Key takeaways

Trintellix (vortioxetine) is used to treat major depressive disorder and has common side effects including nausea, diarrhea, dry mouth, dizziness, and sexual dysfunction.
Trintellix has less of an effect on weight than other antidepressants, but weight changes are possible and will vary by person, although they tend to be minimal. One study found people who took Trintellix gained one pound over a one-year period.
Discontinuation of Trintellix should be gradual to prevent withdrawal symptoms such as nausea, sweating, and dizziness.
Trintellix can interact with MAO inhibitors, serotonergic drugs, and blood thinners, increasing the risk of serious side effects like serotonin syndrome and bleeding problems.

Trintellix (active ingredient: vortioxetine) is a brand-name prescription drug that treats major depressive disorder (MDD) and sometimes prescribed off-label to treat anxiety. Vortioxetine, the active ingredient in Trintellix, balances serotonin 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.

Common side effects of Trintellix

The most common side effects of Trintellix are:

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

Drowsiness is not known to be a common side effect of vortioxetine. Instead, vortioxetine may improve sleep cycles and help reduce daytime drowsiness.

Trintellix weight changes

Antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), are known for being associated with weight gain, but whether they actually cause weight gain is far from certain. Trintellix, on the other hand, appears to have minimal effects on body weight. In clinical studies that followed patients over six months, Trintellix, then called Brintellix, had no significant effects on body weight. A later year-long study, however, showed patients gained an average of one (1) pound while on Trintellix. 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 all medications that affect serotonin in the brain, Trintellix should not be discontinued abruptly. Although the drug is not addictive, the dose should be gradually decreased over several weeks before stopping to prevent discontinuation symptoms. The most common Trintellix discontinuation symptoms are:

Nausea
Sweating
Agitation
Irritability
Dizziness
Anxiety
Confusion
Insomnia

Discontinuation syndrome symptoms may take a few hours to three days to appear and may persist for one or two weeks. Usually, these symptoms resolve without treatment in one to two weeks.

Serious side effects of Trintellix

Trintellix can cause serious side effects including:

Suicidal thoughts and behaviors
Serotonin syndrome
Bleeding problems
Mania or hypomania in patients with bipolar disorder
Angle-closure glaucoma
Low sodium levels
Severe allergic reactions, including anaphylaxis or angioedema

Suicide

Trintellix comes with an FDA black box warning that children, adolescents, and young adults are at an increased risk of suicidal thoughts and behaviors. When taking Trintellix, younger patients should be closely monitored for signs of suicidality such as:

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

Serotonin syndrome

Antidepressants like vortioxetine may cause serotonin syndrome, a potentially hazardous condition caused by too much serotonin in the brain. Discontinue Trintellix immediately and seek medical care at 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 concentration of salt (sodium) in the blood to fall, a condition called hyponatremia. Low blood sodium can be a serious and potentially hazardous medical condition, so seek medical care at signs of hyponatremia including:

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

Angle-closure glaucoma

Angle-closure glaucoma 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

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

How long do Trintellix side effects last?

The most common Trintellix side effects are temporary and will usually fade within a few days after the medication is discontinued. Severe side effects, however, may take longer to resolve. Mild cases of serotonin syndrome typically resolve within two 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 a variety of reasons, some people may not be able to take the medication while others may need to be cautious before starting it.

Allergies

Anyone with severe allergies to Trintellix should not take the medication.

MAO inhibitors

People taking monoamine oxidase inhibitors (MAOIs), a class of drugs that includes some types of antidepressants, antibiotics, or drugs that treat Parkinson’s disease, will not be prescribed Trintellix until they have stopped taking MAO inhibitors for at least 14 days.

Poor metabolizers

Some people don’t break down vortioxetine very well. The drug then lingers for a longer time in the body at higher concentrations, increasing the risk for side effects. Fortunately, people can be genetically tested. Poor metabolizers will be restricted to a maximum daily dose of 10 milligrams (mg).

Children

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

Seniors

In clinical trials, Trintellix has been shown to be effective and safe in patients older than 65. No dose adjustment is required.

Pregnancy and breastfeeding

There is not enough research or information determining that Trintellix is safe to take during pregnancy. People who are pregnant or considering pregnancy should seek medical advice from a healthcare professional before starting or discontinuing Trintellix.

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 cause a variety of adverse effects.

Trintellix and MAO inhibitors

Trintellix should not be taken with monoamine oxidase inhibitors (MAOIs). Combining Trintellix with an MAO inhibitor may cause serotonin syndrome. These drugs include:

Parnate (tranylcypromine)
Marplan (isocarboxazid)
Nardil (phenelzine)
Zyvox (linezolid)
Sivextro (tedizolid)
Emsam (selegiline)
Xadago (safinamide)
Methylene blue injections

Trintellix and serotonergic drugs

Drugs that elevate serotonin levels are called serotonergic drugs. Some of these medications have a big effect on serotonin, while others do not. The risk for serotonin syndrome is very low but increases when two or more serotonergic drugs are taken together. For this reason, combining other serotonergic drugs with Trintellix is to be avoided. These include:

Antidepressants such as
- Tricyclic antidepressants
- SSRIs (selective serotonin reuptake inhibitors), such as citalopram, paroxetine, sertraline, or fluoxetine
- SNRIs (selective serotonin and norepinephrine reuptake inhibitors), such as duloxetine or venlafaxine
- Wellbutrin (bupropion)
Anxiety medications such as buspirone
Stimulants
Drugs that treat or prevent nausea
Cough medicines containing dextromethorphan
Migraine medications including triptans and ergot drugs
Opioids such as tramadol or fentanyl
Antipsychotics
Anticonvulsants such as carbamazepine or phenytoin
Parkinson’s medications
Lithium
Herbal supplements such as St. John’s wort, tryptophan, or Yohimbe

Trintellix and blood thinners (anticoagulants)

Trintellix raises the risk of bleeding problems, so therapy will need to be monitored if a person is also taking blood-thinners, such as warfarin or Plavix (clopidogrel). Nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen, also interfere with blood clotting, so they should be used sparingly when taking Trintellix. Some anticancer drugs also raise the risk of bleeding episodes when taken with Trintellix. Finally, steroids can cause gastrointestinal bleeding. The risk of bleeding problems increases when these medications are taken with Trintellix.

Many people are unaware that some popular dietary and herbal supplements interfere with blood clotting, so these, too, should be used sparingly when taking Trintellix. They include:

Garlic
Ginkgo
Krill oil
Saw palmetto
Willow bark

Trintellix and diuretics

Trintellix raises the risk of low sodium levels in the blood. Diuretics (water pills) could contribute to the problem by increasing the excretion of sodium. Therapy with diuretics may need to be monitored or modified. Sulfonylurea drugs, prescribed to control blood sugar in patients with type 2 diabetes, will also increase the risk for low sodium in people taking Trintellix.

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 types of anticonvulsant drugs
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 incidence and severity of possible side effects. These include:

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

A healthcare provider may need to decrease the Trintellix dose by as much as half when taken with these medications.

Trintellix and alcohol

There is no evidence drinking alcohol will cause additional impairment while taking vortioxetine. The manufacturer, however, advises individuals to avoid drinking alcohol while taking 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 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 be working or side effects are hard to take, talk to the prescribing physician, a 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 the dose according to your healthcare provider’s instructions.

3. Do not miss doses

Like all antidepressants, people get less benefit from the medication if they miss doses. If too many doses are missed in a row, symptoms of the condition being treated may return. It is helpful to keep a medication diary, use a medication app, set up a seven-day pillbox, or set an alarm for each day’s dose.

4. Tell the doctor about all medical conditions

Sharing a full medical history can help prevent side effects. Before starting Trintellix, tell your doctor if you have had any of the following:

A history of seizures
Any problems with low sodium
Any problems with bleeding
Mania or bipolar disorder
Glaucoma

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

5. Tell the doctor about all medications being taken

Trintellix has several adverse effects due to drug interactions. Tell the prescribing doctor about all the medications and supplements you take, particularly:

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
Rifampicin
Quinidine
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 talking to a healthcare professional.

Resources:

Antidepressant discontinuation syndrome, American Family Physician
Trintellix, Epocrates
Trintellix Medication Guide, Takeda Pharmaceuticals
Vortioxetine, StatPearls
Vortioxetine (Trintellix), National Alliance on Mental Illness (NAMI)
Antidepressant utilisation and incidence of weight gain during 10 years’ follow-up; population based cohort study, BMJ
Antidepressants cause minimal weight gain, Harvard Health
Depression, StatPearls
Drug-induced serotonin syndrome, U.S. Pharmacist
Major Depressive Disorder, StatPearls
“Narrow angles” a tip-off to eyesight risk, Harvard Health
Vortioxetine, Lactation and Drug Database
Vortioxetine compound summary, National Library of Medicine
Weight gain and antidepressants, Journal of Clinical Psychiatry