Vortioxetine, sold under the brand name Trintellix (in the US) and Brintellix (in the EU) among others, is an antidepressant medication of the serotonin modulator and stimulator (SMS) class used in the treatment of major depressive disorder.

[15] Common side effects include nausea, dry mouth, diarrhea, constipation, vomiting (3-6% of people), and sexual dysfunction.

[15][11] Serious side effects may include suicide in those under the age of 25, serotonin syndrome, bleeding, mania, and SIADH.

[32] 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.

[33] 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.

[34] 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.

[36] Vortioxetine is contraindicated in those taking monoamine oxidase inhibitors (MAOIs), due to the possibility of serotonin syndrome.

[11] The most common side effects reported with vortioxetine are nausea, vomiting, constipation, and sexual dysfunction, among others.

[11] 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.

[11][39] Discontinuation of treatment due to adverse effects in clinical trials was 8% with vortioxetine versus 3% with placebo.

[17][18][11] Based on preliminary clinical studies, vortioxetine may cause less emotional blunting than SSRIs and SNRIs.

[13] The incidence of side effects with vortioxetine, like nausea, headache, vomiting, and insomnia, was correspondingly increased with the combination.

[13] Similar influences on vortioxetine pharmacokinetics may also occur with other strong cytochrome P450 inducers like carbamazepine and phenytoin.

[11] The risk of serotonin syndrome may also be increased when vortioxetine is combined with other serotonergic drugs, like SSRIs, SNRIs, tricyclic antidepressants (TCAs), triptans, tramadol, tryptophan, buspirone, St John's wort, fentanyl, and lithium, among others.

[13][46][49] This is in apparent contrast to SSRIs and SNRIs, which appear to require a minimum of 70 to 80% occupancy for antidepressant efficacy.

[18][46] In relation to the preceding, the contribution of serotonin receptor interactions to the antidepressant effects of vortioxetine is unknown and remains to be established.

[13][11][18][17] Uncertainties remain about whether vortioxetine is indeed a clinically multimodal antidepressant or whether it is effectively "[just] another selective serotonin reuptake inhibitor".

[46][14] Whether or not the 5-HT3 receptor antagonism of vortioxetine likewise does this in humans or contributes to its clinical antidepressant efficacy is unclear.

[13] The accumulation index of vortioxetine (area-under-the-curve levels after a single dose versus at steady state) is 5 to 6.

[13] A loading dose given intravenously has been found to achieve steady-state levels more rapidly with oral vortioxetine therapy.

[39] The acid dissociation constant (pKa) values for vortioxetine hydrobromide were determined to be 9.1 (± 0.1) and 3.0 (± 0.2) according to an Australian Public Assessment Report.

[53] Vortioxetine was invented by scientists at Lundbeck who reported the rationale and synthesis for the drug (then called Lu AA21004) in a 2011 paper.

[61] There is also interest in vortioxetine for the potential treatment of social phobia,[62] neuropathic pain,[63] and for cognitive enhancement in major depression.