Vortioxetine (Trintellix) Patient Guide: Benefits, Dosing, and Side Effects Explained

This guide is adapted from the clinician guide authored by Sebastián Malleza, M.D., M.Sc. at the Psychopharmacology Institute. For the complete clinical resource, visit: Vortioxetine Guide: Pharmacology, Indications, Dosing Guidelines and Adverse Effects

What is Vortioxetine?

Vortioxetine (brand name Trintellix, formerly called Brintellix) is a medication approved for treating major depressive disorder (MDD)[1]. It works differently from many other antidepressants because it affects multiple brain systems involving serotonin, a chemical messenger important for mood regulation[2].

Compared to other antidepressants, Trintellix may offer these advantages:

• May help with cognitive symptoms of depression (problems with thinking, concentration, and memory)[11,12,13]
• Lower risk of sexual side effects compared to other antidepressants[21,23,25]
• Minimal withdrawal symptoms when stopping the medication (due to its 66-hour half-life)[20,21,22]
• Few drug interactions (except with certain medications discussed below)[3,7]

Your doctor might recommend alternatives if you:

• Are sensitive to stomach upset (Trintellix commonly causes nausea)[3]
• Need treatment primarily for anxiety disorders (insufficient evidence for anxiety disorders)[14,15]
• Have concerns about medication cost (Trintellix is newer and may be more expensive)
• Take certain medications that interact with Trintellix[3,7]

How Does This Medication Work?

Vortioxetine works through two main mechanisms[1,2]:

1. Serotonin reuptake inhibition: Like many antidepressants, it increases serotonin levels in the brain by preventing its reabsorption.
2. Direct effects on serotonin receptors: Unlike most antidepressants, it also directly affects several different types of serotonin receptors in the brain:

• Acts as an agonist (activator) at the 5-HT1A receptor
• Acts as a partial agonist at the 5-HT1B receptor
• Acts as an antagonist (blocker) at the 5-HT1D, 5-HT3, and 5-HT7 receptors

This “multimodal” action may contribute to its effects on both mood and cognition[2,5].

How to Take This Medication

Vortioxetine comes as film-coated tablets in 5 mg, 10 mg, and 20 mg strengths[3].

Typical Dosing:

• Starting dose: Usually 10 mg once daily[3]
  • Your doctor may start you at 5 mg once daily if you experience nausea or don’t tolerate higher doses
• Target dose: 20 mg once daily[3]
• Maximum dose:
• General population: 20 mg daily[3]
  • For certain people who process medications differently (poor CYP2D6 metabolizers), the maximum is 10 mg daily[3]

Important instructions:

• Swallow the tablet whole
• Take it at approximately the same time each day
• Can be taken in the morning or evening
• Taking with food may help reduce nausea
• If you miss a dose, take it as soon as you remember. If it’s almost time for your next dose, skip the missed dose and continue with your regular schedule. Do not take two doses to make up for a missed one

Common Side Effects

Many side effects improve over time as your body adjusts to the medication.

Digestive system effects:

• Nausea (occurs in 21-32% of people)[3]
• Most common side effect
• Usually starts within the first week, often after 1-2 days of treatment
• Often improves with continued treatment
• Can be minimized by taking with food
• Approximately 10% still experience nausea at treatment end with doses 10-20mg/day
• Diarrhea (7-10% incidence)[3]
• Dry mouth (7% incidence)[3]
• Constipation (3-6% incidence)[3]
• Vomiting (3-6% incidence)[3]

Other common side effects:

• Dizziness (6-9% incidence)[3]
• Abnormal dreams (2-3% incidence)[3]
• Itching/pruritus (2-3% incidence)[3]

Advantages over other antidepressants:

• Sexual function: Lower rates of sexual dysfunction compared to many other antidepressants[21,23,25]
• May improve sexual function in patients switching from high-risk antidepressants (e.g., citalopram, paroxetine, or sertraline)[23]
• Discontinuation symptoms: Lower risk compared to other antidepressants due to vortioxetine’s 66-hour half-life[20,21,22]

Important Safety Information

Do Not Take Vortioxetine If:

• You are taking or have recently taken (within 14 days) medications called MAOIs (monoamine oxidase inhibitors)[3]

Talk to Your Doctor Before Taking Vortioxetine If You:

• Take other medications that affect serotonin (other antidepressants, triptans, tramadol, St. John’s Wort)[3]
• Take medications that affect CYP2D6 (bupropion, fluoxetine, paroxetine, quinidine)[3,7]
• Take medications like rifampin, carbamazepine, or phenytoin[7]
• Have bleeding problems or take blood thinners[28]
• Are pregnant, planning pregnancy, or breastfeeding[3,33,34]
• Are elderly or take diuretics (increased risk of low sodium)[29,31]
• Have very high body weight (BMI ≥35)[36]

Avoid While Taking Vortioxetine:

• Other medications that increase serotonin levels without talking to your doctor first
• Driving or operating machinery until you know how this medication affects you

When to Contact Your Doctor Immediately

Contact your healthcare provider right away if you experience:

• Unusual changes in behavior, thoughts of suicide, or worsening depression
• Signs of serotonin syndrome: agitation, hallucinations, rapid heart rate, fever, excessive sweating, shivering, muscle stiffness or twitching, trouble with coordination, nausea, vomiting, or diarrhea[3,26]
• Unusual bleeding or bruising[27,28]
• Signs of low sodium: headache, difficulty concentrating, memory problems, confusion, weakness, unsteadiness[29,30,31,32]
• Severe nausea or vomiting that doesn’t improve
• Any concerning or severe side effects

Starting and Stopping the Medication

Starting: It may take several weeks before you notice the full benefits of this medication.

Stopping: Do not stop taking vortioxetine suddenly without talking to your doctor. For 15-20mg/day doses, a reduction to 10mg/day for one week before discontinuation is recommended[3,21,22].

Possible discontinuation symptoms include:

• Dizziness
• Nausea
• Headache
• Irritability
• Mood swings
• Insomnia

Special Considerations

Pregnancy and Breastfeeding

• Limited information is available about the safety of vortioxetine during pregnancy[3,33]
• The medication passes into breast milk in small amounts. Talk to your doctor about the risks and benefits if you are breastfeeding[3,34]

Older Adults

• No dose adjustment officially recommended, but your doctor may start you at a lower dose (5 mg/day)[3,35]
• Your doctor will monitor you more closely for side effects like low sodium levels[3,35]

Kidney and Liver Problems

• No dose adjustment needed for liver or kidney problems[3]

Overweight Patients

• The medication may stay in your system longer[36]
• May need longer washout periods when switching to certain other medications[36]

References

1. Köhler, S., Cierpinsky, K., Kronenberg, G., & Adli, M. (2016). The serotonergic system in the neurobiology of depression: Relevance for novel antidepressants. Journal of Psychopharmacology, 30(1), 13–22.
2. Sowa-Kućma, M., et al. (2017). Vortioxetine: A review of the pharmacology and clinical profile of the novel antidepressant. Pharmacological Reports, 69(4), 595–601.
3. Trintellix FDA Prescribing Information.
4. Celada, P., Bortolozzi, A., & Artigas, F. (2013). Serotonin 5-HT1A Receptors as Targets for Agents to Treat Psychiatric Disorders: Rationale and Current Status of Research. CNS Drugs, 27(9), 703–716.
5. Sanchez, C., Asin, K. E., & Artigas, F. (2015). Vortioxetine, a novel antidepressant with multimodal activity: Review of preclinical and clinical data. Pharmacology & Therapeutics, 145, 43–57.
6. Pehrson, A. L., et al. (2013). Lu AA21004, a novel multimodal antidepressant, produces regionally selective increases of multiple neurotransmitters–a rat microdialysis and electrophysiology study. European Neuropsychopharmacology, 23(2), 133–145.
7. Chen, G., Højer, A.-M., Areberg, J., & Nomikos, G. (2018). Vortioxetine: Clinical Pharmacokinetics and Drug Interactions. Clinical Pharmacokinetics, 57(6), 673–686.
8. Lam, R. W., et al. (2024). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2023 Update on Clinical Guidelines for Management of Major Depressive Disorder in Adults. Can. J. Psychiatry, 69(9), 641–687.
9. Qaseem, A., et al. (2023). Nonpharmacologic and Pharmacologic Treatments of Adults in the Acute Phase of Major Depressive Disorder: A Living Clinical Guideline From the American College of Physicians. Annals of Internal Medicine, 176(2), 239–252.
10. Cipriani, A., et al. (2018). Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: A systematic review and network meta-analysis. Lancet, 391(10128), 1357–1366.
11. Lenze, E. J., et al. (2020). Augmenting Computerized Cognitive Training With Vortioxetine for Age-Related Cognitive Decline: A Randomized Controlled Trial. American Journal of Psychiatry, 177(6), 548–555.
12. Huang, I.-C., et al. (2022). Effect of Vortioxetine on Cognitive Impairment in Patients With Major Depressive Disorder: A Systematic Review and Meta-analysis of Randomized Controlled Trials. International Journal of Neuropsychopharmacology, 25(12), 969–978.
13. Blumberg, M. J., Vaccarino, S. R., & McInerney, S. J. (2020). Procognitive Effects of Antidepressants and Other Therapeutic Agents in Major Depressive Disorder: A Systematic Review. The Journal of Clinical Psychiatry, 81(4).
14. Bandelow, B., et al. (2023). World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for treatment of anxiety, obsessive-compulsive and posttraumatic stress disorders – Version 3. Part I: Anxiety disorders. World J. Biol. Psychiatry, 24(2), 79–117.
15. Qin, B., et al. (2019). Vortioxetine treatment for generalised anxiety disorder: A meta-analysis of anxiety, quality of life and safety outcomes. BMJ Open, 9(11), e033161.
16. Pizarro, M., et al. (2014). An updated review of antidepressants with marked serotonergic effects in obsessive–compulsive disorder. Expert Opinion on Pharmacotherapy, 15(10), 1391–1401.
17. Santayana, G. P. de, et al. (2017). Vortioxetine Efficiency in Controlling Obsessive Symptoms in Patients with Depression. A Case Report. European Psychiatry, 41(S1), S715–S715.
18. Jiménez-Fernández, B., et al. (2024). Use of vortioxetine in treating obsessive-compulsive disorder: A case report. European Psychiatry, 67(S1), S632–S632.
19. De Berardis, D., et al. (2017). Vortioxetine and Aripiprazole Combination in Treatment-Resistant Obsessive-Compulsive Disorder: A Case Report. Journal of Clinical Psychopharmacology, 37(6), 732.
20. Areberg, J., et al. (2014). Population Pharmacokinetic Meta-Analysis of Vortioxetine in Healthy Individuals. Basic & Clinical Pharmacology & Toxicology, 115(6), 552–559.
21. Baldwin, D. S., et al. (2016). The safety and tolerability of vortioxetine: Analysis of data from randomized placebo-controlled trials and open-label extension studies. Journal of Psychopharmacology, 30(3), 242–252.
22. Siwek, M., et al. (2021). Withdrawal Symptoms Following Discontinuation of Vortioxetine—Retrospective Chart Review. Pharmaceuticals, 14(5), 451.
23. Jacobsen, P. L., et al. (2015). Effect of Vortioxetine vs. Escitalopram on Sexual Functioning in Adults with Well-Treated Major Depressive Disorder Experiencing SSRI-Induced Sexual Dysfunction. The Journal of Sexual Medicine, 12(10), 2036–2048.
24. de Boer, M. K., & Schoevers, R. A. (2017). Methodological differences as an explanation for the divergent results of studies on sexual dysfunction related to the use of vortioxetine. Journal of Psychopharmacology, 31(3), 389–390.
25. Jacobsen, P. L., et al. (2016). Treatment-emergent sexual dysfunction in randomized trials of vortioxetine for major depressive disorder or generalized anxiety disorder: A pooled analysis. CNS Spectrums, 21(5), 367–378.
26. Ong, C. Y., & Vasanwala, F. F. (2018). Diaphoresis: A Presentation of Serotonin Syndrome From Vortioxetine. The Primary Care Companion for CNS Disorders, 20(3), 26849.
27. Chen, G., Zhang, W., & Serenko, M. (2015). Lack of effect of multiple doses of vortioxetine on the pharmacokinetics and pharmacodynamics of aspirin and warfarin. The Journal of Clinical Pharmacology, 55(6), 671–679.
28. Rahman, A. A., et al. (2024). Concomitant Use of Selective Serotonin Reuptake Inhibitors With Oral Anticoagulants and Risk of Major Bleeding. JAMA Network Open, 7(3), e243208.
29. Gheysens, T., Van Den Eede, F., & De Picker, L. (2024). The risk of antidepressant-induced hyponatremia: A meta-analysis of antidepressant classes and compounds. European Psychiatry, 67(1), e20.
30. D’Agostino, A., English, C. D., & Rey, J. A. (2015). Vortioxetine (Brintellix): A New Serotonergic Antidepressant. Pharmacy and Therapeutics, 40(1), 36–40.
31. Pelayo-Terán, J. M., Martínez-Pérez, M. M., & Zapico-Merayo, Y. (2017). Safety in the use of antidepressants: Vortioxetine-induce hyponatremia in a case report. Revista De Psiquiatria Y Salud Mental, 10(4), 219–220.
32. Sasaki, T., et al. (2024). Vortioxetine‐induced syndrome of inappropriate secretion of antidiuretic hormone: A case report. Neuropsychopharmacology Reports, 44(2), 479–481.
33. Shweiki, S., & Diav-Citrin, O. (2021). Pregnancy outcome after first trimester exposure to vortioxetine: A case series. Birth Defects Research, 113(6), 511–515.
34. Marshall, K., et al. (2021). Transfer of the Serotonin Modulator Vortioxetine into Human Milk: A Case Series. Breastfeeding Medicine, 16(10), 843–845.
35. Trintellix Canada Prescribing Information.
36. Greenblatt, D. J., Harmatz, J. S., & Chow, C. R. (2018). Vortioxetine Disposition in Obesity: Potential Implications for Patient Safety. Journal of Clinical Psychopharmacology, 38(3), 172–179.

Disclaimer: This information is not a substitute for professional medical advice. Always consult with your healthcare provider regarding your specific medical condition and treatment options.