Tolerability and efficacy of vortioxetine versus SSRIs in elderly with major depression. Study protocol of the VESPA study: a pragmatic, multicentre, open-label, parallel-group, superiority, randomized trial
Authors: Ostuzzi Giovanni , Gastaldon Chiara , Barbato Angelo , D’Avanzo Barbara , Tettamanti Mauro , Monti Igor , Aguglia Andrea , Aguglia Eugenio , Alessi Maria Chiara , Amore Mario , Bartoli Francesco , Biondi Massimo , Bortolaso Paola , Callegari Camilla , Carrà Giuseppe , Caruso Rosangela , Cavallotti Simone , Crocamo Cristina , D’Agostino Armando , De Fazio Pasquale , Di Natale Chiara , Giusti Laura , Grassi Luigi , Martinotti Giovanni , Nosé Michela , Papola Davide , Purgato Marianna , Rodolico Alessandro , Roncone Rita , Tarsitani Lorenzo , Turrini Giulia , Zanini Elisa , Amaddeo Francesco , Ruggeri Mirella , Barbui Corrado 
Published: August 2020

Abstract
Introduction
Depression is a highly prevalent condition in the elderly, with a vast impact on quality of life, life expectancy, and medical outcomes. Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed agents in this condition and, although generally safe, tolerability issues cannot be overlooked. Vortioxetine is an antidepressant with a novel mechanism of action. Based on studies to date, it may have a promising tolerability profile in the elderly, as it does not adversely affect psychomotor or cognitive performance and does not alter cardiovascular and endocrine parameters. The present study aims to assess the tolerability profile of vortioxetine in comparison with the SSRIs considered as a single group in elderly participants with depression. The rate of participants withdrawing from treatment due to adverse events after 6 months of follow up will be the primary outcome.

Methods and analysis
This is a pragmatic, multicentre, open-label, parallel-group, superiority, randomized trial funded by the Italian Medicines Agency (AIFA - Agenzia Italiana del Farmaco). Thirteen Italian Community Psychiatric Services will consecutively enrol elderly participants suffering from an episode of major depression over a period of 12 months. Participants will be assessed at baseline and after 1, 3 and 6 months of follow up. At each time point, the following validated rating scales will be administered: Montgomery–Åsberg Depression Rating Scale (MADRS), Antidepressant Side-Effect Checklist (ASEC), EuroQual 5 Dimensions (EQ-5D), Short Blessed Test (SBT), and Charlson Age-Comorbidity Index (CACI). Outcome assessors and the statistician will be masked to treatment allocation. A total of 358 participants (179 in each group) will be enrolled.

Ethics and dissemination
This study will fully adhere to the ICH E6 Guideline for Good Clinical Practice. Participants’ data will be managed and safeguarded according to the European Data Protection Regulation 2016/679. An external Ethical Advisory Board will help guarantee high ethical standards.

Trial registration
Clinicaltrials.gov: NCT03779789, Registered on 19 December 2018. Submitted on 19 December. EudraCT number: 2018–001444-66.

Trial status
Protocol version 1.5; 09/06/2018. Recruitment started In February 2019 and it is ongoing. It is expected to end approximately on 30 September 2021.