Can talk therapy keep Esketamine's relief going?
NCT ID NCT04760652
First seen Sep 16, 2026 · Last updated Sep 17, 2026 · Updated 1 time
Summary
Researchers at Yale University are testing whether adding cognitive behavioral therapy (CBT) after esketamine treatment helps prevent relapse in people with major depression and suicidal thoughts. All participants receive esketamine, then half are randomly assigned to also get computer-assisted CBT while the other half receive their usual care. The study primarily checks whether a larger trial like this is feasible, and also looks at suicide risk and depression symptoms over time.
What this could mean
Our plain-language read of the trial. This is informational only, not medical advice or a prediction.
- Active substance
- cognitive behavioral therapy added after esketamine treatment
- What this could lead to
- If it works, this could offer a way to help people stay well after esketamine lifts severe depression and suicidal thoughts, by adding talk therapy to their care.
- What could go wrong
- This is a small feasibility study, so it may not show whether the combination truly prevents relapse. Esketamine itself can cause side effects like dissociation and blood pressure changes, and not everyone responds to it.
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Study facts
What this study's own registry entry says, in plain language.
- Phase
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Not a phased trial
Phase numbers describe drug development. The registry uses this when they do not apply, as it does for trials of devices, procedures or behaviour changes, and for observational studies.
- Participants
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93 people
The number who actually took part.
- Started
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Mar 2021
- Finished
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Jun 2025
- 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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18 to 65 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: * Participants are eligible for the study if they meet all the following criteria: 1. Written informed consent before any study procedures are performed 2. Meeting criteria for inpatient admission for suicidal ideation or attempt at one of the study sites 3. Recommended by a physician for esketamine treatment 4. Males or females ages 18 through 65 years of age 5. Diagnosis of major depressive disorder as confirmed by the MINI (inpatient) or the HAM-D-17 (outpatient) 6. Willing to adhere to a reliable form of contraception throughout the trial and for one month following completion of the trial (for subjects who are sexually active) 7. In the opinion of the investigator, the patient is willing and able to comply with scheduled visits, treatment plan, and other trial procedures for the duration of the study Exclusion Criteria: * Participants are excluded if they meet any of the following criteria: 1. Active substance use disorder (except tobacco) within 6 months of screening date 2. Meets DSM-5 criteria for bipolar disorder, schizophrenia, schizophreniform disorder, schizoaffective disorder, or pervasive development disorder 3. Dementia or other cognitive disorder or intellectual disability that would impair the subject's ability to meaningfully engage in CBT (per investigator judgment) 4. Any other medical or psychiatric comorbidity that the investigator judges would put the participant at additional undue risk due to study participation or would impair subject's ability to participate in the study. 5. Current or planned participation in a formal CBT program defined by the following characteristics, each session has an agenda, a homework assignment is given at each session, and the homework assignment from the previous session is reviewed at the following appointment. 6. Previous Esketamine or ketamine treatment that did not produce a clinical response as outlined below. * 6 treatments with Esketamine at a dose of 56 mg or more with no clinical response * 6 treatments of IV ketamine at a dose between 0.4 mg/kg and 0.7mg /kg with no clinical response Patients must not have received Esketamine or ketamine treatment within the past 12 weeks of time of enrollment. 7. The patient is pregnant or breastfeeding 8. Unable to give informed consent 9. Was previously enrolled/randomized into the trial 10. Patients who have a contraindication to receiving Esketamine including any of the following: * aneurysmal vascular disease * arteriovenous malformation * history of intracerebral hemorrhage * hypersensitivity to esketamine or ketamine
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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.
Contacts and locations
Locations
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Emory University
Atlanta, Georgia, 30329, United States
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UAB Medicine | Heersink School of Medicine
Birmingham, Alabama, 35294, United States
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Yale University
New Haven, Connecticut, 06511, United States
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