MDD only; no anxiety disorder indications despite serotonergic mechanism
Boxed Warning
SUICIDAL THOUGHTS AND BEHAVIORS