BLACK BOX WARNING
- suicidality in children, adolescents, and young adults
vortioxetine
Brand: Trintellix
⚠ BBW Prototype Drug
Drug Class: multimodal antidepressant
Drug Family: antidepressant
Subclass: serotonin modulator and stimulator
Organ Systems: cns
Mechanism of Action
Combines SERT inhibition with direct modulation of multiple serotonin receptor subtypes: agonism at 5-HT1A (autoreceptors, anxiolytic), partial agonism at 5-HT1B, and antagonism at 5-HT3 and 5-HT7 (reduces nausea and may enhance cognitive function). This multimodal activity distinguishes it from conventional SSRIs.
SERT (serotonin transporter)5-HT1A receptor (agonist)5-HT1B receptor (partial agonist)5-HT3 receptor (antagonist)5-HT7 receptor (antagonist)
Indications
- major depressive disorder
Contraindications
- concurrent MAOI use
Adverse Effects
Common
- nausea
- diarrhea
- dry mouth
- dizziness
- constipation
Serious
- serotonin syndrome
- suicidal ideation
- abnormal bleeding
- hyponatremia
Pharmacokinetics (ADME)
| Absorption | well absorbed orally; bioavailability ~75%; not significantly affected by food |
| Distribution | protein binding ~98%; Vd ~2600 L |
| Metabolism | primarily via CYP2D6 (major) with minor contributions from CYP3A4, 2A6, 2B6, 2C8, 2C9, 2C19 |
| Excretion | renal (~59%) and fecal (~26%); primarily as inactive metabolites |
| Half-life | 66 hours |
| Onset | 2-4 weeks for full antidepressant effect |
| Peak | 7-11 hours |
| Duration | 24 hours |
| Protein Binding | 98% |
| Vd | 2600 L |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| MAOIs | serotonin syndrome | contraindicated |
| CYP2D6 inhibitors (bupropion, paroxetine) | increases vortioxetine exposure; reduce dose by half | major |
| CYP inducers (rifampin) | decreases vortioxetine levels; increase dose up to 3x | moderate |
Nursing Considerations
- Nausea is the most common adverse effect and is dose-dependent; starting at 5 mg and titrating up over 2-4 weeks can reduce nausea during initiation.
- CYP2D6 inhibitors (bupropion, paroxetine, fluoxetine) significantly increase vortioxetine levels — review combination therapy and consider dose reduction to 10 mg/day.
- Vortioxetine has been studied for cognitive function in depression, showing improvements in processing speed and executive function; this may be a differentiating factor for patients with prominent cognitive symptoms.
- Unlike SSRIs, sexual dysfunction appears to be lower with vortioxetine (rates similar to placebo in trials); this may be a consideration for patients with prior SSRI-induced sexual side effects.
Clinical Pearls
- Vortioxetine's clinical differentiation from SSRIs is its potential pro-cognitive effect; it is one of the few antidepressants with RCT data showing improvement in cognitive domains (memory, attention, processing speed) beyond mood symptoms.
- Its 66-hour half-life allows for some flexibility in missed doses without the precipitous withdrawal symptoms seen with short-half-life drugs like paroxetine.
Safety Profile
Pregnancy use-with-caution
Lactation use-with-caution
Renal Adjustment Not required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.