Clinical trial NCT03779789: Vortioxetine in the Elderly vs. Selective Serotonin Reuptake Inhibitors (SSRIs): a Pragmatic Assessment
Official title: Assessing Tolerability and Efficacy of Vortioxetine Versus SSRIs in Elderly Patients With Depression: a Pragmatic, Multicenter, Open-label, Parallel-group, Superiority, Randomized Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Major Depressive Disorder
Keywords: vortioxetine
SSRI
depression
elderly
Lead sponsor: Azienda Ospedaliera Universitaria Integrata Verona
Sponsor class: OTHER
Collaborators: name: University of Catania
First posted: 2018-12-19
Enrollment: 362
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Pragmatic, multicenter, open-label, parallel-group, superiority, randomized trial.
Primary purpose: TREATMENT

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).


Eligibility criteria: 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).

Primary outcomes:
measure: Number of participants withdrawing from treatment due to adverse events (tolerability)
timeFrame: 6 months
Secondary outcomes:
measure: Number of participants withdrawing from treatment due to any cause (acceptability)
timeFrame: 6 months
measure: Overall mortality
timeFrame: 6 months
measure: Number of participants with at least one episode of self-harm
timeFrame: 6 months
measure: Number of participants died by suicide
timeFrame: 6 months
measure: Treatment-related adverse events as assessed by the ASEC
timeFrame: 6 months
measure: Number of participants with a reduction of at least 50% of the baseline score of the MADRS (responders)
timeFrame: 6 months
measure: Efficacy on depressive symptoms as assessed by the MADRS
timeFrame: 6 months
measure: Quality of life as assessed by the EQ-5D
timeFrame: 6 months
measure: Cognitive performance as assessed by the SBT
timeFrame: 6 months
Other outcomes:
Locations:
city: Catanzaro
country: Italy
facility: Azienda Ospedaliera Universitaria Mater Domini, Università Magna Grecia
city: Roma
country: Italy
facility: Sapienza Università di Roma, Dipartimento di Neurologia e Psichiatria
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Verona
Study officials:
References:
citation: 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.