Vortioxetine, sold under the brand names Trintellix (in the US) and Brintellix (in Europe) among others, is an antidepressant medication of the serotonin modulator and stimulator (SMS) class used in the treatment of major depressive disorder. Its effectiveness is viewed as similar to that of other antidepressants. It is taken orally. Common side effects include nausea, dry mouth, diarrhea, constipation, vomiting (3-6% of people), and sexual dysfunction. Serious side effects may include suicide in those under the age of 25, serotonin syndrome, bleeding, mania, and SIADH. A withdrawal syndrome may occur if the medication is abruptly stopped or the dose is decreased. Use during pregnancy and breastfeeding is not generally recommended. Vortioxetine's mechanism of action is not entirely understood, but is believed to be related to increasing serotonin levels and possibly interacting with certain serotonin receptors. It was approved for medical use in the United States and in the European Union in 2013. In 2020, it was the 243rd most commonly prescribed medication in the United States, with more than 1 million prescriptions.
Medical uses Vortioxetine is used as a treatment for major depressive disorder, with its effectiveness shown to be similar to other antidepressants and its effect size has been described as modest. Vortioxetine may be used when other treatments have failed. A 2017 Cochrane review on vortioxetine determined that its place in the treatment of severe depression is unclear due to low-quality evidence and that more studies comparing vortioxetine to selective serotonin reuptake inhibitors (SSRIs), the typical first-line treatments, are needed. Vortioxetine appears to work in depressed patients with anxiety. Vortioxetine is also used off label for anxiety. A 2016 review found it was not useful in generalized anxiety disorder at 2.5, 5.0, and 10 mg doses (15 and 20 mg doses were not tested). A 2019 meta-analysis found that vortioxetine did not produce statistically significant results over placebo in the symptoms, quality of life, and remission rates of generalized anxiety disorder, but it was well-tolerated. However, a 2018 meta-analysis supported use and efficacy of vortioxetine for generalized anxiety disorder, though stated that more research was necessary to strengthen the evidence. A 2021 systematic review and meta-analysis concluded that there was uncertainty about the effectiveness of vortioxetine for anxiety due to existing evidence being of very low-quality.
Contraindications Vortioxetine is contraindicated in those taking monoamine oxidase inhibitors (MAOIs), due to the possibility of serotonin syndrome.
Adverse effects
The most common side effects reported with vortioxetine are nausea, vomiting, constipation, and sexual dysfunction, among others. With the exceptions of nausea and sexual dysfunction, these side effects were reported by less than or equal to 10% of study participants given vortioxetine. Significant percentages of placebo-treated participants also report these side effects. Discontinuation of treatment due to adverse effects in clinical trials was 8% with vortioxetine versus 3% with placebo. Sexual dysfunction, such as decreased libido, abnormal orgasm, delayed ejaculation, and erectile dysfunction, are well-known side effects of SSRIs and serotonin–norepinephrine reuptake inhibitors (SNRIs). In clinical trials, sexual dysfunction occurred more often with vortioxetine than with placebo and appeared to be dose-dependent. Incidence of treatment-emergent sexual dysfunction as measured with the Arizona Sexual Experience Scale (ASEX) were 14 to 20% for placebo and 16 to 34% for vortioxetine over a dosage range of 5 to 20 mg/day. The incidence of sexual dysfunction with vortioxetine was similar to that with the SNRI duloxetine, which had an incidence of 26 to 28% at the used dosage of 60 mg/day. However, treatment-emergent sexual dysfunction caused by a prior SSRI was better improved by switching to vortioxetine than by switching to the SSRI escitalopram. In another study, vortioxetine at a dosage of 10 mg/day though not at 20 mg/day produced less sexual dysfunction than the SSRI paroxetine. These findings suggest that although vortioxetine can still cause sexual dysfunction itself, it may cause somewhat less sexual dysfunction than SSRIs and might be a useful alternative option for people experiencing sexual dysfunction with these medications. The rates of spontaneously reported sexual dysfunction are much lower than those obtained when researchers specifically ask subjects about sexual dysfunction (using the ASEX rating scale).
Based on preliminary clinical studies, vortioxetine may cause less emotional blunting than SSRIs and SNRIs. Vortioxetine used in combination with other serotonergic drugs such as MAOIs or SSRIs may result in serotonin syndrome.
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![Vortioxetine: Effectiveness of vortioxetine at 10, 15, and 20 mg/day versus placebo and duloxetine at 60 mg/day in the treatment of major depressive disorder in adults over 8 weeks (measured by improvement on the Montgomery–Åsberg Depression Rating Scale) in two randomized controlled trials.[35][36] Changes in MADRS total score from baseline at week 8 were –10.8 to –12.8 for placebo, –13.0 to –15.6 for vortioxetine, and –16.9 for duloxetine.[35][36]](https://upload.wikimedia.org/wikipedia/commons/thumb/b/b1/Effectiveness_of_vortioxetine_at_different_doses_versus_placebo_and_duloxetine_in_the_treatment_of_major_depressive_disorder_in_adults.png/1280px-Effectiveness_of_vortioxetine_at_different_doses_versus_placebo_and_duloxetine_in_the_treatment_of_major_depressive_disorder_in_adults.png?utm_source=en.wikipedia.org&utm_campaign=parser&utm_content=thumbnail)
![Vortioxetine: Vortioxetine levels after a single 10 mg oral dose of vortioxetine in 18 fasted and 18 fed healthy Japanese adults.[50]](https://upload.wikimedia.org/wikipedia/commons/thumb/1/18/Vortioxetine_levels_after_a_single_10_mg_oral_dose_of_vortioxetine_in_fasted_and_fed_healthy_Japanese_adults.png/1280px-Vortioxetine_levels_after_a_single_10_mg_oral_dose_of_vortioxetine_in_fasted_and_fed_healthy_Japanese_adults.png?utm_source=en.wikipedia.org&utm_campaign=parser&utm_content=thumbnail)
![Vortioxetine: Simulation of vortioxetine levels and accumulation with 10 mg/day oral vortioxetine plus a 17 mg intravenous bolus of vortioxetine versus 10 mg/day oral vortioxetine alone.[51]](https://upload.wikimedia.org/wikipedia/commons/thumb/1/13/Simulation_of_vortioxetine_accumulation_during_oral_vortioxetine_therapy_without_or_without_an_intravenous_bolus_of_vortioxetine.png/1280px-Simulation_of_vortioxetine_accumulation_during_oral_vortioxetine_therapy_without_or_without_an_intravenous_bolus_of_vortioxetine.png?utm_source=en.wikipedia.org&utm_campaign=parser&utm_content=thumbnail)
