Ostuzzi Giovanni, Gastaldon Chiara, Tettamanti Mauro, Cartabia Massimo, Monti Igor, Aguglia Andrea, Aguglia Eugenio, Bartoli Francesco, Callegari Camilla, Canozzi Andrea, Carbone Elvira Anna, Carrà Giuseppe, Caruso Rosangela, Cavallotti Simone, Chiappini Stefania, Colasante Fabrizio, Compri Beatrice, D'Agostino Armando, De Fazio Pasquale, de Filippis Renato, Gari Matteo, Ielmini Marta, Ingrosso Gianmarco, Mammarella Silvia, Martinotti Giovanni, Rodolico Alessandro, Roncone Rita, Sterzi Enrico, Tarsitani Lorenzo, Tiberto Elisa, Todini Liliana, Amaddeo Francesco, D'Avanzo Barbara, Barbato Angelo, Barbui Corrado
Department of Neuroscience, Biomedicine and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy.
Institute for Social and Preventive Medicine, University of Bern, Bern, Switzerland.
EClinicalMedicine. 2024 Feb 15;69:102491. doi: 10.1016/j.eclinm.2024.102491. eCollection 2024 Mar.
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.
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).
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.
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.
The study was funded by the Italian Medicines Agency within the "2016 Call for Independent Drug Research".
重度抑郁症（MDD）在老年人中普遍存在且会导致残疾。鉴于其耐受性，伏硫西汀在这类脆弱人群中可能是选择性5-羟色胺再摄取抑制剂（SSRI）的一个有前景的替代药物。
我们开展了一项随机、评估者和统计学家双盲的优效性试验，纳入患有MDD的老年人。该研究于2019年2月2日至2023年2月22日在11个意大利精神科服务机构进行。参与者被随机分配至伏硫西汀或根据常规做法选择的一种SSRI。六个月后因不良事件导致的治疗中断是主要结局，我们旨在检测出有利于伏硫西汀的12%的差异。该研究已在在线资料库clinicaltrials.gov（NCT03779789）注册。
意向性分析人群包括179名被随机分配至伏硫西汀组和178名被随机分配至SSRI组的个体。平均年龄为73.7岁（标准差6.1），264名参与者（69%）为女性。在伏硫西汀组中，78人（44%）在六个月时因不良事件中断治疗，而在SSRI组中这一比例为59人（33%）（比值比1.56；95%置信区间1.01 - 2.39）。校正分析和符合方案分析证实了有利于SSRI的点估计值，但无显著差异。除未校正的生存分析显示SSRI优于伏硫西汀外，次要结局的结果表明两组之间在安全性和耐受性方面没有实质性差异。总体而言，在缓解率、抑郁症状和生活质量方面未出现显著差异，而在认知表现方面SSRI优于伏硫西汀。
与之前的假设相反，在本研究中，伏硫西汀在患有MDD的老年人中并未显示出比SSRI更好的耐受性。此外，伏硫西汀在与抑郁相关的认知症状方面的假设优势可能受到质疑。该研究的统计效力和高度实用的设计使其结果可推广至实际临床实践。
该研究由意大利药品管理局在“2016年独立药物研究征集”项目中资助。
