New hope for Hard-to-Treat depression in seniors: esketamine spray vs aripiprazole
NCT ID NCT07153406
First seen Jun 26, 2026 · Last updated Jun 26, 2026
Summary
This study compares two add-on treatments—esketamine nasal spray and aripiprazole pills—for older adults (60-74) whose depression hasn't improved with standard antidepressants. Around 220 participants will receive either esketamine once or twice weekly or daily aripiprazole, alongside their current medication. The goal is to see which approach better reduces depressive symptoms and is safer over 32 weeks.
What this could mean
Our plain-language read of the trial. This is informational only, not medical advice or a prediction.
- Active substance
- Esketamine nasal spray (flexible doses 28-84 mg) and oral aripiprazole (5-30 mg daily)
- What this could lead to
- If esketamine works better than aripiprazole, it could offer a new, fast-acting option for older adults with hard-to-treat depression.
- What could go wrong
- This is an early-phase 3 trial with no results yet. Esketamine may cause side effects like dizziness or dissociation, and the benefit over existing treatments is not guaranteed.
This is an AI summary of the original study and may miss details. Read our disclaimer.
Study facts
What this study's own registry entry says, in plain language.
- Phase
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Phase 3
Large-scale testing in a bigger group. Usually the last step before a treatment can be approved.
- Participants
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About 220 people
The number the study aims to enrol. It can still change while the study runs.
- Expected to start
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Sep 2025
An estimate. Start dates often move.
- Expected to finish
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Jan 2029
An estimate. End dates often move.
- Lead sponsor
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Other sponsor
The registry's catch-all category, for sponsors it does not file as a company, a government agency, or a research network.
Who can take part
This study's own entry requirements. Only the study team can say for certain whether you qualify.
- Ages
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60 to 74 years
- Sex
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Anyone
- Healthy volunteers
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Not accepted
This study is not open to healthy volunteers. The entry requirements below say who it is open to.
Show the full entry requirements Hide the full entry requirements
Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.
Inclusion Criteria: * Patients between 60-74 years * To be receiving antidepressant treatment that includes an antidepressant at the time of screening that is not responding (less than 25% improvement in symptoms) after receiving an adequate dose \[or local equivalent, if applicable\] for at least 6 weeks and have been increased to the dose maximum allowed * Current antidepressant treatment must have been immediately preceded by failure to respond to at least 3, but not more than 5, different consecutive treatments (all within the same moderately severe depressive episode) with antidepressant drugs (AD) taken at an appropriate dose for at least least 6 weeks (3 antidepressant failures including the current one) * To have been treated with at least 3 different classes of antidepressants between treatments taken at appropriate doses for at least 6 weeks without response in the current moderate to severe depressive episode (including current treatment with an antidepressant) * To be taking a single oral antidepressant on day 1 before randomization * Participants who, at the time of screening, are taking a combination of antidepressants and/or rescue treatment (other than aripiprazole) for the current moderate to severe depressive episode may participate in the study. Exclusion Criteria: * Treatment with drugs contraindicated with the use of esketamine and aripiprazole. * Patients in whom a high risk of suicide is detected at the screening visit, according to the criteria established by Columbia University according to the C-SSRS evaluation * Patients who are participating in another clinical trial with active treatment * Patients who do not have the capacity to consent to participation in the trial or who do not have a representative to confirm their participation * Hypersensitivity to any of the active ingredients of any of the branches of treatment, or to any of the excipients of its pharmaceutical form * Patients in whom increased blood pressure or blood pressure intracranial fluid poses a serious risk
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Conditions
The condition(s) this trial relates to.
As listed by the trial registrant
The condition terms exactly as the trial's registrant entered them.
How to take part
Only the study team decides who joins. These are the ways to reach them.
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The places running it
9 sites. The list below names each one and where it is.
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The official record
ClinicalTrials.gov lists the study team's own contact details, including names and phone numbers. We don't republish those.
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A doctor treating you
A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.
Contacts and locations
Locations
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Centro Sociosanitario Hermanas Hospitalarias de Palencia
Palencia, 34004, Spain
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Clínica Psiquiátrica Padre Menni
Pamplona, Navarre, 31014, Spain
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Corporacion Sanitaria Parc Tauli
Sabadell, 08208, Spain
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Hospital Benito Menni y Fidmag Hermanas Hospitalarias
Barcelona, 08830, Spain
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Hospital De La Santa Creu i Sant Pau
Barcelona, 08041, Spain
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Hospital Mare de Déu de La Mercè
Barcelona, 08042, Spain
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Hospital Sagrat Cor. Martorell
Barcelona, 08760, Spain
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Hospital Universitario Virgen del Rocio
Seville, 41013, Spain
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Hospital Vall d'Hebron
Barcelona, 08014, Spain
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