Canada Pharmacy Depot

Safety and Side Effects of Trintellix

Tuesday 19 March 2024
7 minute(s) read

Table of Contents

I. Trintellix Side Effects

II. Trintellix Drug Interactions

III. Trintellix Usage During Pregnancy

IV. Conclusion

Trintellix is an FDA-approved medication used to treat major depressive disorder (MDD) in adults. It works by balancing certain chemicals in the brain that affect your mood. [1]

One of the remarkable aspects of Trintellix is its ability to start improving depressive symptoms within two weeks of starting treatment. While the full effects of the medication typically manifest around four weeks or later, the initial signs of progress can provide much-needed relief. [2]

Trintellix falls into a category of antidepressants called atypical antidepressants. These medications are often prescribed when other antidepressants have not been effective. However, Trintellix may also be used as an initial treatment for depression, depending on a person's symptoms and medical history. [3]

While Trintellix can be a valuable tool in managing depression, it's crucial to prioritize safety when taking any medication. In this article, we will explore the potential side effects of Trintellix, its interactions with other drugs, and other important safety information.

Trintellix Side Effects

When starting a new medication like Trintellix, it's normal to experience some side effects. Many of these side effects are mild and will likely disappear over time. However, some side effects can be more serious. Being aware of the range of possible side effects can help you know what to expect and when to contact your doctor.

Common Side Effects

As with any medication, Trintellix may cause side effects while your body adjusts to the drug. These side effects are often temporary, lasting only a few days or weeks. If any side effects continue for longer than that or become severe, consult your doctor right away. [4]

Common side effects may include:

  • Constipation
  • Diarrhea
  • Dry mouth
  • Nausea
  • Vomiting
  • Dizziness
  • Nausea
  • Itching
  • Mild allergic reaction [4]

Serotonin Syndrome

Trintellix works by increasing levels of the neurotransmitter serotonin in your brain. While this effect can help improve your mood and symptoms of depression, it also means there is a risk of developing a condition called serotonin syndrome. This potentially dangerous reaction can happen when you have too much serotonin buildup in your body. [4]

The risk of serotonin syndrome is higher if you take Trintellix with other medications that also affect your serotonin levels, such as other antidepressants, stimulants for ADHD, or the herbal supplement St. John’s Wort. But it can also occur when taking Trintellix alone, especially when you first start treatment or increase your dose. [4]

Serotonin syndrome symptoms can include:

  • confusion
  • irritability
  • anxiety
  • muscle spasms or tremors
  • diarrhea
  • fast heartbeat
  • high blood pressure {{4}]


Bleeding is a possible side effect when taking Trintellix and other antidepressants. While most bleeding episodes are minor, like a nosebleed, more serious internal bleeding can occur in rare cases. [4]

Trintellix seems to increase the risk of bleeding when combined with certain medications like aspirin, NSAIDs, or blood thinners. These drugs also raise bleeding risk, so using them with Trintellix may compound that effect. {{4}]

Symptoms of serious bleeding can include:

  • Hard-to-stop bleeding
  • Pink, red, or brown urine
  • Red or black stool
  • Coughing up blood
  • Vomiting what looks like coffee grounds [4]

Low Sodium Levels

Low sodium levels, also called hyponatremia, can occur in some people taking Trintellix. The FDA has found that fluid retention caused by a condition called syndrome of inappropriate antidiuretic hormone (SIADH) appears to be responsible for many of these cases. [4]

With SIADH, an area of the brain called the hypothalamus makes excessive amounts of antidiuretic hormone. This hormone controls the body's water balance. Too much antidiuretic hormone leads to increased water retention and diluted sodium levels. {{4}]

Older adults over 65 years of age have an increased risk of low sodium with Trintellix, as do those taking diuretic medications. [4]

Symptoms of low sodium can include:

  • Headache
  • Confusion
  • Weakness
  • Trouble concentrating [4]

Suicidal Thoughts

It’s important to know that Trintellix carries an FDA black box warning for increased suicidal thoughts and behaviors in children and young adults. A black box warning is the most serious warning administered by the FDA. It alerts doctors and patients about drug effects that may be dangerous. [4]

The black box warning indicates that Trintellix can heighten the risk of suicidal thinking and actions in younger people, though this risk does not seem to apply to older adults. Because of this increased risk, Trintellix is not approved for use in children. [4]

If you or a loved one are taking Trintellix, stay vigilant about worsening depressive thoughts or any suicidal thinking. Alert your doctor immediately if these symptoms arise so they can adjust treatment.

Sexual Problems

Sexual side effects are unfortunately quite common for both men and women taking antidepressants like Trintellix. During clinical trials, 16% to 29% of male participants and 22% to 34% of female participants experienced sexual side effects from Trintellix treatment. These numbers tend to rise when higher doses are taken. [5]

It's important to be aware of the potential sexual side effects of Trintellix, so you know what to expect and can discuss any concerns with your doctor.

Trintellix Drug Interactions

pharmacist holding medication packs and bottles

When starting a new medication, it's important to review potential drug interactions with your doctor. This helps avoid complications and ensures the medication works properly. Trintellix has some notable drug interactions to be aware of.

  • Monoamine oxidase inhibitors (MAOIs): The FDA warns that taking Trintellix within 14 days of stopping an MAOI or taking an MAOI within 21 days of stopping Trintellix increases the risk of serotonin syndrome. Serotonin syndrome causes dangerous symptoms like high fever, rigid muscles, confusion, and seizures. Examples of MAOIs include selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, and methylene blue.
  • Serotonergic drugs: Using Trintellix with other serotonergic medications can also increase serotonin syndrome risk. These include SNRIs, SSRIs, tricyclic antidepressants, fentanyl, lithium, tramadol, amphetamines, tryptophan, and St. John’s Wort. 
  • CYP2D6 inhibitors: Using Trintellix with CYP2D6 inhibitors can lead to high Trintellix plasma concentrations by preventing its breakdown. This further increases the risk of serotonin syndrome. Examples are bupropion, fluoxetine, paroxetine, and quinidine.
  • CYP inducers: These medications increase the speed at which the body breaks down Trintellix, potentially reducing its effectiveness. Examples of CYP inducers include rifampin, carbamazepine, and phenytoin.
  • Blood thinners: combining Trintellix with blood thinners like apixaban, aspirin, dabigatran, or warfarin raises the chance of stomach bleeding. [1]

If you are taking any of these medications, it is important to inform your doctor. They may need to adjust your Trintellix dosage, monitor you more closely for side effects, or consider alternative therapies to ensure your safety. [1]

Trintellix Usage During Pregnancy

pregnant woman holding her stomach

If you're pregnant or thinking about becoming pregnant, it's essential to consider how Trintellix may affect your pregnancy and the baby's development. Unfortunately, there have not been enough studies in humans to determine if Trintellix is entirely safe to use during pregnancy. Animal studies have suggested potential risks to fetuses exposed to the drug, though animal studies do not always translate to humans. [1]

Research on other antidepressants shows that use during pregnancy, especially in the third trimester, may lead to complications in newborns like difficulty breathing, seizures, irritability, and feeding problems. However, stopping Trintellix treatment during pregnancy can also have consequences, as depression symptoms may return. [1]

This is a complex situation with no easy answers. The risks of continuing or stopping Trintellix during pregnancy must be carefully weighed based on health conditions and circumstances. Your doctor can walk you through how Trintellix may impact your pregnancy and the development of your baby. Additionally, it’s important to have a conversation with your doctor about postpartum depression.


Trintellix is a valuable treatment option for those struggling with major depressive disorder when used appropriately under medical supervision. Being aware of potential side effects and avoiding dangerous interactions with other drugs is important. Healthcare providers can help monitor for adverse effects and adjust the dosage as needed.

To learn more about Trintellix, visit our Trintellix blog.

The content provided in this article is based on thorough research and in some cases, reviewed by a medical professional. Our goal for the information is to provide helpful, general health informational. It is not intended as a substitute for professional medical advice.