VORTIOXETINE VERSUS SSRIs FOR THE TREATMENT OF DEPRESSION IN THE ELDERLY: A PRAGMATIC RANDOMIZED CLINICAL TRIAL

Background. Depression is among the leading causes of disability in older adults. In the elderly, selective serotonin reuptake inhibitors (SSRIs) are considered effective and generally safer compared to other classes of antidepressants, such as tricyclics. Nevertheless, older people are particularly vulnerable to adverse events. Vortioxetine is a novel antidepressant, licenced for depression in 2013. Existing data on vortioxetine suggest that it should not negatively affect cognitive performance and electrocardiogram parameters. It showed to be effective compared to placebo and as effective as SNRIs. To our knowledge randomized controlled trials comparing vortioxetine to SSRIs, the current usual care for depressed elderly, are lacking. Objectives. The study assessed if, under real-world clinical circumstances, vortioxetine is better tolerated as compared with the SSRIs in elderly participants with depression. Methods. We conducted a randomized, parallel-group, multicentre, open-label, pragmatic, superiority trial funded by the Italian Medicines Agency (AIFA - Agenzia Italiana del Farmaco). Twelve Italian Community Psychiatric Services consecutively enrolled elderly participants suffering from an episode of major depression over a period of 12 months. Participants were assessed at baseline and after 1, 3 and 6 months of follow-up. The primary outcome was the rate of participants withdrawing from treatment due to adverse events after six months of follow-up. At each time point, the following secondary outcomes were assessed: effectiveness, quality of life, cognitive performance, comorbidities and side effects. Outcome assessors and the statistician were masked to treatment allocation. EudraCT number: 2018-001444-66; Clinicaltrials.gov: NCT03779789. The present thesis is an interim analysis of the partial sample collected till October 2020. Results. During 2019 and the first nine months of 2020 we screened 90 inpatients, of which 67 met the inclusion criteria, gave written consent and were consequently randomized to vortioxetine or SSRIs (37 and 30 respectively. By the end of 2020, the study should have included 358 participants, however the first and second pandemic waves have not allowed to recruit participants as planned, and therefore recruitment is still ongoing. This analysis is based on the first 67 enrolled participants. At endpoint three participants in the vortioxetine group discontinued medication due to AEs versus 7 in the SSRIs group (9.09 vs. 24.14%), a difference that is not statistically significant (p = 0.17). At one month, discontinuation rates due to AEs were significantly different, being higher in patients receiving SSRIs than vortioxetine (20.67 vs 3.03%, p value= 0.04), with an odds ratio (OR) of 8.09 (95% confidence interval ZZ to ZZ). There were no differences in the secondary outcomes between the two groups of interventions. Discussion. This innovative study will provide head-to-head comparisons for well-established antidepressant treatment options in elderly patients with depression. The preliminary analysis presented here is extremely promising, as it suggests a potentially beneficial effect of vortioxetine over the SSRIs in terms of tolerability profile. However, the pandemic period has significantly decreased the recruitment rate, making the present findings unpowered to provide firm conclusions. For this reason, recruitment is still ongoing, aiming to reach the target sample size by the end of 2021. To our knowledge this is the first study that directly compared vortioxetine with SSRIs. The results of this study will be easily generalizable, thanks to its highly pragmatic nature.