A 2017 Cochrane review on vortioxetine determined that the place for it in the treatment of severe depression is unclear due to low-quality evidence and that more study is needed comparing vortioxetine to selective serotonin reuptake inhibitors (SSRIs) which are typical first-line treatments.Vortioxetine is also used off-label for anxiety. A 2016 review found it was not useful in generalized anxiety disorder at 2.5, 5, and 10 mg doses (15 and 20 mg doses were not tested). A 2019 meta-analysis found that vortioxetine didnt 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 very low-quality. In a 2020 network meta-analysis of randomized controlled trials, vortioxetine was associated with among the lowest remission rates for generalized anxiety disorder of the included medications (odds ratio = 1.30 for vortioxetine, range of odds ratios for other agents = 1.13–2.70). Dosage
The recommended starting dosage of vortioxetine is 10 mg/day. The dosage should then be increased as tolerated to 20 mg/day. For individuals who dont tolerate higher doses, 5 mg/day may be considered. The maximum recommended dose of vortioxetine in known CYP2D6 poor metabolizers is 10 mg/day.
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 Johns wort, fentanyl, and lithium, among others. However, vortioxetine is not considered to be contraindicated with serotonergic medications besides MAOIs. Pharmacology
Pharmacodynamics
Vortioxetine increases serotonin concentrations in the brain by inhibiting its reuptake in the synapse, and also modulates (activates or blocks) certain serotonin receptors. This puts it in the class of serotonin modulators and stimulators, which also includes vilazodone. More specifically, vortioxetine is a serotonin reuptake inhibitor, agonist of the serotonin 5-HT1A receptor, partial agonist of the 5-HT1B receptor, and antagonist of the serotonin 5-HT1D, 5-HT3, and 5-HT7 receptors, as well as an apparent ligand of the β1-adrenergic receptor. In terms of functional activity however, vortioxetine appears to be much more potent on serotonin reuptake inhibition and 5-HT3 receptor antagonism than for its interactions with the other serotonin receptors. Whereas vortioxetine has IC50 or EC50 values of 5.4 nM for the SERT and 12 nM for the 5-HT3 receptor, its values are 120 to 450 nM for the 5-HT1A, 5-HT1B, 5-HT1D, and 5-HT7 receptors. This translates to about 22- to 83-fold selectivity for SERT inhibition and 10- to 38-fold selectivity for 5-HT3 antagonism over activities at the other serotonin receptors.It has been claimed that the serotonin transporter (SERT) and 5-HT3 receptor may be primarily occupied at lower clinical doses of vortioxetine and that the 5-HT1B, 5-HT1A, and 5-HT7 receptors may additionally be occupied at higher doses.