Trintellix (vortioxetine) is an antidepressant used to treat major depressive disorder, and nausea is by far its most common side effect. In clinical trials, nausea affected roughly 20% to 30% of people taking it, depending on the dose. Most side effects are mild and improve within the first few weeks, but there are some less common reactions worth knowing about.
Nausea and Digestive Side Effects
Nausea is the side effect most people notice first, and it’s the top reason people stop taking Trintellix. It tends to be worst during the first week or two and typically fades as your body adjusts. Other digestive issues include vomiting, diarrhea, and constipation, though these are less frequent than the nausea itself.
If nausea is a problem, taking Trintellix right after a large meal can help. One strategy recommended by psychiatrists is to take a ginger capsule (1,000 to 2,000 mg) on an empty stomach about an hour before eating, then eat a full meal, then take the medication on top of that. The ginger settles the stomach, and the food creates a buffer so the drug is less irritating. Timing the dose with dinner rather than breakfast works well for many people since you can sleep through the worst of it.
Sexual Side Effects
One of the reasons Trintellix stands out from older antidepressants is its lower rate of sexual side effects. The Mayo Clinic lists vortioxetine among the antidepressants least likely to cause sexual dysfunction, while common SSRIs like sertraline (Zoloft), fluoxetine (Prozac), and paroxetine (Paxil) are among the most likely. That said, “lower risk” doesn’t mean zero risk. Some people still experience reduced sex drive, difficulty with arousal, or trouble reaching orgasm. If you switched to Trintellix specifically because of sexual side effects on another antidepressant, give it a few weeks to see how you respond.
Increased Bleeding Risk
Trintellix can interfere with how your blood clots, which may lead to easier bruising or, in rare cases, more serious bleeding. This matters most if you’re also taking blood thinners, aspirin, or common pain relievers like ibuprofen (Advil) or naproxen (Aleve). Signs to watch for include unusual bruising, blood in your stool or urine, or bleeding that takes longer than normal to stop. The risk is low for most people, but it’s worth mentioning to your prescriber if you regularly take any of those medications.
Low Sodium in Older Adults
Trintellix can occasionally cause a drop in blood sodium levels, a condition called hyponatremia. This is primarily a concern for people over 65. Risk factors include being female, having low body weight, kidney or heart problems, and taking diuretics (water pills). Symptoms of low sodium include headache, confusion, difficulty concentrating, and weakness. In severe cases it can cause seizures. The exact frequency of this side effect with Trintellix isn’t well established because the drug is relatively new, but it’s a known risk with all antidepressants that affect serotonin.
Serotonin Syndrome
Serotonin syndrome is a rare but serious reaction that happens when too much serotonin builds up in your body. It’s most likely to occur when Trintellix is combined with other medications that also raise serotonin levels, such as other antidepressants, certain migraine medications (triptans), or the herbal supplement St. John’s wort. Symptoms include agitation, rapid heartbeat, high body temperature, muscle twitching or stiffness, and loss of coordination. This is a medical emergency. If you experience a cluster of these symptoms, especially after starting a new medication alongside Trintellix, seek immediate care.
Suicidal Thoughts in Young Adults
Like all antidepressants, Trintellix carries an FDA black box warning about an increased risk of suicidal thoughts and behavior in people under 25. In pooled clinical trials involving over 77,000 adults and 4,500 younger patients, those under 18 had 14 additional cases of suicidal thoughts per 1,000 patients compared to placebo. For 18 to 24 year olds, the increase was 5 additional cases per 1,000. In adults 25 and older, antidepressants did not increase this risk and in people over 65, there were actually 6 fewer cases per 1,000.
This risk is highest during the first few months of treatment and around dose changes. It doesn’t mean the medication causes suicidal behavior in most people. It means that mood shifts, especially early on, need close attention. If you notice a sudden worsening of mood, new feelings of agitation or restlessness, or thoughts of self-harm after starting or adjusting Trintellix, reach out to your prescriber promptly.
Withdrawal When Stopping
Stopping Trintellix abruptly can trigger withdrawal symptoms, though not everyone experiences them. Common ones include headache, dizziness, nausea, irritability, muscle tension, sweating, trouble sleeping, and fatigue. Some people also report tremor or nervousness. If you’re on 15 mg or 20 mg daily, the recommended approach is to step down to 10 mg for one week before stopping completely. This taper helps your brain adjust gradually rather than losing the drug’s effects all at once.
Withdrawal symptoms are generally short-lived, but their severity and duration vary from person to person. If you’re planning to stop Trintellix, work with your prescriber on a schedule rather than quitting cold turkey.