# Efficacy and Tolerability of Vortioxetine Versus Selective Serotonin Reuptake Inhibitors for Late-Life Depression: A Post-hoc Analysis of the VESPA Study

## TL;DR

This study compared vortioxetine and SSRIs for treating depression in older adults and found no significant differences in effectiveness or side effects.

## Contribution

The study provides new evidence on the comparative efficacy and tolerability of vortioxetine versus SSRIs in late-life depression.

## Key findings

- No significant differences in MADRS improvement between vortioxetine and SSRIs at any follow-up.
- Vortioxetine did not show better response, remission, or discontinuation rates compared to SSRIs.
- Subgroup analysis confirmed similar outcomes when excluding drug discontinuers.

## Abstract

Usual treatment approaches for late-life depression primarily involve selective serotonin reuptake inhibitors (SSRIs). Recently, the potential role of vortioxetine has garnered attention. This study aimed to investigate whether vortioxetine is superior to SSRIs in terms of efficacy and tolerability in older people with moderate-to-severe depression.

The Vortioxetine in the Elderly versus SSRIs: a Pragmatic Assessment (VESPA) study was an assessor-blinded, randomized, parallel-group, superiority trial, comparing flexible doses of vortioxetine versus SSRIs in older adults with depression. This is a post-hoc analysis that excluded participants with milder symptoms of depression. The primary outcome was the change in Montgomery–Åsberg Depression Rating Scale (MADRS) scores. Secondary outcomes included clinical response (MADRS total score reduction of ≥ 50%), remission (a MADRS score < 10), and discontinuation rates. Clinical measures were conducted at baseline and at 1-month, 3-month, and 6-month (endpoint) visits.

In total, 302 individuals (mean age: 73.4 ± 5.9 years; 68.9% females), comprising 152 randomized to vortioxetine and 150 to SSRIs (sertraline N = 92; paroxetine N = 19; escitalopram N = 19; citalopram N = 16; fluoxetine N = 3; fluvoxamine N = 1), were included in this post-hoc analysis. No significant differences in MADRS improvement between vortioxetine and SSRIs were observed at any follow-up visits and 6-month endpoint (−11.8 ± 10.6 versus −14.0 ± 11.6; p = 0.12). This was further confirmed by a subgroup analysis excluding drug discontinuers (−16.8 ± 9.0 versus −17.6 ± 10.3; p = 0.51). In addition, people treated with vortioxetine did not exhibit better rates of response (44.1 versus 53.0%; p = 0.11), remission (25.7 versus 34.7%; p = 0.09), and discontinuation (38.0 versus 30.2%; p = 0.17), including discontinuation owing to either side effects or inefficacy, compared with those treated with SSRIs.

Vortioxetine was not superior to SSRIs in terms of efficacy and tolerability in older adults with moderate-to-severe depression. Additional trials, possibly based on fixed doses of vortioxetine, are needed.

Clinicaltrials.gov: NCT03779789, registered on 12 Dec 2018; EudraCT number: 2018-001444-66.

The online version contains supplementary material available at 10.1007/s40266-025-01231-3.