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. 2024 Feb 15:69:102491.
doi: 10.1016/j.eclinm.2024.102491. eCollection 2024 Mar.

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

Giovanni Ostuzzi  1 , Chiara Gastaldon  1   2 , Mauro Tettamanti  3 , Massimo Cartabia  3 , Igor Monti  3 , Andrea Aguglia  4   5 , Eugenio Aguglia  6 , Francesco Bartoli  7 , Camilla Callegari  8 , Andrea Canozzi  1 , Elvira Anna Carbone  9   10   11 , Giuseppe Carrà  7 , Rosangela Caruso  12   13 , Simone Cavallotti  14   15 , Stefania Chiappini  16 , Fabrizio Colasante  1   17 , Beatrice Compri  1 , Armando D'Agostino  14   15 , Pasquale De Fazio  9   10   11 , Renato de Filippis  9   10   11 , Matteo Gari  5 , Marta Ielmini  8 , Gianmarco Ingrosso  14   15 , Silvia Mammarella  18 , Giovanni Martinotti  16 , Alessandro Rodolico  6 , Rita Roncone  18 , Enrico Sterzi  19 , Lorenzo Tarsitani  20 , Elisa Tiberto  12   13 , Liliana Todini  20 , Francesco Amaddeo  1 , Barbara D'Avanzo  3 ; VESPA Study Group; Angelo Barbato  3 , Corrado Barbui  1
Collaborators, Affiliations

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

Giovanni Ostuzzi et al. EClinicalMedicine. .

Abstract

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".

Keywords: Adverse events; Major depressive disorder; Older adults; Serotonin selective reuptake inhibitors; Tolerability; Vortioxetine.

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Conflict of interest statement

A. A. received honoraria for presentations from Lundbeck, Viatris, Angelini. E. A. received research grants, consulting fees and honoraria for presentations from Allergan, Angelini, Doc Generici, FB-Health, Janssen-Cilag, Lundbeck, Otsuka, Fidia, Recordati. E. A. C. received support for attending meetings from Janssen-Cilag. F. B. received consulting fees and support for attending meetings from Angelini, Janssen-Cilag, Otsuka. G.M. received research grants, consulting fees and honoraria for presentations from Angelini, Doc Generici, Janssen-Cilag, Lundbeck, Neuraxpharm, Otsuka, Pfizer, Servier, Rovi, Recordati. R. d. F. received consulting fees and honoraria for presentations from Janssen-Cilag, and support for attending meetings from Janssen-Cilag and ROVI. All the other authors have no competing interests to disclose.

Figures

Fig. 1
Fig. 1
Study flow-chart.
Fig. 2
Fig. 2
Time to discontinuation due to adverse events. A) Shows the worst-case scenario, where missing data for the primary outcome were assumed to be discontinuations due to adverse events. B) Shows the best-case scenario, where missing data for the primary outcome were assumed to be participants continuing treatment. Legend: SSRI, selective serotonin reuptake inhibitor.
See this image and copyright information in PMC

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