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Key takeaways
Trintellix is an antidepressant used to treat symptoms of major depressive disorder (MDD).
Although Trintellix works along serotonin receptors in your brain, it’s not an SSRI—it’s a serotonin modulator, and has a somewhat different side effect profile than many SSRIs.
The most common side effects when starting Trintellix include nausea, vomiting, and dizziness. These side effects often go away as your body adjusts to the medication, and most people on maintenance doses don’t have persistent symptoms.
Trintellix (vortioxetine) is an antidepressant approved for use in treating major depressive disorder (MDD). It’s usually categorized as a serotonin modulator, which is similar to selective serotonin reuptake inhibitors (SSRIs) but not exactly the same. Trintellix also has a slightly different side effect profile than some other common SSRIs, like Zoloft (sertraline) and Prozac (fluoxetine), often causing less weight gain but more gastrointestinal distress.
Here’s what to know about the side effects of starting Trintellix, including how to manage them, when they might improve, and when to contact your healthcare provider.
What is Trintellix used for?
In 2013, the Food & Drug Administration approved Trintellix for use in treating symptoms of MDD, a severe and often chronic form of depression. But it is sometimes prescribed off-label for some anxiety disorders.
Trintellix is a serotonin modulator that works in two ways: by increasing serotonin levels in your brain, and by making that serotonin more available to be used by your brain. According to Jasmine Kaur, MD, psychiatrist with Mindpath Health, this makes Trintellix a multimodal antidepressant, especially since it also increases the levels of several other neurotransmitters in the brain, too, including norepinephrine.
What to know about starting Trintellix
If you’re thinking about starting Trintellix or have just begun taking this medication, you might be wondering what to expect as far as dosage and timing. Although individual treatment plans vary, here’s a general idea of what to expect when starting Trintellix.
Trintellix starting dose
According to Dr. Kaur, a typical dose of Trintellix is between 5 and 20 milligrams (mg), with most people starting at five or 10 mg and slowly increasing from there, if needed.
“A maintenance dose depends on various factors, including your response to the medication, any interactions with other medications, and potential side effects,” Dr. Kaur explains.
How long does it take Trintellix to start working?
Trintellix takes about as long to start working as most other antidepressants do. Dr. Kaur says you might start noticing an improvement in your symptoms after two to three weeks, but it usually takes four to eight weeks before the medication is working at its full potential.
Trintellix side effects
All antidepressants carry a risk of side effects, and Trintellix is no different. That said, as a serotonin modulator, Trintellix is known for potentially causing somewhat different side effects than some other common antidepressants.
Trintellix side effects when starting
There’s a wide range of potential side effects when it comes to starting Trintellix. Nick Bach, Psy.D., a licensed clinical psychologist in Louisville, Kentucky, says his patients have described everything from mild and temporary to challenging or persistent side effects, with the most common one being nausea.
In clinical trials of Trintellix, about 25% of people experienced nausea. However, the nausea is often the worst when you first start taking Trintellix. In those same trials, only around 10% of people were still reporting nausea after being on the medication for six to eight weeks.
Dr. Bach says you may be able to relieve some of the initial nausea after starting Trintellix by taking your dose with food, splitting up the dose, or adjusting the timing of your dose. Some people may also have cognitive side effects, like dizziness and brain fog, which also usually go away as your body adjusts to the medication, according to Dr. Bach.
Everyone is different, though, and University of Missouri Health Care psychiatrist Ashish Sarangi, MD, says your dose can play a role in the severity of your symptoms, with higher doses causing more side effects. For example, in the Trintellix clinical trials, the 10% of people still experiencing nausea after six to eight weeks on the drug were taking a dose between 10 and 20 mg (as opposed to 5 mg).
Some other common side effects of starting Trintellix, per Dr. Sarangi, include:
- Vomiting
- Diarrhea
- Dry mouth
- Fatigue
- Headaches
- Sexual dysfunction, like decreased libido or difficulty achieving orgasm
Trintellix side effects over time
If you need to increase your dose of Trintellix, your healthcare provider will help you do this slowly and safely, minimizing side effects, until you reach a maintenance dose. At that point, some of your side effects may lessen or go away, but others could persist.
For example, Dr. Sarangi says many of the more common side effects, especially the GI symptoms like nausea, tend to go away a few weeks after a new dose is started. Other side effects, like dry mouth, dizziness, and headaches, may also go away the longer you’re on Trintellix. Sexual side effects, however, can take longer to go away and could even continue for as long as you’re on the medication, she notes.
That said, Trintellix is often associated with fewer side effects than other antidepressants. A 2024 study even shows an improvement in sexual dysfunction in people switching to Trintellix after experiencing serious sexual dysfunction while taking other antidepressants.
If your side effects don’t get better over time or are affecting your quality of life, talk to your healthcare provider. There may be another medication you can take to manage your MDD symptoms that doesn’t cause persistent side effects for you.
Trintellix missed dose side effects
Most people won’t experience any severe symptoms from missing a single dose of Trintellix, according to Dr. Bach. Unlike SSRIs, Trintellix has a relatively long half-life of about 66 hours, so it stays in your system for a while, and a missed dose isn’t likely to cause immediate withdrawal symptoms. But some people will experience mild dizziness, nausea, or mood changes from missing a dose.
“Repeatedly missing or skipping doses, however, can not only cause withdrawal symptoms like headache, irritability, or worsening depression, but also lower Trintellix’s effectiveness in treating your symptoms,” Dr. Sarangi says.
If you miss a dose of Trintellix, Dr. Sarangi recommends taking it as soon as you remember unless it’s closer to your next dose. In that case, skip the missed dose and take your next dose on your regular schedule. It’s important to never double your dose or take two doses of an antidepressant close together, as this can increase your risk of side effects.
When to see a doctor for Trintellix side effects
While side effects like nausea, vomiting, brain fog, and dry mouth are common when first starting Trintellix, it’s important to know the difference between normal side effects and potentially serious side effects or allergic reactions.
Dr. Sarangi says you should contact your healthcare provider or seek emergency medical attention if you experience any of the following after starting Trintellix:
- Severe nausea or vomiting that doesn’t improve
- Worsening depression or suicidal thoughts
- Symptoms of serotonin syndrome, like agitation, confusion, rapid heart rate, muscle rigidity, or fever
- Symptoms of a severe allergic reaction, like rash, swelling, or difficulty breathing
- Persistent sexual dysfunction that impacts your quality of life
Although it can be frustrating to cope with side effects like GI distress or brain fog when starting a drug like Trintellix, you should never suddenly stop taking it or change your dose without talking to your healthcare provider first. Doing so can increase your risk for additional side effects, according to Dr. Sarangi, including:
- Withdrawal symptoms like dizziness, irritability, anxiety, and headache
- Worsening depression or anxiety symptoms
- Interactions with other medications you’re taking or treatments you’re undergoing
If you want to stop taking Trintellix or lower your dose, your healthcare provider will work with you to taper it gradually in an effort to limit side effects and help your body readjust to the changing levels of medication in your system.
- Serotonin modulator antidepressants, Elsevier (2024)
- Major depressive disorder, StatPearls (2023)
- Trintellix highlights of prescribing information, Food and Drug Administration (2023)
- Switching to vortioxetine in patients with poorly tolerated antidepressant-related sexual dysfunction in clinical practice: A 3-month prospective real-life study, Journal of Clinical Medicine (2024)