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

NCT03779789 | Completed Phase 4 DMC

• 2 other identifiers: 2016-02349232018-001444-66
• Study Type: interventional
• Target: 362
• Locations: 1 country
• Sites: 3

Brief 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

Keywords

vortioxetine; SSRI; depression; elderly

Outcome Measures

Primary Outcomes (1)

• Number of participants withdrawing from treatment due to adverse events (tolerability)

  Participants withdrawing from allocated treatment due to adverse events on the number of randomized patients.

  6 months

Secondary Outcomes (9)

• Number of participants withdrawing from treatment due to any cause (acceptability)

  6 months

• Overall mortality

  6 months

• Number of participants with at least one episode of self-harm

  6 months

• Number of participants died by suicide

  6 months

• Treatment-related adverse events as assessed by the ASEC

  6 months

Study Arms (2)

vortioxetine

EXPERIMENTAL

Drug: Vortioxetine

SSRIs

ACTIVE COMPARATOR

Drug: Sertraline; Drug: citalopram; Drug: Escitalopram; Drug: Paroxetine; Drug: Fluoxetine; Drug: Fluvoxamine

Interventions

Vortioxetine DRUG

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).

Also known as: Brintellix, Trintellix

vortioxetine

Sertraline DRUG

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).

Also known as: Zoloft

SSRIs

citalopram DRUG

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).

Also known as: Elopram

SSRIs

Escitalopram DRUG

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).

Also known as: Entact

SSRIs

Paroxetine DRUG

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).

Also known as: Daparox

SSRIs

Fluoxetine DRUG

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).

Also known as: Prozac

SSRIs

Fluvoxamine DRUG

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).

SSRIs

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• years old or above;
• willing to participate by signing an informed consent;
• 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);
• treatment with an antidepressant is clinically appropriate, based on clinical/medical judgment;
• 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;
• uncertainty about which trial treatment would be best for the participant.

You may not qualify if:

• dementia, of any type and stage, as formally diagnosed by a specialist (geriatrician, neurologist, or others);
• diagnosis of schizophrenia or bipolar disorder;
• 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).

Sponsors & Collaborators

• Azienda Ospedaliera Universitaria Integrata Verona: lead
• University of Catania: collaborator

Study Sites (3)

Azienda Ospedaliera Universitaria Mater Domini, Università Magna Grecia

Catanzaro, Italy

Location

Sapienza Università di Roma, Dipartimento di Neurologia e Psichiatria

Roma, Italy

Location

Azienda Ospedaliera Universitaria Verona

Verona, 37134, Italy

Location

Related Publications (3)

• Ostuzzi G, Gastaldon C, Barbato A, D'Avanzo B, Tettamanti M, Monti I, Aguglia A, Aguglia E, Alessi MC, Amore M, Bartoli F, Biondi M, Bortolaso P, Callegari C, Carra G, Caruso R, Cavallotti S, Crocamo C, D'Agostino A, De Fazio P, Di Natale C, Giusti L, Grassi L, Martinotti G, Nose M, Papola D, Purgato M, Rodolico A, Roncone R, Tarsitani L, Turrini G, Zanini E, Amaddeo F, Ruggeri M, Barbui C. Tolerability and efficacy of vortioxetine versus SSRIs in elderly with major depression. Study protocol of the VESPA study: a pragmatic, multicentre, open-label, parallel-group, superiority, randomized trial. Trials. 2020 Aug 3;21(1):695. doi: 10.1186/s13063-020-04460-6.

  PMID: 32746941 RESULT

• Bartoli F, Cavaleri D, Riboldi I, Callovini T, Crocamo C, Gastaldon C, Aguglia A, Callegari C, Cavallotti S, Chiappini S, Cruciata M, D'Agostino A, Espa I, Grassi L, Ielmini M, Mammarella S, Martinotti G, Rania M, Rodolico A, Roncone R, Roselli V, Segura-Garcia C, Signorelli MS, Tarsitani L; VESPA Study Group; Ostuzzi G, Carra G. Efficacy and Tolerability of Vortioxetine Versus Selective Serotonin Reuptake Inhibitors for Late-Life Depression: A Post-hoc Analysis of the VESPA Study. Drugs Aging. 2025 Aug;42(8):771-780. doi: 10.1007/s40266-025-01231-3. Epub 2025 Jul 18.

  PMID: 40679716 DERIVED

• Ostuzzi G, Gastaldon C, Tettamanti M, Cartabia M, Monti I, Aguglia A, Aguglia E, Bartoli F, Callegari C, Canozzi A, Carbone EA, Carra G, Caruso R, Cavallotti S, Chiappini S, Colasante F, Compri B, D'Agostino A, De Fazio P, de Filippis R, Gari M, Ielmini M, Ingrosso G, Mammarella S, Martinotti G, Rodolico A, Roncone R, Sterzi E, Tarsitani L, Tiberto E, Todini L, Amaddeo F, D'Avanzo B; VESPA Study Group; Barbato A, Barbui C. 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. EClinicalMedicine. 2024 Feb 15;69:102491. doi: 10.1016/j.eclinm.2024.102491. eCollection 2024 Mar.

  PMID: 38384338 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Interventions

Vortioxetine; Sertraline; Citalopram; Escitalopram; Paroxetine; Fluoxetine; Fluvoxamine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; 1-Naphthylamine; Amines; Organic Chemicals; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Propylamines; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Piperidines; Oximes; Hydroxylamines

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Pragmatic, multicenter, open-label, parallel-group, superiority, randomized trial.

Study Record Dates

• First Submitted: December 12, 2018
• First Posted: December 19, 2018
• Study Start: February 1, 2019
• Primary Completion: February 28, 2023
• Study Completion: February 28, 2023
• Last Updated: May 19, 2023

Record last verified: 2023-05

Locations

IT (3)