학술논문
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 trialResearch in context
Document Type
article
Author
Giovanni Ostuzzi; Chiara Gastaldon; Mauro Tettamanti; Massimo Cartabia; Igor Monti; Andrea Aguglia; Eugenio Aguglia; Francesco Bartoli; Camilla Callegari; Andrea Canozzi; Elvira Anna Carbone; Giuseppe Carrà; Rosangela Caruso; Simone Cavallotti; Stefania Chiappini; Fabrizio Colasante; Beatrice Compri; Armando D'Agostino; Pasquale De Fazio; Renato de Filippis; Matteo Gari; Marta Ielmini; Gianmarco Ingrosso; Silvia Mammarella; Giovanni Martinotti; Alessandro Rodolico; Rita Roncone; Enrico Sterzi; Lorenzo Tarsitani; Elisa Tiberto; Liliana Todini; Francesco Amaddeo; Barbara D'Avanzo; Angelo Barbato; Corrado Barbui; Maria Chiara Alessi; Gabriele Avincola; Bianca Bachi; Gianna Bernasconi; Andrea Birgillito; Emanuele Bisso; Stefano Bonora; Angela Calabrese; Tommaso Callovini; Aurelia Canestro; Salvo Canonico; Chiara Alessandro Capogrosso; Elvira Carbone; Doriana Carosielli; Ivano Caselli; Daniele Cavaleri; Clara Cavallotto; Marco Cesca; Cecilia Chiarenza; Riccardo Matteo Cioni; Sara Coloccini; Marco Cruciata; Claudia Cumerlato; Renato De Filippis; Manuela De Palma; Sasha Del Vecchio; Bianca Della Rocca; Chiara Di Natale; Ettore D'Onofrio; Irene Espa; Giulia Fior; Marta Gancitano; Barbara Giordano; Laura Giusti; Luigi Grassi; Pierluca Guzzi; Celeste Isella; Annamaria Lax; Leonardo Marano; Federico Marconi; Marco Marella; Alessia Metelli; Giulia Michencig; Andrea Miuli; Alessandro Moncada; Pietro Morello; Federico Moretti; Marco Morreale; Alessio Mosca; Christian Nasti; Michela Nosé; Filippo Ogheri; Margherita Oresti; Alessandra Ornaghi; Dario Palpella; Corinna Pancheri; Davide Papola; Silvia Passeri; Mauro Pettorusso; Susanna Piacenti; Irene Pinucci; Valentina Pugliese; Marianna Purgato; Marianna Rania; Federica Robbi; Samantha Romito; Barbara Ronchi; Valentina Roselli; Cristina Segura-Garcia; Maria Salvina Signorelli; Gabriele Simonelli; Antonella Sociali; Serena Sturiale; Antonio Tambelli; Beatrice Todesco; Alice Trabucco; Giulia Turrini; Veronica Villa; Federico Wiedenmann; Luca Zambuto; Elisa Zanini; Chiara Zannini; Luigi Zerbinati
Source
EClinicalMedicine, Vol 69, Iss , Pp 102491- (2024)
Subject
Language
English
ISSN
2589-5370
Abstract
Summary: Background: Major depressive disorder (MDD) is prevalent and disabling among older adults. Standing on its tolerability profile, vortioxetine might be a promising alternative to selective serotonin reuptake inhibitors (SSRIs) in such a vulnerable population. Methods: We conducted a randomised, assessor- and statistician-blinded, superiority trial including older adults with MDD. The study was conducted between 02/02/2019 and 02/22/2023 in 11 Italian Psychiatric Services. Participants were randomised to vortioxetine or one of the SSRIs, selected according to common practice. Treatment discontinuation due to adverse events after six months was the primary outcome, for which we aimed to detect a 12% difference in favour of vortioxetine. The study was registered in the online repository clinicaltrials.gov (NCT03779789). Findings: The intention-to-treat population included 179 individuals randomised to vortioxetine and 178 to SSRIs. Mean age was 73.7 years (standard deviation 6.1), and 264 participants (69%) were female. Of those on vortioxetine, 78 (44%) discontinued the treatment due to adverse events at six months, compared to 59 (33%) of those on SSRIs (odds ratio 1.56; 95% confidence interval 1.01–2.39). Adjusted and per-protocol analyses confirmed point estimates in favour of SSRIs, but without a significant difference. With the exception of the unadjusted survival analysis showing SSRIs to outperform vortioxetine, secondary outcomes provided results consistent with a lack of substantial safety and tolerability differences between the two arms. Overall, no significant differences emerged in terms of response rates, depressive symptoms and quality of life, while SSRIs outperformed vortioxetine in terms of cognitive performance. Interpretation: As opposed to what was previously hypothesised, vortioxetine did not show a better tolerability profile compared to SSRIs in older adults with MDD in this study. Additionally, hypothetical advantages of vortioxetine on depression-related cognitive symptoms might be questioned. The study's statistical power and highly pragmatic design allow for generalisability to real-world practice. Funding: The study was funded by the Italian Medicines Agency within the “2016 Call for Independent Drug Research”.