Long-term effectiveness and tolerability of vortioxetine in a naturalistic outpatient sample

Background

Vortioxetine is a multimodal antidepressant that combines serotonin reuptake inhibition with direct modulation of multiple serotonergic receptors, including 5-HT1A agonism, 5-HT1B partial agonism, and antagonism at 5-HT3 and 5-HT7 receptors [1]. The drug has been approved by both the FDA and the EMA for the treatment of Major Depressive Disorder at standard doses of 10–20 mg/day [2]. Beyond its antidepressant efficacy, vortioxetine has demonstrated pro-cognitive and anxiolytic properties, which are particularly relevant in real-world clinical settings where patients frequently present with complex symptom profiles, including cognitive dysfunction and comorbid anxiety disorders [3].

Methods

This study is an observational, longitudinal investigation conducted in a naturalistic clinical setting at the Department of Mental Health and Addiction of ASST Fatebenefratelli-Sacco, Milan. A total of 33 adult outpatients treated with vortioxetine were included. The prescribed dosage ranged from 20 to 30 mg/day, reflecting routine clinical practice rather than controlled trial conditions. Data were collected at three timepoints: baseline (T0), approximately 6 months (T1), and approximately 24 months (T2). Variables assessed included sociodemographic characteristics, primary psychiatric diagnosis according to DSM-5 criteria, and clinical severity rated using the Clinical Global Impression scale (CGI, scores 1–4). Additional data included therapeutic strategy (first-line treatment, switch from a previous antidepressant, or add-on therapy), vortioxetine dosage, adverse events, psychiatric and medical comorbidities, concomitant pharmacological treatments, and the presence of concurrent psychotherapy. The longitudinal design allowed for the evaluation of both tolerability and clinical patterns over an extended follow-up period.

Results

The sample had a mean age of 51.0 ± 14.5 years, with a slight female predominance (55%). The majority of patients were diagnosed with Major Depressive Disorder (64%), while the remaining participants presented with other psychiatric conditions. The most frequent therapeutic strategy was switching from a previous antidepressant (52%), followed by first-line prescription (24%) and add-on use (21%), indicating a heterogeneous and clinically complex population. The most commonly prescribed dose was 20 mg/day, used in 69% of patients, with a mean dosage of 20.1 ± 3.8 mg/day and a range between 20 and 30 mg/day. Tolerability outcomes were favorable: adverse events decreased substantially over time, from 45% at baseline to 9% at 24 months, corresponding to an 80% reduction, and no serious adverse events were reported. Statistical analyses revealed a significant positive correlation between the number of prior depressive episodes and the number of concomitant psychiatric medications (r = 0.659, p = 0.014), suggesting greater treatment complexity in more recurrent cases. Additionally, male patients showed significantly higher rates of psychiatric comorbidity compared to females (0.73 vs 0.28, p = 0.019).

Conclusions

Vortioxetine, administered at doses of 20–30 mg/day, demonstrated excellent long-term tolerability in a real-world population. Its multimodal mechanism of action supports its clinical utility in patients with depression, particularly in the presence of comorbid anxiety and cognitive symptoms. The observed reduction in adverse events over time further reinforces its favorable safety profile. However, given the limitations of the small sample size and observational design, future studies with larger cohorts, randomized controlled methodologies are needed to confirm and extend these findings.

References

1. Sanchez, C., Asin, K. E., & Artigas, F., 2015. Vortioxetine, a novel antidepressant with multimodal activity: Review of preclinical and clinical data. Pharmacology & Therapeutics, 145, 43-57. https://doi.org/10.1016/j.pharmthera.2014.07.001
2. Thase, M. E., Mahableshwarkar, A. R., Dragheim, M., Loft, H., & Vieta, E., 2016. A meta-analysis of randomized, placebo-controlled trials of vortioxetine for the treatment of major depressive disorder in adults. European Neuropsychopharmacology, 26(6), 979-993. https://doi.org/10.1016/j.euroneuro.2016.03.007
3. McIntyre, R. S., Lophaven, S., & Olsen, C. K., 2014. A randomized, double-blind, placebo-controlled study of vortioxetine on cognitive function in depressed adults. International Journal of Neuropsychopharmacology, 17(10), 1557-1567. https://doi.org/10.1017/S1461145714000546