If you notice any of the following, contact your doctor right away:

• Serotonin syndrome
• Serious bleeding
• Low sodium levels
• Suicidal thoughts [1]

Serotonin Syndrome

When taking Trintellix, it's important to be aware of the risk of serotonin syndrome. This is a condition that can occur when there is too much serotonin building up in your body. [3]

Trintellix works by increasing serotonin levels in the brain, which can be helpful for depression. However, sometimes this serotonin boost can become too high. This is especially likely if you are also taking other medications or supplements that raise serotonin, like other antidepressants, ADHD stimulants, or St. John's Wort. But even Trintellix alone can potentially lead to too much serotonin in some cases. [3]

Symptoms of serotonin syndrome can range from mild to severe. Milder symptoms include:

• Agitation
• Anxiety
• Restlessness
• Disorientation
• Increases sweating
• Fast heartbeat
• Nausea
• Vomiting
• Muscle tremors or rigidity [3]

Symptoms of severe serotonin syndrome include:

• Seizures
• Irregular heartbeat
• Unconsciousness [4]

Serious Bleeding

While taking Trintellix, some people may experience increased bleeding. In most cases, this bleeding is minor, such as a nosebleed. However, more serious internal bleeding is possible in rare cases. [1]

Trintellix increases the risk of bleeding when combined with certain other medications that also increase bleeding risk. These include aspirin, NSAIDs like ibuprofen, and blood thinners like warfarin. Using Trintellix with these types of drugs may compound the bleeding risk. [1]

It's important to watch for signs of serious bleeding while taking Trintellix. Symptoms to look out for include:

• Hard-to-stop bleeding
• Pink, red, or brown urine
• Red or black stool
• Coughing up blood
• Vomiting what looks like coffee grounds [1]

Low Sodium Levels

Low sodium levels, also known as hyponatremia, can occasionally occur in those taking Trintellix. Research has found that fluid buildup caused by a condition called syndrome of inappropriate antidiuretic hormone (SIADH) is the culprit in many cases. [1]

With SIADH, the brain's hypothalamus region makes too much antidiuretic hormone, which regulates the body's fluid balance. Excess antidiuretic hormone leads to increased water retention and diluted sodium levels. [5]

Certain groups have a higher risk of low sodium with Trintellix use, including adults over 65 and those taking diuretic medications. [1]

Mild symptoms of hyponatremia can include

• Nausea
• Vomiting
• Fatigue
• Headache
• Muscle cramps [5]

Symptoms of severely low sodium levels include:

• Disorientation
• Agitation
• Coma
• Seizures [5]

Suicidal Thoughts

The FDA has given Trintellix a black box warning due to increased risks of suicidal thoughts and behaviors in children and young adults taking the medication. A black box warning is the most serious type of warning from the FDA, signaling significant risks that patients and doctors must be aware of. [1]

If you or a loved one are taking Trintellix, it's essential to monitor for any worsening of depressive thoughts or the emergence of suicidal thinking. Contact your doctor immediately if these symptoms arise so they can adjust treatment as needed. While on this medication, be on the lookout for changes in mood and thinking that could lead to suicidal behaviors. Stay vigilant and report any concerns immediately.

Trintellix Drug Interactions

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): Do not take Trintellix within 14 days of stopping a monoamine oxidase inhibitor (MAOI) antidepressant or take an MAOI within 21 days of stopping Trintellix. Combining these can cause serotonin syndrome, a potentially life-threatening condition with symptoms like high fever, stiff muscles, confusion, and seizures. MAOIs include selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, and methylene blue.

• Serotonergic drugs: Taking Trintellix alongside other serotonergic medications may increase your risk of serotonin syndrome. These include SNRIs, SSRIs, tricyclic antidepressants, fentanyl, lithium, tramadol, amphetamines, tryptophan, and St. John’s Wort. 

• CYP2D6 inhibitors prevent the breakdown of Trintellix, leading to high amounts in the blood and further raising serotonin syndrome risk. Examples include bupropion, fluoxetine, paroxetine, and quinidine.

• CYP inducers like rifampin, carbamazepine, and phenytoin speed up Trintellix breakdown, potentially making it less effective.

• Blood thinners: combining Trintellix with blood thinners such as apixaban, aspirin, dabigatran or warfarin increases the chance of stomach bleeding.[1]

Trintellix Withdrawal

If you have been taking Trintellix and wish to stop taking it, talk to your doctor first. Stopping Trintellix abruptly can lead to withdrawal side effects such as:

• Irritability
• Sudden worsening of mood
• Nervousness
• Agitation
• Muscle tension
• Headaches [1]

Your doctor will consider your current Trintellix dosage and create a plan to lower and discontinue it gradually. This helps your body adjust slowly to avoid withdrawal effects.

• If you take 15 to 20 mg of Trintellix daily, your doctor may have you decrease it to 10 mg daily for at least a week before entirely stopping.

• If you have been on a lower daily dose of 10 mg or 5 mg, it may be possible to discontinue Trintellix without tapering. However, it is still advisable to consult your doctor before changing your medication regimen. [1]

Trintellix During Pregnancy

If you are pregnant or planning to conceive, it is crucial to consider the potential effects of Trintellix on your pregnancy and your baby's development. Unfortunately, due to insufficient human studies, the question of whether Trintellix is entirely safe to use during pregnancy remains uncertain. While animal studies have indicated potential risks to fetuses exposed to the drug, it is important to note that findings from animal studies do not always directly translate to humans. [1]