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

Summary

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).

Conditions

• Major Depressive Disorder

Interventions

DRUG

Vortioxetine

Antidepressant classified under the category "other antidepressants" according to the ATC/DDD index \[ATC=Anatomical Therapeutic Chemical Classification System; DDD=Defined Daily Dose\]. The dose will be flexible according to the clinical evaluation and in accordance with doses reported for elderly in the Summaries of Product Characteristics (available: https://farmaci.agenziafarmaco.gov.it/bancadatifarmaci/home) (namely: 5-20 mg/day).

DRUG

Sertraline

Antidepressant classified under the category "Selective serotonin reuptake inhibitors" according to the ATC/DDD index. The dose will be flexible according to the clinical evaluation and in accordance with doses reported for elderly in the Summaries of Product Characteristics (available: https://farmaci.agenziafarmaco.gov.it/bancadatifarmaci/home) (namely: 50-200 mg/day).

DRUG

citalopram

Antidepressant classified under the category "Selective serotonin reuptake inhibitors" according to the ATC/DDD index. The dose will be flexible according to the clinical evaluation and in accordance with doses reported for elderly in the Summaries of Product Characteristics (available: https://farmaci.agenziafarmaco.gov.it/bancadatifarmaci/home) (namely: 10-20 mg/day).

DRUG

Escitalopram

Antidepressant classified under the category "Selective serotonin reuptake inhibitors" according to the ATC/DDD index. The dose will be flexible according to the clinical evaluation and in accordance with doses reported for elderly in the Summaries of Product Characteristics (available: https://farmaci.agenziafarmaco.gov.it/bancadatifarmaci/home) (namely: 5-10 mg/day).

DRUG

Paroxetine

Antidepressant classified under the category "Selective serotonin reuptake inhibitors" according to the ATC/DDD index. The dose will be flexible according to the clinical evaluation and in accordance with doses reported for elderly in the Summaries of Product Characteristics (available: https://farmaci.agenziafarmaco.gov.it/bancadatifarmaci/home) (namely: 20-40 mg/day).

DRUG

Fluoxetine

Antidepressant classified under the category "Selective serotonin reuptake inhibitors" according to the ATC/DDD index. The dose will be flexible according to the clinical evaluation and in accordance with doses reported for elderly in the Summaries of Product Characteristics (available: https://farmaci.agenziafarmaco.gov.it/bancadatifarmaci/home) (namely: 20-60 mg/day).

DRUG

Fluvoxamine

Antidepressant classified under the category "Selective serotonin reuptake inhibitors" according to the ATC/DDD index. The dose will be flexible according to the clinical evaluation and in accordance with doses reported for elderly in the Summaries of Product Characteristics (available: https://farmaci.agenziafarmaco.gov.it/bancadatifarmaci/home) (namely: 100-300 mg/day).

Sponsors & Collaborators

• University of Catania

  collaborator OTHER

• Azienda Ospedaliera Universitaria Integrata Verona

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-02-01

Primary Completion

2023-02-28

Completion

2023-02-28

Countries

• Italy

Study Locations