Skip to main content
Drug Info

Trintellix side effects, interactions, and how to avoid them

Learn about potential side effects of Trintellix, drug interactions, and more to see if it's right for you
SingleCare logo
By | Updated on Jan. 15, 2025 Medically reviewed by Gerardo Sison, Pharm.D.
Rx pad and bottle: What are the Trintellix side effects?

Key takeaways

  • Trintellix treats major depressive disorder by balancing serotonin, as well as improving mood and cognition. 

  • Common side effects like nausea, dizziness, or dry mouth are typically mild and may subside over time.

  • Trintellix has minimal effects on weight but may negatively affect sexual function like other antidepressants.

  • Serious risks include serotonin syndrome, suicidal thoughts, withdrawal symptoms, and low sodium levels.

In this article:

Trintellix is a brand-name prescription drug that treats major depressive disorder (MDD). Vortioxetine, the active ingredient in Trintellix, is believed to balance serotonin levels in the brain, which may help improve mood, memory, and cognitive function in those with depression. Trintellix is an effective medication, but it may not be the right medication for everyone because of possible side effects.

RELATED: How long does Trintellix take to work?

Common side effects of Trintellix

Most side effects occur just after starting the medication. However, the side effects of Trintellix are generally mild and go away as the body adjusts to the medication. Some side effects may stick around for as long as the treatment continues. The most common side effects of Trintellix are:

  • Nausea
  • Vomiting 
  • Constipation
  • Diarrhea
  • Dry mouth
  • Dizziness
  • Gas
  • Abnormal dreams
  • Itching
  • Sexual dysfunction

RELATED: Does Trintellix cause sexual side effects?

Unlike other antidepressants, drowsiness is not known to be a common side effect of vortioxetine. Studies suggest vortioxetine may improve sleep cycles and help reduce daytime drowsiness.

Trintellix weight changes

Many antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), are known to be associated with weight gain. Trintellix, on the other hand, appears to have minimal effects on body weight. 

In clinical studies that followed patients over six months, Trintellix had no significant effects on body weight. However, one study showed patients gained an average of around one pound while on Trintellix after 52 weeks or one year of treatment. About 18% of study participants taking Trintellix gained or lost 7% of their original weight at the beginning of the study. Trintellix, then, has less of an effect on weight than other antidepressants, but weight changes are possible and will vary by person.

Trintellix withdrawal

Like other medications that affect serotonin in the brain, Trintellix should not be discontinued abruptly. Although the drug is not addictive, the dosage should be gradually decreased over several weeks before stopping to prevent discontinuation syndrome or withdrawal symptoms. The most common Trintellix withdrawal symptoms include:

  • Nausea
  • Sweating
  • Agitation
  • Irritability
  • Dizziness
  • Anxiety
  • Confusion
  • Insomnia
  • Headache

Discontinuation syndrome may take a few hours to five days to appear and may persist for up to 10 days or more. Usually, these symptoms resolve without treatment.

Serious side effects of Trintellix

Trintellix can cause serious side effects, including:

  • Suicidal thoughts and behaviors
  • Serotonin syndrome
  • Bleeding problems
  • Worsened manic episodes in people with bipolar disorder
  • Angle-closure glaucoma
  • Low sodium levels
  • Severe allergic reactions, including anaphylaxis or angioedema

Suicidal thoughts and behaviors

Trintellix carries a boxed warning from the U.S. Food and Drug Administration (FDA) about an increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults. When taking Trintellix, individuals who may be at risk should be closely monitored for signs of suicidality, such as:

  • Thoughts or comments about suicide
  • Attempts to commit suicide
  • Unusual mood changes
  • Severe anger, irritability, or aggression
  • Agitation or restlessness
  • New or worsening depression
  • New or worsening anxiety
  • Panic attacks 
  • Risk-taking behaviors or dangerous impulses

Serotonin syndrome

Antidepressants like vortioxetine may cause serotonin syndrome, a potentially serious condition caused by too much serotonin in the brain. Discontinue Trintellix immediately and seek immediate medical care if you notice signs of serotonin syndrome such as:

  • Agitation 
  • Hallucinations
  • Loss of coordination
  • Muscle twitching
  • Rigid muscles
  • Rapid heartbeat
  • High or low blood pressure
  • Sweating 
  • Fever
  • Nausea or vomiting
  • Confusion
  • Mood changes
  • Diarrhea
  • Seizures

Low blood sodium

Serotonergic drugs like vortioxetine may cause SIADH, a problem with the hormone that controls the body’s elimination of water and electrolytes from the body. SIADH, in turn, could cause the levels of salt (sodium) in the blood to fall, a condition called hyponatremia. Low blood sodium can be a serious medical condition with symptoms such as:

  • Confusion
  • Memory loss
  • Headache
  • Nausea
  • Difficulty concentrating
  • Unsteadiness
  • Hallucinations
  • Fainting
  • Seizures 
  • Coma

Angle-closure glaucoma

Angle-closure glaucoma is an eye problem that can happen suddenly and cause vision loss or blindness in just a few hours or days. It happens when the drainage system for the eye located between the iris and the cornea is blocked, causing fluid to quickly accumulate within the eye. Watch for symptoms such as:

  • Eye pain
  • Vision changes
  • Red or swollen eyes 
  • Headache
  • Nausea or vomiting

People with “narrow angles” between the iris and the cornea are most at risk for developing angle-closure glaucoma. Narrow angles can be diagnosed during a routine eye exam and are typically treatable through surgery.

How long do Trintellix side effects last?

Mild side effects are temporary and will usually subside as treatment continues. Other side effects may disappear within a few days after the medication is discontinued. 

Severe side effects usually take longer to resolve. Mild cases of serotonin syndrome typically resolve within one to three days of discontinuing the medication, but severe cases require immediate medical attention. In symptomatic cases of low blood sodium, Trintellix should be discontinued, and a healthcare provider should be contacted. Severe cases of low blood sodium levels may require hospitalization.

Trintellix contraindications & warnings

Trintellix may not be the right medication for everyone. For various reasons, some people may not be able to take the medication, while others may need to be cautious while using it.

Allergies

Anyone with severe allergies to Trintellix should not take the medication. Experiencing a serious allergic reaction is a medical emergency. Seek medical help if you experience hives, trouble breathing, or swelling of the face or throat after taking Trintellix. 

Monoamine oxidase inhibitors

You should not use Trintellix if you are currently taking monoamine oxidase inhibitors (MAOIs) or have taken them recently. You must wait at least 14 days after stopping an MAOI before starting Trintellix. In addition, if you are currently on Trintellix, you should not take an MAOI for at least 21 days after stopping Trintellix. Also, do not start Trintellix if you are being treated with linezolid or intravenous methylene blue. 

Poor metabolizers

Some people don’t break down vortioxetine very well. In poor metabolizers, the drug can linger at high concentrations, increasing the risk of side effects. Fortunately, people can be genetically tested. Poor metabolizers will be restricted to a maximum daily dose of 10 mg.

Children

Trintellix is FDA-approved for use in adults 18 and older. Trintellix has not been determined to be either safe or effective for children.

Seniors

Trintellix has been shown to be effective and safe in people older than 65. No dose adjustment is required.

Pregnancy and breastfeeding

There isn’t enough research to fully understand if Trintellix is safe during pregnancy. If you are pregnant or thinking about becoming pregnant, it’s important to talk to a healthcare provider before starting or stopping this medication. Using Trintellix in the third trimester could increase the chances of serious lung problems and withdrawal symptoms for newborns. 

Likewise, there is not enough research or information on whether Trintellix passes into breast milk or affects a nursing baby. The Drugs and Lactation Database (National Library of Medicine) advises mothers who are taking Trintellix to switch to alternative medications before breastfeeding an infant. The other alternative is to find a different way to feed the infant.

Trintellix interactions

Trintellix has several drug interactions that can lead to various adverse effects. It’s important to discuss any medications you take with a healthcare provider, including prescription medicines, over-the-counter drugs, and dietary supplements, before starting Trintellix. 

Trintellix and MAOIs

Trintellix should not be taken with MAOIs due to an increased risk of serotonin syndrome. These drugs include:

Trintellix and serotonergic drugs

Medications that increase serotonin levels are called serotonergic drugs. Some of these medications can greatly affect serotonin levels, while others do not. The risk of serotonin syndrome increases when two or more serotonergic drugs are taken together. For this reason, combining other serotonergic drugs with Trintellix is to be avoided. Serotonergic drugs include:

  • Antidepressants such as: 
    • Tricyclic antidepressants, Elavil (amitriptyline), Tofranil (imipramine), and Anafranil (clomipramine)
    • SSRIs (selective serotonin reuptake inhibitors) such as Celexa (citalopram), Paxil (paroxetine), Zoloft (sertraline), and Prozac (fluoxetine) 
    • SNRIs (selective serotonin and norepinephrine reuptake inhibitors) such as Cymbalta (duloxetine) and Effexor (venlafaxine)
    • Wellbutrin (bupropion)
  • Stimulants such as Adderall (amphetamine/dextroamphetamine), Ritalin (methylphenidate), and Concerta (methylphenidate)
  • Drugs that treat or prevent nausea, such as Zofran (ondansetron) and Anzemet (dolasetron)
  • Cough medicines containing dextromethorphan
  • Migraine medications, including triptans and ergot drugs
  • Opioids such as Ultram (tramadol) and Fentora (fentanyl)
  • Antipsychotics such as Clozaril (clozapine), Seroquel (quetiapine), and Risperdal (risperidone)
  • Anticonvulsants such as Tegretol (carbamazepine) and Neurontin (gabapentin)
  • Herbal supplements such as St. John’s wort, tryptophan, and Yohimbe

This might not be a complete list of drugs that can interact with Trintellix. Always consult a healthcare provider before taking Trintellix if you have other medications in your treatment plan. 

Trintellix and blood thinners (anticoagulants)

Trintellix may increase the risk of bleeding problems. Therefore, treatment must be monitored if a person takes blood thinners such as Coumadin (warfarin) or Plavix (clopidogrel). Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen also interfere with blood clotting, so they may need to be used sparingly when taking Trintellix. In addition, some anticancer drugs and steroids may also increase the risk of bleeding episodes when taken with Trintellix.

Many people are unaware that some popular dietary and herbal supplements interfere with blood clotting. The following herbal supplements may need to be used with caution or avoided when taking Trintellix:

  • Garlic
  • Ginkgo biloba
  • Krill oil
  • Saw palmetto
  • Willow bark 

Trintellix and diuretics

Trintellix increases the risk of low sodium levels in the blood. Diuretics (water pills) could contribute to the problem by increasing sodium excretion. Therefore, treatment with diuretics may need to be monitored or modified. 

Drugs that decrease the effectiveness of Trintellix

Some drugs speed up the body’s metabolism of vortioxetine, reducing its effectiveness. These include:

  • The antibiotics rifampin, rifapentine, rifamycin, rifaximin, and rifabutin
  • Certain anticonvulsant drugs, such as carbamazepine and phenytoin
  • Some types of antiviral drugs
  • Barbiturates such as butalbital and butabarbital

When taking these drugs, the Trintellix dose may need to be increased.

Drugs that increase the side effects of Trintellix

Some drugs slow down the body’s metabolism of vortioxetine, increasing the risk and severity of possible side effects. These include:

  • Some antidepressants like Wellbutrin (bupropion), Paxil (paroxetine), and Prozac (fluoxetine)
  • Certain drugs that treat an irregular heart rate, such as Cardioquin (quinidine)

When taken with these medications, a healthcare provider may need to decrease the Trintellix dose by as much as half.

Trintellix and alcohol

There is no evidence drinking alcohol will cause additional impairment while taking vortioxetine. However, it’s generally recommended that individuals avoid drinking alcohol while taking antidepressants like Trintellix.

How to avoid Trintellix side effects

Not everyone taking Trintellix will experience side effects. For those that do, side effects will often be minimal. There are, however, a few ways to potentially reduce the risk of side effects:

1. Take Trintellix as directed

Take the dose prescribed, usually 5 to 20 mg once daily. Do not take extra medicine, cut the dose, or skip a day or two. Trintellix can be taken with a meal or on an empty stomach. 

2. Do not stop taking Trintellix suddenly

Avoid stopping Trintellix all at once. There may be side effects. If the medicine does not seem to work or side effects are hard to manage, talk to your prescribing physician, pharmacist, or other healthcare professional about changing the dose or switching to a new medication. If it is agreed the medication should be discontinued, the best way is to steadily taper or lower the dose according to your healthcare provider’s instructions.

3. Do not miss doses

Not taking antidepressants as prescribed can make them less effective. If you miss too many doses in a row, the symptoms you’re trying to treat might come back. To help remember to take your next dose, try keeping a diary of your doses, using an app on your phone, organizing your pills in a seven-day container, or setting an alarm for each day’s dose.

4. Tell your healthcare provider about all medical conditions

Sharing a full medical history can help prevent side effects. Before starting Trintellix, tell your healthcare provider about physical or mental health conditions. You should especially discuss whether you have a history of the following:

  • Bipolar disorder
  • Bleeding problems
  • Eye problems
  • Low sodium levels

You should also make sure you tell the doctor about pregnancy, nursing, or any plans to become pregnant or nurse a baby.

5. Tell your healthcare provider about all medications being taken

Trintellix has several adverse effects due to drug interactions. Tell your healthcare provider about all medications and supplements you take, including:

  • Medicines that treat mood, anxiety, psychosis, or other psychiatric disorders 
  • MAO inhibitors
  • Blood thinners
  • Diuretics
  • Migraine medications
  • Pain medications such as opioids or NSAIDs
  • Anticonvulsants
  • All over-the-counter medications, supplements, and herbal remedies you take, especially St. John’s wort and tryptophan.

If you are unsure about a drug, a physician, pharmacist, or other healthcare provider can help you identify it. If you are taking two or more prescription medications, keep a list of all these medications on hand. Be ready to consult that list when discussing your treatment plan with a healthcare professional.