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Key takeaways
Side effects from medications are not unusual. While Trintellix may cause many serious side effects like increased risk of bleeding, activation of hypomania, hyponatremia (low sodium levels), suicidal thoughts, and ocular effects like glaucoma, nausea is the common side effect associated with Trintellix, followed only closely by sexual side effects.
Many antidepressant drugs cause nausea to some degree, including SSRIs, SNRIs, monoamine oxidase inhibitors (MAOIs), and tricyclic antidepressants (TCAs). Other psychiatry medications, including lithium, can do the same.
Nausea associated with Trintellix tends to resolve over the first few weeks of therapy, as the body adapts to new levels of circulating serotonin. Seek medical advice for guidance on supplements or other medications that may help you get through those first weeks of therapy, as certain health conditions may make some options more desirable.
Trintellix (vortioxetine) is a brand-name antidepressant in the selective serotonin reuptake inhibitor/5-HT1A receptor partial agonist drug class and is an important contribution to the armamentarium of mental health prescription drugs. It is approved by the Food and Drug Administration (FDA) for the management of major depressive disorder (MDD). Trintellix may be more desirable to some afflicted with depression over other drug classes since it is associated with reduced risk of weight gain and sexual dysfunction in comparison to more traditional antidepressants like SSRIs and SNRIs. Unfortunately, up to 30% of patients can suffer from nausea due to Trintellix. The dose of Trintellix seems to have an impact, such that higher doses are associated with worsening nausea.
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Can Trintellix cause nausea?
Nausea is a well-known and well-described side effect of Trintellix (vortioxetine), especially when someone first starts taking this medication to manage their depression. The nausea is described as at its worst in the first week of therapy and can last up to 2 weeks before it begins to subside. Some, however, are afflicted for weeks after initiation. Nausea associated with Trintellix is also linked to dose, such that higher doses are associated with higher rates of nausea. In many analyses, the nausea caused by Trintellix is the most common side effect leading to withdrawal of the medication. If the side effect of nausea is too intense for a patient and they wish to stop it, they should only do so under the supervision of a medical professional, given the risk of discontinuation syndrome and withdrawal symptoms like anxiety, agitation, confusion, and irritability.
Why does Trintellix cause nausea?
Serotonin is a fundamental player in the gastrointestinal tract related to motility, nausea, and vomiting. In fact, almost 90-95% of the body’s serotonin is in the gut. The increased circulating serotonin from Trintellix and other antidepressants like Zoloft (sertraline), Lexapro (escitalopram), and Celexa (citalopram) stimulates the serotonin receptors throughout the gut, resulting in nausea. Other gastrointestinal side effects, like constipation or diarrhea, can also occur. Adaptation to the altered serotonin levels should occur after the first couple of weeks of therapy, and this common side effect of Trintellix should resolve over that period.
How to avoid nausea with Trintellix
Limiting nausea associated with Trintellix includes taking it with food, taking the medication at night so that the symptom of nausea is masked during sleeping, and starting with a lower dose. The nausea improves over time, usually resolving after about 2 weeks of therapy as the body adapts to the new serotonin levels. If nausea is really interfering with your daily activities, consider speaking with a healthcare professional about additional medications that you can take to help manage this side effect. Some typical antinausea medications, such as Zofran, can result in drug interactions, which can increase the risk of a life-threatening phenomenon known as serotonin syndrome. More homeopathic approaches, like ginger supplements to settle the stomach, may be a safer option. Initiation of any remedy—prescription or over-the-counter—should always be reviewed with a healthcare professional, as it may also interfere with other medications one may be taking.
Trintellix alternatives
Examples of other medications used to treat depression but with lower nausea risks include:
- Wellbutrin SR (bupropion)
- Remeron (mirtazapine)
- Cymbalta (duloxetine)
- Effexor XR (venlafaxine)
The reason the listed antidepressants generally cause less nausea is that their mechanisms of action are not as closely related to serotonin. Almost all serotonergic antidepressant drugs, however, will pose some increased risk of gastrointestinal side effects.
- Vortioxetine-induced nausea and its management, Psychiatry and Psychopharmacology (2017)
- Vortioxetine: a meta-analysis of 12 short-term, randomized, placebo-controlled clinical trials for the treatment of major depressive disorder, Journal of Psychiatry & Neuroscience (2014)
- Mechanisms of nausea and vomiting: current knowledge and recent advances in intracellular emetic signaling systems, International Journal of Molecular Sciences (2021)
- The safety and tolerability of vortioxetine: analysis of data from randomized placebo-controlled trials and open-label extension studies, Journal of Psychopharmacology (2016)