What not to mix with Trintellix? A Guide to Dangerous Drug Interactions

October 10, 2025 •

3 min read

According to the U.S. Food and Drug Administration (FDA), combining Trintellix with certain medications, including monoamine oxidase inhibitors (MAOIs), can cause a potentially life-threatening condition called serotonin syndrome. Understanding what not to mix with Trintellix is crucial for patient safety.

Quick Summary

This article outlines the medications, supplements, and substances that interact negatively with Trintellix (vortioxetine), increasing the risk of serious side effects like serotonin syndrome and abnormal bleeding.

Key Points

MAOIs: Never take Trintellix with MAOIs or within a 14 to 21-day washout period due to the high risk of fatal serotonin syndrome.
Serotonergic Drugs: Avoid combining Trintellix with other medications and supplements that increase serotonin, like other antidepressants, triptans, and St. John's wort, to prevent serotonin syndrome.
Bleeding Risk: Use caution when mixing Trintellix with blood thinners (anticoagulants), antiplatelets, and NSAIDs, as it significantly increases the risk of abnormal bleeding.
Metabolism Effects: Be aware that CYP2D6 inhibitors (like bupropion) can increase Trintellix levels, while CYP2D6 inducers (like carbamazepine) can decrease them, impacting its efficacy.
Alcohol: Avoid or limit alcohol use, as it can worsen depression and intensify common side effects like dizziness and nausea.
Consultation is Key: Always inform your healthcare provider about all medications, supplements, and substances you are taking before starting or changing Trintellix dosage.

Serotonin Syndrome: A Major Risk with Combination Therapy

Trintellix (vortioxetine) works by increasing serotonin levels in the brain to help treat depression. Combining Trintellix with other substances that also increase serotonin significantly raises the risk of serotonin syndrome, a potentially dangerous condition. Symptoms can range from mild, such as agitation and rapid heart rate, to severe and life-threatening.

MAOIs (Monoamine Oxidase Inhibitors)

The most critical interaction to avoid is the combination of Trintellix with MAOIs. These antidepressants prevent serotonin breakdown, and taking them with Trintellix can lead to dangerously high serotonin levels. A washout period is essential when switching between these medications.

Washout period: Wait at least 14 days after stopping an MAOI before starting Trintellix, and at least 21 days after stopping Trintellix before starting an MAOI.
Examples of MAOIs: Include Phenelzine (Nardil), Isocarboxazid (Marplan), Tranylcypromine (Parnate), and Selegiline (Emsam). The antibiotic Linezolid and intravenous Methylene Blue are also considered MAOIs.

Other Serotonergic Agents

Other medications and supplements can also increase serotonin levels and the risk of serotonin syndrome when combined with Trintellix. These include other antidepressants (SSRIs, SNRIs, TCAs), certain pain medications like tramadol and fentanyl, triptans for migraines, lithium, buspirone, and amphetamines. The herbal supplement St. John's wort should also be avoided.

Increased Risk of Bleeding

Combining Trintellix with medications that thin the blood increases the risk of abnormal bleeding. Trintellix can affect platelets, and this interaction can lead to bruising, nosebleeds, or more serious gastrointestinal bleeding.

Comparison of Common Bleeding-Risk Medications with Trintellix


Drug Type	Drug Examples	Resulting Interaction	Level of Risk with Trintellix
Anticoagulants	Warfarin (Coumadin), Apixaban (Eliquis)	Greatly increased risk of serious bleeding events	High
Antiplatelets	Aspirin, Clopidogrel (Plavix)	Increased risk of bruising and bleeding	High
NSAIDs	Ibuprofen (Advil), Naproxen (Aleve)	Increased risk of bleeding, especially gastrointestinal	High

Medications Affecting Trintellix Effectiveness

Some medications can influence the liver enzymes that process Trintellix, altering its concentration in the body.

CYP2D6 Inhibitors

These drugs slow down the enzyme CYP2D6, potentially increasing Trintellix levels and side effects. A dose adjustment of Trintellix may be needed. Examples include bupropion, fluoxetine, paroxetine, and quinidine.

CYP2D6 Inducers

These medications speed up the CYP2D6 enzyme, which can decrease Trintellix levels and reduce its effectiveness. Examples are rifampin, carbamazepine, and phenytoin.

The Combination of Trintellix and Alcohol

It is generally recommended to avoid or limit alcohol while taking Trintellix. Alcohol is a depressant and can worsen depression symptoms, potentially counteracting Trintellix's benefits. It can also intensify side effects like dizziness and nausea. For those also on blood thinners, alcohol further increases bleeding risk.

Conclusion: Always Consult Your Healthcare Provider

Given the potential for serious interactions with MAOIs, other serotonergic agents, blood thinners, and medications affecting its metabolism, discussing all substances you are taking with your healthcare provider is crucial before starting or adjusting Trintellix. This includes all prescription and over-the-counter drugs, herbal supplements like St. John's wort, and alcohol consumption. Never stop Trintellix abruptly without medical guidance due to the risk of discontinuation syndrome. Your doctor can refer to resources like the FDA Prescribing Information for comprehensive details.

Frequently Asked Questions

It is best to avoid or limit alcohol while taking Trintellix. While there is no direct interaction, alcohol can worsen depression symptoms and may increase common side effects like dizziness and nausea.

Serotonin syndrome is a potentially life-threatening condition caused by an excess of serotonin. Symptoms can include agitation, hallucinations, rapid heart rate, high blood pressure, sweating, fever, muscle twitching, loss of coordination, nausea, and vomiting.

Combining NSAIDs with Trintellix can increase the risk of bleeding, particularly gastrointestinal bleeding. You should consult your doctor before using them together.

Taking Trintellix with a monoamine oxidase inhibitor (MAOI) is strictly prohibited due to the high risk of a potentially fatal case of serotonin syndrome. A significant washout period is required between stopping one and starting the other.

Yes, Trintellix interacts with St. John's wort. This herbal supplement increases serotonin levels, and combining it with Trintellix can significantly increase the risk of serotonin syndrome.

Trintellix can increase the risk of serotonin syndrome when taken with other antidepressants, including SSRIs (e.g., Prozac) and SNRIs (e.g., Cymbalta). Combination therapy must be carefully managed by a healthcare provider.

It is crucial to inform your doctor about all supplements, especially those that can affect serotonin levels or blood clotting. If you realize you forgot to mention something, contact your doctor immediately.