Is Trintellix an SSRI Medication and What About the Common Side Effects?

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Medically reviewed by, Russell Braun RPH

Trintellix is the brand name of a prescription only medication. The generic name is vortioxetine (although it is not available generically yet) and it is an antidepressant medication. Trintellix is approved by the Food and Drug Administration (FDA) for major depressive disorder (MDD).

Major depressive disorder lessens a person’s interest in activities of daily living. Some of the common effects of MDD include:

  • Loss of interest in normal activities
  • Sadness
  • Hopelessness
  • Fatigue
  • Anxiety
  • Weight gain
  • Suicidal thoughts

Trintellix could have many beneficial effects including improve your mood, sleep habits, appetitie, and increase energy levels. The goal in MDD is to bring back an interest in activities of daily living and Trintellix along with other SSRI’s can provide that outcome for some patients.

What is it called again?

When vortioxetine was first approved by the FDA in 2013 the brand name was Brintellix. However, the manufacturer changed the brand name to Trintellix in 2016 after the drug was reported to be confused with another brand name medication called Brilinta.

So is Trintellix an SSRI?

Trintellix is a selective serotonin reuptake inhibitor (SSRI). This class of drugs work by blocking the reuptake of serotonin in the spaces between neurons in the brain called synapses. In addition to blocking serotonin reuptake Trintellix seems to have effects on how the neurotransmitter is moved throughout the neurons as well.

Serotonin has a variety of effects in the body and can be tied to changes in mood, memory and cognitive function. Trintellix and many other drugs used to treat major depressive disorder have been proven effective by acting on serotonin levels in the brain.

What is different about Trintellix?

In addition to blocking serotonin reuptake, Trintellix has also been shown to affect the movement of serotonin in the neurons. This may explain benefits on the ability to think clearly (also called cognition) and some side effect differences between Trintellix and other SSRI’s.

Trintellix has also been shown to block receptors in the central nervous system known as 5-HT3, stimulate 5-HT1a receptors and impact other neurotransmitters, particularly glutamine and acetylcholine.

The exact effect these other actions have on treating depression are not fully understood. As with any drug for depression physical symptoms can start to improve in a few weeks but full response should not be expected for 8 weeks. This is due to the body changes that have to occur to relieve the depressive symptoms. Your brain actually had to make new reuptake receptors for serotonin in the neurons. This is the reason for the longer time to see full effect of the drug.

Is Trintellix an antipsychotic?

Many drugs classified as antipsychotics also work on the receptors mentioned above. However, most antipsychotics affect other receptors and neurotransmitters in the brain in addition to 5-HT1a and 5-HT3. Takeda Pharmaceuticals, the manufacturer of Trintellix have not requested FDA approval for the drug as an antipsychotic or to treat psychotic symptoms.

Is Trintellix an SNRI?

An SNRI differs slightly from an SSRI. Serotonin and Norepinephrine Reuptake Inhibitors (SNRI) act on two neurotransmitters in the brian and central nervous system. Trintellix is not an SNRI as it has not been shown to have effects on norepinephrine.

Is Trintellix good for anxiety?

Many patients who have Major Depressive Disorder will also experience anxiety. Anxiety that accompanies MDD is usually different than a diagnosis of full blown Generalized Anxiety Disorder (GAD). Trintellix may improve anxiety associated with MDD, but is not FDA approved for GAD.

Doctors sometimes prescribe drugs for “off label” uses. This simply means they use a drug for something that the FDA has not specifically approved it for. Many other SSRI’s are used to treat GAD off label. Some such as Paxil (paroxetine) also have FDA approval for GAD.

Don’t be surprised if your doctor offers Trintellix if you have MDD with GAD. Although it would be an off label use, it may still be effective. However, keep in mind there are many other SSRI’s that could also be used that are available generically and therefore much cheaper.

How much does Trintellix cost?

Before we talk about side effect difference between Trintellix and other SSRI’s it is important to note the cost difference. According to GoodRx a 30 day supply of the following SSRI’s are listed below.

SertralineAny$0 – $7

As you can see if you have to pay out of pocket with no insurance for Trintellix the cost is substantially more than other SSRI’s. Even with insurance it is likely that your copay will be higher than the $0 to $7 price for a therapeutic alternative that is available generically.

What are the side effects of Trintellix?

All medications come with a risk of side effects and they are dependent on the dose of the drug. Trintellix has been shown to have a side effect profile similar to other SSRI drugs, with a few exceptions.

The most common side effects from Trintellix include:

Side effectFrequency side effect occured
Nausea21% – 32%
Dizziness6% – 9%
Dry mouth7% – 8%
Constipation3% – 6%
Vomiting3% – 6%
Passing gas1% – 3%
Itchy skin1% – 3%
Abnormal dreams< 1% – 3%

As is true for almost all medications, side effects vary based on the dose taken. The table above shows side effect percentages for doses between 5mg to 20mg per day of Trintellix.

Compared to other SSRI drugs nausea seems to occur more frequently with Trintellix. In many cases this side effect will reduce in severity after a few weeks. However, nausea was the number one reason patients stopped taking Trintellix.

Sexual side effects

SSRI drugs are well known for causing problems with sexual drive and function. This occurs so often it was given its own name “treatment emergent sexual dysfunction” or TESD. Decreased desire or arousal and even a lack of ability to have an orgasm can all be part of TESD.

In many cases this side effect alone can cause patients to stop taking a depression medication. There is a need for medication that can continue to treat depression, with less TESD.

After a positive clinical trial on sexual side effects, the Food and Drug Administration (FDA) approved a labeling change for Trintellix. The label change suggested doctors could use Trintellix in patients who had TESD with other SSRI drugs. The trial showed that Trintellix was more effective than another SSRI, Lexapro also known generically as escitalopram, at improving TESD after patients switched from another SSRI that was causing them TESD.

What did the study look at?

Patients who had been treated and were having signs of improvement with depression symptoms were studied. The patients were taking either paroxetine, citalopram or sertraline and were switched to Trintellix or escitalopram the generic of Lexapro.

The patients took 10mg of either drug and increased to 20mg in one week. Trintellix showed a statistically significant improvement in TESD symptoms compared to escitalopram. The difference was based on a sexual functioning questionnaire that patients in the study completed. Both drugs proved to still be effective in treating the depression as well. What this means is that in a study looking at specific questions about how patients felt about sexual side effects there was a small difference between Trintellix and escitalopram.

Even though the difference in survey results from the trial were statistically significant, it does not mean the difference in TESD was that large overall. A slight improvement in a survey score doesn’t mean all sexual side effects disappear. The bottom line is that if you have TESD symptoms due to an SSRI, then escitalopram may improve the symptoms and Trintellix may due so slightly better.

Weight gain

There have been both short and long term studies looking at Trintellix effect on weight, ranging from 8 to 52 weeks. The doses ranged from 5-20mg in both the short and long term studies.

The short term study showed no clinically significant change in body weight compared to placebo. Keep in mind the study defined clinically significant as a 7% change in body weight. That means for an average 75 kilogram (165 pound) person, could gain 5 kilograms (11 pounds) and that would not have been considered weight gain in this study.

Long term studies defined clinically significant weight gain in the same way. They found that depending on dose from 11% to 13% of patients had clinically significant (more than 7%) weight gain. However, they also noted that 6% to 7.7% of the patients had clinically significant weight loss.

What should you believe?

Depression itself can cause people to gain or lose weight depending on the habits they acquire due to the depression. In addition, Americans gain an average of 1-2 pounds per year from early adulthood to middle age.

When using Trintellix to treat depression it is not likely to cause you to gain more weight than you may have otherwise. Remember that the studies done by the manufacturers of Trintellix make it sound like no weight gain occurred. If a 7% change in body weight seems significant to you even though they deemed it not clinically significant then you should talk with your doctor about how to deal with weight gain. Another great resource is the book The Serotonin Power Diet by Judith Wurtman.

Serious side effects

Suicidal thoughts

Antidepressants have been shown to increase the risk of suicidal thoughts and behavior. Depression and mental illness themselves can cause these feelings as well, but initiation of antidepressants can cause these thoughts to increase. This is especially true for children, teens and younger adults or when doses are changed. These thoughts should be taken seriously and reported to your doctor immediately.

Trintellix has a similar incidence of suicidal thoughts and behavior to other SSRI drugs.

Serotonin Syndrome

Trintellix, along with any drug that affects serotonin levels can have a rare, but very serious side effect called Serotonin Syndrome. When serotonin accumulates and levels get too high it can cause numerous symptoms and if left untreated could be fatal.

Some of the symptoms that are often overlooked include:

  • Easily irritated
  • Confused
  • Anxious
  • Shivering
  • Diarrhea

More severe symptoms that draw more attention and can be fatal if left untreated:

  • Fast heartbeat
  • High blood pressue
  • Muscle spasms
  • Tremors
  • Unexplained fever
  • Seizures

Patients on Trintellix should be on the lookout for serotonin syndrome in the following situations:

Typically symptoms of serotonin syndrome will go away after stopping the medications. However, Serotonin syndrome is serious and you should always talk to your doctor if you think you are having symptoms. Calling 911 is a good idea if displaying any of the more serious symptoms.


Trintellix can cause bleeding when used in conjunction with other medications such as aspirin, nonsteroidal anti-inflammatory drugs also called NSAIDs and other blood thinning drugs.

The bleeding can range from minor nosebleeds to more serious internal bleeding. If you suspect you are having a bleeding issue you should call your doctor right away and let them know you take Trintellix along with other medications and supplements you take.

Common symptoms of bleeding include:

  • Nosebleeds
  • Stools that are either bright red or black and tar looking
  • Pink or red urine
  • Coughing up blood
  • Coughing up or vomiting blood clots

Final thoughts

Trintellix is an effective, yet very costly medication to treat depression and may be a good option for patients prone to sexual dysfunction side effects. Weighing it’s cost and potential benefit with sexual dysfunction versus other treatment options will provide the best outcome for you.

You should check Needymeds.org to find patient assistance programs for Trintellix. In addition, Takeda pharmaceuticals offers a copay coupon to help offset patient costs for Trintellix.

Click here to get Dr. Jason Reed’s exclusive list of medication questions you MUST ask your doctor, for FREE!

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