From Bupropion and Tramadol to Warfarin: 5 Trintellix Interactions to Watch For

Trintellix (vortioxetine) is an atypical antidepressant prescribed to treat depression in adults. Trintellix is safe to take in most cases, but certain medications can interact negatively with it.

Some Trintellix drug interactions happen because of how your body breaks the medication down. For instance, after taking Trintellix, certain enzymes (proteins) in your liver are in charge of processing the dose and clearing it out of your system. Other medications, though, can speed up or block these proteins, which can affect the amount of Trintellix in your body.

Other interactions occur due to the way Trintellix works, boosting serotonin levels in your body. If you also take other medications that boost serotonin, it can raise the risk of side effects.

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Some medications that interact with Trintellix are available by prescription, while others are available over the counter (OTC). Here, we’ll dive deeper into five types of Trintellix drug interactions to keep in mind while you’re taking this oral tablet.

1. Medications that increase Trintellix levels

After you take a dose of Trintellix, an enzyme (protein) in your liver called CYP2D6 is responsible for breaking down the medication and clearing it from your body.

Some medications, called enzyme inhibitors, can block this enzyme. This means it won’t work as well as it should. Taking a CYP2D6 enzyme inhibitor with Trintellix can cause levels of Trintellix to build up in your body. This may result in unwanted and sometimes serious side effects.

Examples of medications that inhibit this enzyme include:

• Bupropion (Wellbutrin SR, Wellbutrin XL, Forfivo XL)

• Fluoxetine (Prozac)

• Paroxetine (Paxil)

• Quinidine

If you need to take one of these enzyme inhibitors with Trintellix, your prescriber may decrease your Trintellix dose. This helps prevent Trintellix from building up in your body. But if you stop taking the enzyme inhibitor, your prescriber will likely increase your Trintellix dose back to the regular dosage.

EXPERT PICKS: WHAT TO READ NEXT

• What’s the best Trintellix dosage? This pharmacist-backed dosage guide details typical Trintellix dosages for adults and when a dose adjustment might be necessary.

• Can you take St. John’s wort with Trintellix? St. John’s wort is a supplement that some people take to help manage depression symptoms, but it’s notorious for causing interactions. Check out how it interacts with Trintellix.

• SSRI interactions: Learn about potential drug interactions with selective serotonin reuptake inhibitors, a common group of antidepressants.

Before starting Trintellix, it’s a good idea to talk with your prescriber about all the medications and supplements you take. It’s also a good idea to let them know if you start or stop taking a medication at any point.

2. Medications that decrease Trintellix levels

Just as some medications block CYP2D6 enzymes, others can do the opposite. They can make the protein overactive. These medications are called enzyme inducers.

Taking an enzyme inducer with Trintellix may cause the medication to break down too quickly. In this case, Trintellix may not work as well. Examples of CYP2D6 enzyme inducers include:

• Rifampin (Rimactane)

• Carbamazepine (Tegretol, Equetro, others)

• Phenytoin (Dilantin, Phenytek)

If you need to take an enzyme inducer for longer than 2 weeks, your prescriber will likely increase your Trintellix dose. They’ll adjust your dosage until Trintellix starts to work well for your symptoms. However, your new dosage should not be higher than three times the regular dose.

Let your prescriber know right away if you stop taking the enzyme inducer. They’ll need to lower your Trintellix dosage within 14 days of stopping the other medication. Doing so reduces the likelihood of having unwanted side effects from Trintellix.

3. Medications that increase serotonin

Trintellix works by increasing serotonin in your brain and body. Serotonin is a chemical that helps regulate mood, memory, and other functions.

Having the right balance of serotonin can help treat health conditions such as depression. However, too much could result in complications, including serotonin syndrome. Serotonin syndrome is a rare condition in which your serotonin levels rise to dangerous levels. Taking more than one medication that raises serotonin increases the risk of developing serotonin syndrome.

Examples of medications that increase serotonin include:

• Other antidepressants, such as fluoxetine

• Anti-anxiety medications, such as buspirone 

• Some pain medications, such as tramadol (ConZip)

• Triptan migraine treatments, such as sumatriptan (Imitrex)

• Amphetamines, such as Adderall (amphetamine salts)

• Mood stabilizers, such as lithium (Lithobid)

• Certain supplements, such as St. John’s wort

Symptoms of serotonin syndrome can range from mild to severe. In rare cases, they may even become life-threatening. Mild symptoms can include nausea, dizziness, and rapid heart rate. More severe symptoms include seizures and coma.

Let your healthcare team know right away if you think you’re experiencing serotonin syndrome. They’ll likely have you stop taking Trintellix and any other serotonin-boosting medications. If your symptoms seem severe, go to the ER right away.

4. Monoamine oxidase inhibitors

Monoamine oxidase inhibitors (MAOIs) are an older group of medications. They typically treat depression, but some MAOIs treat other conditions, such as Parkinson’s disease or infections (i.e., pneumonia).

Examples of MAOIs include:

• Phenelzine

• Isocarboxazid (Marplan)

• Tranylcypromine

• Selegiline (Emsam, Zelapar)

• Linezolid (Zyvox)

• Methylene blue (ProvayBlue)

Like Trintellix, MAOIs increase serotonin levels in your body. And taking an MAOI with Trintellix increases the risk of serotonin syndrome.

It’s not recommended to take Trintellix while you’re taking an MAOI. In fact, if you’re about to start Trintellix after taking an MAOI, your prescriber will have you wait at least 14 days after stopping the MAOI. If you need to start an MAOI after taking Trintellix, you’ll need to wait at least 21 days after stopping Trintellix.

5. Medications that increase bleeding risk

Trintellix may increase your risk of bleeding. This can happen because serotonin plays a role in activating platelets (blood clotting cells).

Try not to take Trintellix with other medications that also increase the risk of bleeding. Doing so worsens the likelihood of easy bleeding or bruising overall. Examples include:

• Anticoagulants, such as warfarin (Coumadin, Jantoven) and apixaban (Eliquis)

• Antiplatelets, such as clopidogrel (Plavix)

• Nonsteroidal anti-inflammatory drugs, such as ibuprofen (Advil, Motrin), naproxen (Naprosyn, Aleve), and aspirin

This isn’t a full list of medications that can increase bleeding. Be sure to provide your prescriber with a full list of your medications before you begin Trintellix (or if you start a new medication while taking Trintellix).

What’s more, contact a healthcare professional right away if you have signs or symptoms of unusual bleeding. These can include reddish brown spotting on your skin, nosebleeds, or blood in your urine. If you experience bleeding that doesn’t stop, extreme weakness, or large amounts of blood in your urine or stool, call 911 or go to the nearest ER right away.

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Written by:

Rosanna Sutherby, PharmD

Rosanna Sutherby, PharmD, has been a community pharmacist in North Carolina for over 23 years. Before beginning her work as a medical writer, she held positions as a pharmacy manager, staff pharmacist, and immunizer.

Edited by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

Reviewed by:

Renad Abu-Sawwa, PharmD, BCPPS

Renad Abu-Sawwa, PharmD, BCPPS, is an associate professor and associate discipline director of clinical pharmacology at Rush Medical College with a practice site as a clinical pharmacy specialist practitioner at RUSH Children's Hospital in the Pediatric Epilepsy Clinic.

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