Get $25 Off On Subscription Orders!

Trintellix Review: Is It The Safest Antidepressant?

Trintellix Review: Is It The Safest Antidepressant?

| |
Read our Editorial Guidelines to learn more about what makes our site the premier resource for online health information.
| |
Read our Editorial Guidelines to learn more about what makes our site the premier resource for online health information.

Read our Editorial Guidelines to learn more about what makes our site the premier resource for online health information.

 Disclaimer: None of the information in this article constitutes medical advice, and is just the opinion of the writer(s). We recommend that patients follow their doctor’s guidance in regards to prescription medication.

Trintellix is a prescription drug primarily used to treat depressive disorder. It’s a relatively novel drug, having been approved by the Food and Drug Administration (FDA) in the U.S. to treat major depressive disorder in 2013.

The generic version of Trintellix is called vortioxetine, and we will use these two terms interchangeably throughout this article as they refer to the same active chemical compound.

In this article we’ll review the medical research on Trintellix to determine if it’s safe and effective for treating depression, and offer a natural non-prescription alternative that patients may want to speak to their doctor about.

Does Trintellix Work? 

An extensive medical review was published in the Cochrane Library in 2017 evaluating the efficacy of Trintellix for treating depression. The study authors examined the data in 15 individual clinical trials which used Trintellix to treat depression. 7,746 individual patients were included in those studies.

The researchers found that Trintellix was more effective than placebo in treating depression on average, but that the “quality of evidence” to support its effectiveness was “generally low.” The quality of evidence was suggested to be low due to methodological flaws in some of the studies which could have resulted in poor-quality data.

A 2015 clinical trial tested the efficacy of Trintellix for treating major depressive disorder, which is the use that the drug was approved by the FDA for. Unsurprisingly, the drug was found to be effective in the study.

Patients reported symptoms of depression in a standardized format called the Montgomery-Asberg Depression Rating Scale (MADRA), and their reported symptoms dropped substantially after 8 weeks of Trintellix treatment. 39% of patients on a higher dose achieved symptom relief, and 22% achieved full remission of symptoms.

A more recent study evaluated Trintellix for patients with major depression and anxiety. Researchers found the drug to be effective for reducing both depression and anxiety scores on average.

We can conclude from the available research that Trintellix is effective for treating depression, and may be effective for treating anxiety as well in depressed patients.

How Does Trintellix Work?

Unlike most common antidepressants, the exact mechanism of action of Trintellix isn’t completely understood by researchers. 

It appears chemically similar to a Selective Serotonin Reuptake Inhibitor (SSRI) drug, as evidenced by this medical review, but it also directly modulates serotonin receptors, which is something standard SSRIs don’t do.

Serotonin is a neurotransmitter that affects mood and can impact depression. Researchers theorize that low levels of serotonin in the brain may cause depression, and SSRIs artificially increase circulating serotonin levels in the brain, thus alleviating symptoms.

Trintellix appears to work by increasing serotonin levels, but more research is needed to confirm this.

Trintellix Side Effects

When evaluating a pharmaceutical drug, it’s important to weigh the potential benefits against the side effects.

Trintellix has been shown to cause side effects in patients. A medical review on the safety and tolerability of the drug, which analyzed extensive patient aggregate data, found nausea to be the most common side effect, affecting around 20% of patients.

Headache was the second-most common side effect, affecting 12% of patients. Diarrhea was third and affected around 7% of patients.

Patients had to discontinue the medical trials about 3% of the time (more than placebo) due to severe side effects from Trintellix.

Interestingly, this review found that the rate of suicidal behavior was no higher for patients on Trintellix than placebo, even though the drug has a black box warning on its label about increased risk of suicidal thoughts and behaviors. 

This makes us wonder if Trintellix is forced to use a black box warning on its label by the FDA just because it’s chemically similar to SSRIs, and not because of patient data proving it causes increased suicide risk.

Trintellix Dosage

Trintellix is approved at doses ranging between 5 milligrams (mg) and 20 mg daily. Patients typically start at the lower dosage, and then dosage may be increased if the patient isn’t seeing symptom relief after a few weeks.

The previously-linked study on Trintellix for major depressive disorder directly compared the effects of the drug at 10 mg and 20 mg, and found that the 20 mg dose was more effective. In fact, researchers noted that only the 20 mg dose was more effective to a statistically significant degree (meaning the effects are likely caused by the drug and not randomness) than placebo treatment.

More patients experienced side effects in every symptom category other than headache at the 20 mg dose than the 10 mg dose, according to the previously-linked safety and tolerability review.

Should I Take Trintellix Generic?

We recommend generic drugs because medical research proves them to be just as effective as brand name drugs, and often significantly cheaper. 

The generic version of Trintellix is called vortioxetine. These two names refer to the exact same active chemical compound with antidepressant effects.

Switching to generic from brand-name drugs may save hundreds or even thousands of dollars a year, so we recommend especially that patients on a lower income speak to their doctor about this option, if their doctor only suggested the brand-name version of the drug.

Trintellix and Cognition

Trintellix has an interesting secondary benefit to depressed patients which we haven’t seen in other antidepressants we’ve reviewed: it may improve cognition.

Mental conditions such as anxiety and depression are often associated with transiently decreased cognition. Trintellix seems to ameliorate this issue in depressed patients.

A meta-review published in the Drugs journal found that for adults with major depression, Trintellix “almost always resulted in statistically significant and clinically meaningful improvements” on cognitive functioning. The study authors suggested that the drug may be especially useful to patients where impaired cognitive function has resulted from their condition.

Researchers haven’t yet clarified what causes this beneficial effect, but it does appear to be legitimate as multiple studies reported the same effect.

Trintellix Vs. Zoloft

There has been a head-to-head comparison in a medical trial between two of the most prescribed antidepressants. We recently published a Zoloft review, and came across an interesting medical study on Trintellix Vs. Zoloft.

The study was published in 2020, and compared the two drugs on an elderly population with major depressive disorder.

The two drugs were nearly identical in terms of efficacy and safety.

A more broad antidepressant review published in a leading journal found that Trintellix had a superior remission rate (percentage of patients with full relief from all depression symptoms) than Zoloft, and also caused a lower percentage of patients to drop out of medical trials than Zoloft.

It appears based on our research that Trintellix is as effective and slightly safer than Zoloft, especially considering that Trintellix wasn’t shown in an extensive meta-study to increase risk of suicide.

Natural Alternative

Magnesium is a mineral that much of the American population is deficient in. It’s been shown in medical research to help relieve symptoms of depression, and has no serious side effects.

A medical review concluded that “magnesium preparations seem to be a valuable addition to the pharmacological armamentarium for the management of depression.”

Another review published in the Medical Hypotheses journal documented case reports of patients experiencing rapid recovery of depression from magnesium supplementation. Doses of 125 - 300 mg per meal were used, and the researchers suggested that intraneuronal magnesium deficits could be a driver of depression.

For depressed patients with the income, getting an intracellular nutrient test may provide valuable information. The vast majority (99%+) of magnesium is not stored in blood, so standard red blood cell magnesium tests can fail to document subclinical deficiencies.

For those who want to try a magnesium supplement, we recommend a chelated version like magnesium glycinate or magnesium taurate, as these have been proven to be better-absorbed than cheaper forms like magnesium oxide, and the chelated versions were used in the linked research.

Magnesium can also be supplemented transdermally, through skin application, by either Epsom salt baths or magnesium oil application to the skin. Both forms use magnesium sulfate as the active ingredient, which is proven to absorb through the skin into the bloodstream.

Stay up-to-date on our research reviews


Trintellix is effective for treating depression and it may be able to restore cognitive function in patients who are severely depressed and have suffered cognitively due to their condition.

One benefit of Trintellix over most SSRIs is it doesn’t appear to cause an increase in suicide risk, even though the FDA requires the label disclosure because of the class of drugs it’s in.

We recommend vortioxetine, which is the generic form of Trintellix, over the brand name version for cost reasons.

Patients who are interested in a more natural treatment of depression with fewer side effect risks may want to speak to their doctor about magnesium supplementation.

Liquid error: Could not find asset snippets/search-bar.liquid