Abstract
IntroductionDepression 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 analysisThis 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 disseminationThis 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 registrationClinicaltrials.gov: NCT03779789, Registered on 19 December 2018. Submitted on 19 December. EudraCT number: 2018–001444-66.Trial statusProtocol 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.
Highlights
Depression is a highly prevalent condition in the elderly, with a vast impact on quality of life, life expectancy, and medical outcomes
The only available trial conducted in the older people demonstrated that vortioxetine was more effective than placebo in terms of response, i.e. participants with > = 50% reduction in the Hamilton Depression Scale-24 total score in 8 weeks (301 participants, relative risk 1.49, 95% CI 1.14 to 1.95), while no differences emerged in terms of tolerability [32]
This study is designed to achieve a high level of pragmatism. This approach will allow us to minimize the risk of selection bias, to resemble routine clinical procedures as much as possible and to maximize the external validity and generalizability of the results [34]
Summary
Depression is a highly prevalent condition in the elderly, with a vast impact on quality of life, life expectancy, and medical outcomes. Older people may be vulnerable to adverse events due to frailties associated with the ageing process [10], medical comorbidities, multiple treatments and high risk of pharmacological interactions [11, 12]. SSRIs are not without risks in older people; in particular, hyponatraemia, postural hypotension, falls, gastrointestinal bleeding and sexual dysfunctions are the most common side effects [15, 16] Other antidepressants, such as tricyclic antidepressants (TCAs), serotonin and norepinephrine reuptake inhibitors (SNRIs) and mirtazapine are associated with a similar or higher risk of a number of adverse events, including sedation, confusion, urinary retention and cardiovascular and gastrointestinal issues [16], and are generally avoided in these patients. The magnitude of beneficial effects of antidepressants in latelife depression has been questioned [17], making it hard for clinicians to accurately balance benefits and risks
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