BackgroundMajor depressive disorders represent a significant burden to society, and it is recommended that antidepressant therapy should last at least 6 months. In Italy, antidepressant use in clinical practice was reported to increase by 1.7% in 2020 compared to 2019, but only 40% of new prescriptions are characterized by a treatment duration longer than 3 months.ObjectiveThe study aims to describe adherence and persistence to therapy in a subset of antidepressants (citalopram, duloxetine, escitalopram, paroxetine, sertraline, venlafaxine) vs. vortioxetine in Italy during a 2-year period from 2017 to 2019.MethodsA retrospective analysis of the longitudinal patient database reporting data from general practitioners on drug prescriptions in Italy was carried out in a cohort of 8,235 adult patients who were prescribed antidepressants.ResultsOverall, 32.4% of the patients adhered to treatment for ≥6 months over a 1-year period. Vortioxetine had a lower risk of low adherence compared to duloxetine, paroxetine, and venlafaxine and a higher risk compared to citalopram, escitalopram, and sertraline. 68.7% of patients discontinued treatment during follow-up. The greatest percentage of patients continuing therapy was seen with duloxetine, while citalopram was associated with the highest proportion of patients discontinuing therapy. No significant differences in discontinuation were observed when comparing vortioxetine to the other antidepressants.ConclusionAdherence results were considerably less than the 6-month recommendation in this real-world analysis of antidepressant therapies. Also, persistence to therapy was low, with most patients discontinuing treatment. Thus, there is a need for interventions to help patients adhere to their planned therapy.