Up to 40% of patients with depression do not respond to first-line treatment and among those who do respond, only about half achieve remission. For this reason, guidelines for treating depression mainly focus on how to proceed in cases of treatment failure or only partial response. The aim of this review paper is to present studies evaluating the effectiveness of vortioxetine in treatment of patients with depression following treatment failure with an SSRI/SNRI drug. Vortioxetine is an effective antidepressant that, after treatment failure with an SSRI/SNRI drug, allows 32–55% of patients to achieve remission. However, the assessed dosing regimen of vortioxetine deviated from that used in the initial therapy of depression, i.e. by the second week (8th day) of therapy the dose was increased to the maximum – 20 mg/day and the period for treatment effectiveness assessment was 8–12 weeks. This dosing regimen more closely resembles the pharmacological approach utilised in the treatment of obsessive-compulsive disorder rather than depression. The administration of a high dose of vortioxetine did not negatively impact the tolerability of the treatment, even among patient groups at high risk of adverse events (elderly patients, co-existence of anxiety). The most common adverse effect was nausea; however, it was not observed that rapid dose escalation intensified this effect. This is most likely attributable to the receptor profile of vortioxetine.