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

Assessing Tolerability and Efficacy of Vortioxetine Versus SSRIs in Elderly Patients With Depression: a Pragmatic, Multicenter, Open-label, Parallel-group, Superiority, Randomized Trial

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).

Inclusion Criteria:

1. 65 years old or above;
2. willing to participate by signing an informed consent;
3. suffering from an episode of major depression, based on clinical judgment (guided by DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) criteria);
4. treatment with an antidepressant is clinically appropriate, based on clinical/medical judgment;
5. agreement between investigator and patient to discontinue any current antidepressant, second generation antipsychotic, or lithium. According to the pragmatic design of the study, the discontinuation will be performed according to common routine practice. No specific protocols for discontinuation will be applied. All other concomitant medications are allowed;
6. uncertainty about which trial treatment would be best for the participant.

Exclusion Criteria:

1. dementia, of any type and stage, as formally diagnosed by a specialist (geriatrician, neurologist, or others);
2. diagnosis of schizophrenia or bipolar disorder;
3. clinical conditions or treatments which contraindicate the use of oral vortioxetine or SSRIs, according to clinical/medical judgment (for example conditions or treatments at high risk of bleeding, convulsions, serotoninergic syndrome, hyponatraemia, etc.). All concomitant medications will be prescribed according to routine clinical practice, in compliance with the synthesis of the product characteristics (Riassunto delle Caratteristiche del Prodotto - RCP) registered in the databank of the AIFA (Agenzia Italiana del Farmaco) (available at https://farmaci.agenziafarmaco.gov.it/bancadatifarmaci/cerca-farmaco).