Prescription ·Strong evidence ·Reviewed May 2026
Vortioxetine is an oral antidepressant approved for major depressive disorder in adults. It combines serotonin reuptake inhibition with activity at several serotonin receptors, which may contribute to antidepressant effects and its distinct adverse-effect profile. It carries the class boxed warning for suicidal thoughts and behaviors in pediatric and young adult patients and must not be combined with MAO inhibitors.
The bottom line
Evidence rating strong. Most-documented uses: treatment of major depressive disorder in adults, improvement in depressed mood and anhedonia, may have relatively low rates of clinically significant weight gain compared with some older antidepressants. 3 sources indexed (2005–2026), with 4 interaction records on file.
Core mechanism
Vortioxetine inhibits the serotonin transporter and modulates serotonin signaling through receptor effects, including 5-HT3, 5-HT1D, and 5-HT7 antagonism, 5-HT1B partial agonism, and 5-HT1A agonism. These actions increase serotonergic neurotransmission and secondarily affect norepinephrine, dopamine, acetylcholine, histamine, and glutamate circuits in preclinical models. It is metabolized mainly by CYP2D6, so strong CYP2D6 inhibitors can increase exposure and require dose reduction.1,2
May be taken with or without food. Peak concentrations occur about 7 to 11 hours after dosing, and the long half-life supports once-daily dosing.3
5-HTP is a direct serotonin precursor. Combining it with vortioxetine can produce excessive serotonergic activity and serotonin syndrome.
Recommendation: Avoid 5-HTP while taking vortioxetine unless specifically directed by a specialist; seek urgent care for fever, agitation, sweating, tremor, clonus, or confusion.
Supplemental L-Tryptophan can increase serotonin synthesis and raise serotonin-toxicity risk with vortioxetine.
Recommendation: Avoid concentrated L-Tryptophan supplements during vortioxetine therapy; normal dietary protein is not the concern.
St. John's Wort has serotonergic activity and can interact unpredictably with antidepressants.
Recommendation: Do not combine St. John's Wort with vortioxetine; involve the prescriber before starting or stopping either agent.
Vortioxetine may increase bleeding tendency through serotonin effects on platelets. High-dose fish oil can have mild antiplatelet effects.
Recommendation: Use usual dietary or standard supplemental fish oil cautiously; monitor for bruising or bleeding, especially with anticoagulants, antiplatelet drugs, NSAIDs, surgery, or bleeding disorders.
Numbered references. Citations throughout the page link here.
Clinical review summarizes vortioxetine efficacy in MDD and receptor activity that differentiates it from conventional SSRIs.
Serotonergic toxicity is most often triggered by combining serotonergic agents, supporting avoidance of serotonin precursors and serotonergic herbs.
The label describes adult MDD indication, once-daily dosing, CYP2D6 dose adjustment, MAOI contraindications, and the suicidal thoughts and behaviors boxed warning.
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