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Vortioxetine-induced nausea and its treatment: a case report

Calogero Crapanzano1, Andrea Politano2, Chiara Amendola3, Despoina Koukouna4, Ilaria Casolaro3

1 ASPAG, CSM Licata, Licata, Italy

2 Clinica S. Croce, Orselina, Switzerland

3 ASST Lariana, Como, Italy

4 U.O. Psichiatrica MANTOVA 1, MANTOVA, Italy


Received: 14/12/2019 – Accepted: 29/01/2020

DOI: 10.1590/0101-60830000000254

Vortioxetine is a multimodal antidepressant that binds with high affinity the serotonin transporter (SERT) > (serotonin receptor) 5-HT3 > 5-HT1A > 5-HT7 > 5-HT1B > 5-HT1D. It acts by inhibiting the SERT, with antagonism activity on the 5-HT1D, 5-HT7 and 5-HT3 receptors, partial agonism activity on the 5-HT1B receptor, agonism activity at 5HT1A receptor1. Vortioxetine is a compound approved by the FDA for major depressive disorder. Its efficacy and tolerability are widely proven2. Regarding tolerability, both in short and long-term studies, nausea was the most common treatment emergent adverse event (TEAE) and the primary TEAE that caused discontinuation after vortioxetine treatment2-4. Nausea is one of the most frequently reported adverse effects after SSRI and SNRI treatment. This can be attributed to their action on serotonin levels and on receptor 5-HT35. Nausea management includes: splitting daily dosage, taking medication after a meal, using drugs like 5-HT2 antagonists, proton pump inhibitors, promethazine, prochlorperazine, or ondansetron6. It is well established how the antidepressant tolerability influences quality of life and adherence to pharmacological treatment7. In this study we describe a case of nausea induced by vortioxetine along with its following treatment in a 32-year-old Italian patient with a diagnosis of bipolar disorder type 2, most recent depressive episode. At the time of our evaluation the patient was treated with lurasidone 37 mg/day and lithium carbonate 600 mg/day. In the past, trials with SSRIs and SNRIs have been conducted with improvement of depressive symptoms but the onset of sexual dysfunction led to drug discontinuation. A trial with bupropion was reported to have induced the onset of anxious symptoms. A trial was then started with vortioxetine 10 mg, increased to 20 mg after 8 days, then nausea occurred. It was decided to introduce mirtazapine 15 mg in the evening. After 2 days of mirtazapine augmentation the patient reported improvement in the nausea that was maintained at follow up; in addition, 2 weeks later an improvement in mood, anxiety, sleep regularity was observed, as well as the absence of sexual dysfunctions. In our case report we used mirtazapine in augmentation to vortioxetine following a pharmacodynamic and clinical reasoning. Mirtazapine, thanks to its 5-HT3 antagonism, has antiemetic properties already recognized in the literature8. Although the same 5-HT3 antagonism is universally accepted for vortioxetine as well, a recent study has shown a different behavior of vortioxetine on 5-HT3 receptors than that hypothesized so far: it can have, in fact, a significative agonist activity. Quoting: “[…] the mechanism of vortioxetine differs from classical 5-HT3A orthosteric ligands with inhibitory activity […] vortioxetine binding induces a brief agonistic response followed by a rapid transition into a desensitized state from which vortioxetine has an extremely slow unbinding rate”9. Our case report suggests the possible role of mirtazapine against antidepressant-induced nausea. Further studies are needed to investigate how these data could be useful to explain and manipulate the clinical effects in terms of efficacy and tolerability.

Conflict of interests

The authors declare no conflict of interest.


The research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.


1. D’Agostino A, English CD, Rey JA. Vortioxetine (brintellix): a new serotonergic antidepressant. P T. 2015;40(1):36-40.

2. Pae CU, Wang SM, Han C, Lee SJ, Patkar AA, Masand PS, et al. Vortio- xetine: a meta-analysis of 12 short-term, randomized, placebo-controlled clinical trials for the treatment of major depressive disorder. J Psychiatry Neurosci. 2015;40(3):174-86.

3. Nomikos GG, Tomori D, Zhong W, Affinito J, Palo W. Efficacy, safety, and tolerability of vortioxetine for the treatment of major depressive disorder in patients aged 55 years or older. CNS Spectr. 2017;22(4):348-62.

4. Inoue T, Nishimura A, Sasai K, Kitagawa T. Randomized, 8-week, doubleblind, placebo-controlled trial of vortioxetine in Japanese adults with major depressive disorder, followed by a 52-week open-label extension trial. Psychiatry Clin Neurosci. 2018;72(2):103-15.

5. Carvalho AF, Sharma MS, Brunoni AR, Vieta E, Fava GA. The Safety, Tolerability and Risks Associated with the Use of Newer Generation Antidepressant Drugs: A Critical Review of the Literature. Psychother Psychosom. 2016;85(5):270-88.

6. Kelly K, Posternak M, Alpert JE. Toward achieving optimal response: understanding and managing antidepressant side effects. Dialogues Clin Neurosci. 2008;10(4):409-18.

7. Cleare A, Pariante CM, Young AH, Anderson IM, Christmas D, Cowen PJ, et al. Evidence-based guidelines for treating depressive disorders with antidepressants: A revision of the 2008 British Association for Psychopharmacology guidelines. J Psychopharmacol. 2015;29:459-525.

8. Kim SW, Shin IS, Kim JM, Kim YC, Kim KS, Kim KM, et al. Effectiveness of mirtazapine for nausea and insomnia in cancer patients with depres- sion. Psychiatry Clin Neurosci. 2008;62(1):75-83.

9. Ladefoged LK, Munro L, Pedersen AJ, Lummis SCR, Bang-Andersen B, Balle T, et al. Modeling and Mutational Analysis of the Binding Mode for the Multimodal Antidepressant Drug Vortioxetine to the Human 5-HT3A Receptor. Mol Pharmacol. 2018;94(6):1421-34.