Every PMHNP has their go-to medications—but what about the ones we prescribe less often? One such antidepressant for me was vortioxetine (Trintellix), a medication I used to rarely prescribe, simply because I didn’t know as much about it. Let’s change that.
What Class of Drug is Trintellix?
While Trintellix is often grouped with SSRIs, it technically falls under miscellaneous antidepressants. Some classify it more specifically as a serotonin modulator and stimulator due to its unique mechanism of action.
Vortioxetine works by inhibiting serotonin reuptake while also directly modulating various serotonin receptors, contributing to its complex pharmacology. It acts as an:
- Agonist at 5-HT1A receptors
- Partial agonist at 5-HT1B receptors
- Antagonist at 5-HT3, 5-HT7, and 5-HT1D receptors
This mixed activity may enhance antidepressant effects and reduce the risk of receptor desensitization over time.
👉 Vortioxetine: A Review of the Pharmacology and Clinical Evidence in MDD (PubMed)
FDA Approval & Name Change
Originally approved by the FDA in 2013 for the treatment of Major Depressive Disorder (MDD) in adults, vortioxetine was first marketed under the brand name Brintellix. In 2016, the name was changed to Trintellix to prevent confusion with Brilinta, an antiplatelet medication.
Though not FDA-approved for Generalized Anxiety Disorder (GAD), some providers use it off-label for that indication.
How to Start and Stop Vortioxetine
- Starting dose: 10 mg once daily
- Target dose: Up to 20 mg/day if well tolerated
- Low tolerance: Start with or reduce to 5 mg/day
It can be taken with or without food, morning or evening.
📝 Pro tip: If the medication interferes with sleep or increases restlessness, morning dosing is recommended.
Discontinuation
Vortioxetine has a long half-life (~66 hours), which means tapering may not be necessary. However, if discontinuing from 20 mg/day, some clinicians recommend tapering to 10 mg before stopping.
👉 Lexicomp Drug Monograph: Vortioxetine (subscription may be required)
Monitoring and Labs
PMHNPs should monitor:
- Depressive symptoms, anxiety, suicidal ideation
- Activation symptoms (mania, panic, akathisia)
- Signs of serotonin syndrome or hyponatremia
- Overall functioning and social engagement
Drug Interactions
Be aware of CYP enzyme interactions:
- CYP2D6 inhibitors (e.g., fluoxetine, paroxetine, bupropion): Reduce Trintellix dose by 50%
- CYP inducers (e.g., carbamazepine, phenytoin, rifampin): May require increasing dose if co-administered for 14+ days
Side Effects of Vortioxetine (Trintellix)
Most Common
- Nausea (especially at 20 mg/day)
- Constipation, dry mouth, dizziness
Other Potential Side Effects
- Abnormal dreams
- Sexual dysfunction
- Pruritus (itching)
- Diarrhea
- Headache
Serious Reactions (Though Rare)
- Activation of mania/hypomania
- Serotonin syndrome (especially when combined with other serotonergic agents)
- Bleeding risk
- Hyponatremia
Special Populations
One benefit of vortioxetine is no dose adjustment is necessary for patients with:
- Renal impairment
- Hepatic impairment
This simplifies prescribing for patients with comorbidities.
Why Consider Vortioxetine?
Vortioxetine isn’t necessarily a first-line treatment, but it may be especially helpful for patients who haven’t responded to traditional SSRIs or who have a history of SSRI withdrawal symptoms. Its unique receptor profile, mild side effect burden, and ease of discontinuation make it a worthwhile option to revisit or keep in your toolbox.
Summary for PMHNPs
As PMHNPs, it’s easy to reach for the same few medications—but part of our job is knowing how and when to explore alternatives. Vortioxetine’s novel mechanism, low discontinuation risk, and broad tolerability profile make it a useful option for managing MDD in adult patients.
Further Reading & Resources
- Rise of the “Zombie drug,” Xylazine, in the United States
- Partial Dopamine Agonists: What PMHNPs Should Know
- Latest Antipsychotic Drug Advances: Research & Developments
- Free training on diagnosing and treating mental disorders confidently and stress-free