Vortioxetine in the Elderly vs. Selective Serotonin Reuptake Inhibitors (SSRIs): a Pragmatic Assessment

Summary

Background. Depression is a highly frequent condition in the elderly, with a huge impact on quality of life, life expectancy, and medical outcomes. SSRIs are commonly prescribed in elderly depressed patients and, although generally safe, they may be associated with tolerability issues. Based on available studies, vortioxetine is likely to have a promising tolerability profile in the elderly, as it does not adversely affect psychomotor or cognitive performance, wakefulness, body weight, and electrocardiogram parameters. Objectives. Assessing the comparative tolerability, safety and efficacy of vortioxetine compared with the SSRIs as a group (including sertraline, citalopram, escitalopram, paroxetine, fluoxetine, fluvoxamine) in elderly patients affected by major depression. The primary outcome will be the withdrawal rate due to adverse events. Methods. This is a pragmatic, multicenter, open-label, parallel-group, superiority, randomized trial. Twelve Italian Community Psychiatric Services will consecutively enrol elderly patients suffering from an episode of major depression who get in contact over a period of 12 months. By employing the web-based application RedCap, doctors will be able to randomize patients to vortioxetine or one of the SSRIs, chosen on the basis of clinical judgment, and to collect basic socio-demographic and clinical data. Trained and blinded assessors will administer five validated rating scales: Montgomery-Åsberg Depression Rating Scale (MADRS), Antidepressant Side-Effect Checklist (ASEC), EuroQual 5 Dimensions (EQ-5D), Charlson Age-Comorbidity Index (CACI), and Short Blessed Test (SBT). Patients will be assessed after 1, 3 and 6 months. Expected results. On the basis of current literature, the investigators hypothesize vortioxetine to be superior to SSRIs as a group in terms of tolerability. As vortioxetine is expected to reduce the withdrawal rates due to adverse events of about 12% compared to SSRIs, and assuming that about 23% of the participants could be lost within 6 months, the investigators aim to enrol 358 patients (179 in each group).

Timeline

Start

2019-02-01

Primary completion

2023-02-28

Completion

2023-02-28

Publications

• Results Ostuzzi G, Gastaldon C, Barbato A, D'Avanzo B, Tettamanti M, Monti I, Aguglia A, Aguglia E, Alessi MC, Amore M, Bartoli F, Biondi M, Bortolaso P, Callegari C, Carra G, Caruso R, Cavallotti S, Crocamo C, D'Agostino A, De Fazio P, Di Natale C, Giusti L, Grassi L, Martinotti G, Nose M, Papola D, Purgato M, Rodolico A, Roncone R, Tarsitani L, Turrini G, Zanini E, Amaddeo F, Ruggeri M, Barbui C. 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. Trials. 2020 Aug 3;21(1):695. doi: 10.1186/s13063-020-04460-6.
• Bartoli F, Cavaleri D, Riboldi I, Callovini T, Crocamo C, Gastaldon C, Aguglia A, Callegari C, Cavallotti S, Chiappini S, Cruciata M, D'Agostino A, Espa I, Grassi L, Ielmini M, Mammarella S, Martinotti G, Rania M, Rodolico A, Roncone R, Roselli V, Segura-Garcia C, Signorelli MS, Tarsitani L; VESPA Study Group; Ostuzzi G, Carra G. Efficacy and Tolerability of Vortioxetine Versus Selective Serotonin Reuptake Inhibitors for Late-Life Depression: A Post-hoc Analysis of the VESPA Study. Drugs Aging. 2025 Aug;42(8):771-780. doi: 10.1007/s40266-025-01231-3. Epub 2025 Jul 18.
• Ostuzzi G, Gastaldon C, Tettamanti M, Cartabia M, Monti I, Aguglia A, Aguglia E, Bartoli F, Callegari C, Canozzi A, Carbone EA, Carra G, Caruso R, Cavallotti S, Chiappini S, Colasante F, Compri B, D'Agostino A, De Fazio P, de Filippis R, Gari M, Ielmini M, Ingrosso G, Mammarella S, Martinotti G, Rodolico A, Roncone R, Sterzi E, Tarsitani L, Tiberto E, Todini L, Amaddeo F, D'Avanzo B; VESPA Study Group; Barbato A, Barbui C. Tolerability of vortioxetine compared to selective serotonin reuptake inhibitors in older adults with major depressive disorder (VESPA): a randomised, assessor-blinded and statistician-blinded, multicentre, superiority trial. EClinicalMedicine. 2024 Feb 15;69:102491. doi: 10.1016/j.eclinm.2024.102491. eCollection 2024 Mar.

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