Why Drug Interactions Matter with Trintellix

Trintellix (Vortioxetine) is an antidepressant that affects serotonin in the brain through multiple mechanisms. Because of how it works, combining Trintellix with certain other medications can cause serious — even life-threatening — interactions.

This guide covers the most important Trintellix drug interactions you need to know about. If you're new to the medication, start with What Is Trintellix? and How Trintellix Works for background.

Dangerous Interactions: Medications You Must Not Take with Trintellix

The following combinations are contraindicated — meaning they should never be used together:

MAOIs (Monoamine Oxidase Inhibitors)

This is the most dangerous interaction. Do not take Trintellix within 14 days of taking an MAOI, and do not start an MAOI within 21 days of stopping Trintellix. MAOIs include:

• Phenelzine (Nardil)
• Tranylcypromine (Parnate)
• Isocarboxazid (Marplan)
• Selegiline transdermal (Emsam) at doses above 6 mg/24 hours

Combining Trintellix with an MAOI can cause serotonin syndrome — a potentially fatal condition (described below).

Linezolid (Zyvox)

Linezolid is an antibiotic that also has MAOI properties. If you need Linezolid for an infection, Trintellix must be stopped first. Tell any doctor who prescribes you an antibiotic that you take Trintellix.

IV Methylene Blue

Methylene blue given intravenously (IV) has MAOI-like effects. Oral methylene blue at low doses is less of a concern, but always inform your medical team that you take Trintellix before any procedure.

Major Interactions: Medications That Require Dose Changes

Strong CYP2D6 Inhibitors

Trintellix is broken down in your liver partly by an enzyme called CYP2D6. Medications that block this enzyme can cause Trintellix to build up to higher-than-expected levels in your blood. If you take any of the following, your doctor should reduce your Trintellix dose by half:

• Bupropion (Wellbutrin)
• Fluoxetine (Prozac)
• Paroxetine (Paxil)
• Quinidine

This is especially important because Bupropion and Fluoxetine are antidepressants themselves — and some patients take them along with Trintellix. If your doctor prescribes this combination, the Trintellix dose needs to be adjusted.

Strong CYP Inducers

On the flip side, some medications speed up how fast your body breaks down Trintellix, which can make it less effective. If you take any of the following, your doctor may need to increase your Trintellix dose up to three times the original amount:

• Rifampin (an antibiotic for tuberculosis)
• Carbamazepine (Tegretol) — an anticonvulsant
• Phenytoin (Dilantin) — an anticonvulsant

When you stop the CYP inducer, your Trintellix dose should be brought back down to avoid side effects.

Serotonin Syndrome: The Most Serious Risk

Serotonin syndrome occurs when there's too much serotonin activity in the brain. It can range from mild (jitteriness, diarrhea) to severe (high fever, seizures, death). It's most likely to happen when Trintellix is combined with other serotonergic medications.

Medications That Increase Serotonin Syndrome Risk

Use the following with caution when taking Trintellix, and only under medical supervision:

• Other antidepressants: SSRIs, SNRIs, tricyclics, and MAOIs all increase serotonin. Switching between antidepressants requires careful tapering and washout periods.
• Triptans: Sumatriptan (Imitrex), Rizatriptan (Maxalt), and other migraine medications.
• Opioids: Tramadol and Fentanyl have serotonergic properties.
• Lithium: A mood stabilizer used for bipolar disorder.
• St. John's Wort: An herbal supplement commonly taken for depression. Do not take St. John's Wort with Trintellix.
• Tryptophan supplements: Sometimes taken as a sleep aid or mood booster. Avoid while on Trintellix.

Symptoms of Serotonin Syndrome

Seek immediate medical attention if you experience:

• Agitation or restlessness
• Rapid heartbeat
• High body temperature (fever)
• Muscle twitching or rigidity
• Loss of coordination
• Heavy sweating
• Severe nausea, vomiting, or diarrhea

Serotonin syndrome is a medical emergency. Call 911 or go to the emergency room immediately if you suspect it. For more on Trintellix side effects in general, see our side effects guide.

Moderate Interactions: Increased Bleeding Risk

Trintellix can affect how your blood clots. When combined with certain medications, the risk of bleeding increases:

• NSAIDs: Ibuprofen (Advil, Motrin), Naproxen (Aleve), Celecoxib (Celebrex)
• Aspirin
• Blood thinners (anticoagulants): Warfarin (Coumadin), Apixaban (Eliquis), Rivaroxaban (Xarelto)
• Antiplatelet agents: Clopidogrel (Plavix)

This doesn't mean you can never take ibuprofen while on Trintellix, but you should be aware of the increased risk. Tell your doctor if you take any of these regularly. Watch for signs of bleeding such as unusual bruising, nosebleeds, or blood in your stool.

Food and Supplement Interactions

The good news: Trintellix has no significant food interactions. You can take it with or without food, and there are no foods you need to avoid.

However, watch out for these supplements:

• St. John's Wort: Increases serotonin syndrome risk. Do not take with Trintellix.
• Tryptophan (5-HTP): Also increases serotonin. Avoid while taking Trintellix.

Alcohol is not a direct drug interaction, but it's generally recommended to limit alcohol while taking any antidepressant. Alcohol can worsen depression symptoms and may increase the risk of side effects like dizziness.

What to Tell Your Doctor Before Starting Trintellix

Before your doctor prescribes Trintellix, make sure they know about:

1. Every medication you take — prescription and over-the-counter
2. All supplements and herbal products — especially St. John's Wort and tryptophan
3. Any recent medication changes — particularly if you've recently stopped an MAOI or another antidepressant
4. Your pharmacy — so they can run an electronic drug interaction check
5. Any genetic test results — CYP2D6 poor metabolizers should not exceed 10 mg/day

If you're looking for a prescriber, our guide on finding a doctor who prescribes Trintellix can help.

What to Tell Other Doctors and Pharmacists

If you're seeing multiple healthcare providers, always tell them you're taking Trintellix. This is especially important:

• Before any surgery (anesthesia teams need to know)
• At urgent care or the ER
• When starting any new medication — even something that seems unrelated
• At the pharmacy — pharmacists can catch interactions your doctor might miss

The Bottom Line

Trintellix is generally safe when taken as prescribed, but it has several important drug interactions that both patients and doctors need to be aware of. The most critical rule: never combine Trintellix with MAOIs. Beyond that, be cautious with other serotonergic drugs, CYP2D6 inhibitors, and blood thinners.

Always keep an updated medication list and share it with every healthcare provider you see. When in doubt, ask your pharmacist — they're experts at spotting interactions.

Need help finding Trintellix or saving money on it? Visit MedFinder or check our savings guide.