Depression and SuicideENDURENCT04760652
Cognitive Behavioral Therapy Following Esketamine for Major Depression and Suicidal Ideation for Relapse Prevention
A study testing Cognitive Behavioral Therapy CBT and TAU in people with Depression and Suicide, run by Yale University at 3 sites in United States.
Trial summary
This is a rater-blinded, randomized controlled trial. All patients will receive esketamine for treatment of Major Depression with Suicidal Ideation (MDSI). Subjects will be randomized (1:1) to receive CBT (computer-assisted) or TAU alone following esketamine. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Depression and Suicide
- What is being tested?
- Cognitive Behavioral Therapy CBT and TAU
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 93 participants
- Where
- 3 sitesUnited States
- Study dates
- 5 Mar 2021to 30 Jun 2025
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants are eligible for the study if they meet all the following criteria:
- Written informed consent before any study procedures are performed
- Meeting criteria for inpatient admission for suicidal ideation or attempt at one of the study sites
- Recommended by a physician for esketamine treatment
- Males or females ages 18 through 65 years of age
- Diagnosis of major depressive disorder as confirmed by the MINI (inpatient) or the HAM-D-17 (outpatient)
- 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)
- 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
Who cannot join
- Participants are excluded if they meet any of the following criteria:
- Active substance use disorder (except tobacco) within 6 months of screening date
- Meets DSM-5 criteria for bipolar disorder, schizophrenia, schizophreniform disorder, schizoaffective disorder, or pervasive development disorder
- Dementia or other cognitive disorder or intellectual disability that would impair the subject's ability to meaningfully engage in CBT (per investigator judgment)
- 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.
- 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.
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- 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.
- The patient is pregnant or breastfeeding
- Unable to give informed consent
- Was previously enrolled/randomized into the trial
- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Emory University
Atlanta, Georgia, 30329
UAB Medicine | Heersink School of Medicine
Birmingham, Alabama, 35294
Yale University
New Haven, Connecticut, 06511
About this study
Official title: CBT-ENDURE: Cognitive Behavioral Therapy Following Esketamine for Major Depression and Suicidal Ideation for Relapse Prevention
This is a rater-blinded, randomized controlled trial. All patients will receive esketamine for treatment of Major Depression with Suicidal Ideation (MDSI). Subjects will be randomized (1:1) to receive CBT (computer-assisted) or TAU alone following esketamine.
Read the detailed description
Specific Aim 1: To determine the feasibility and safety of performing a larger study examining the effectiveness and mechanism of action of CBT to improve the longer-term outcomes following esketamine treatment in patients hospitalized for suicidal ideation or suicide attempt.
Specific Aim 2: To evaluate the appropriateness and utility of the proposed tests of cognitive control measures in exploring the mechanisms underlying the effects on depression of esketamine and the combination of esketamine+CBT.
Specific Aim 3: To examine the efficacy of esketamine+CBT combination compared to esketamine+TAU in reducing suicidal ideation.
In August 2022, the targeted enrollment was expanded to include outpatient participants, the anticipated enrollment was increased from 60 to 100 participants as a result.
- Conditions
- Depression and Suicide
- Being tested
- Cognitive Behavioral Therapy CBT, TAU
- Keywords
- Depression, Suicide
- Medical subject headings
- Depression, Suicide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cognitive Behavioral Therapy CBTBehavioural
CBT: In-person and computer-based components (Good Days Ahead) First 4 weeks of CBT are twice weekly; thereafter weekly CBT
TAUOther
Treatment as usual- can vary.
| Study group | Role | What they receive |
|---|---|---|
| CBT Cognitive Behavioral Therapy | Active comparator | Participants will receive CBT, which will consist of in-person and computer-based component (based on Good Days Ahead). This will consist of 20 sessions given over 16 weeks. Receives: Behavioral: Cognitive Behavioral Therapy CBT |
| TAU Treatment As Usual | Other | Participants will undergo Treatment as usual (TAU). These patients will undergo standard, post-hospitalization clinical treatments, which many include physician visits and psychotherapy (except for formal CBT). Receives: Other: TAU |
What is being measured
The primary outcome is the main question the study is designed to answer.
To Determine the Feasibility of Performing a Larger Study With Similar Design by Measuring of Recruitment Rates.
Feasibility will be evaluated by measures of recruitment rates measured by attaining 80% of recruitment target will be considered feasible. Presented are those that were consented and then randomized.
Measured: Recruitment rates will be assessed at 18 months.
To Determine the Feasibility of Performing a Larger Study With Similar Design by Measuring Attrition.
Feasibility will be evaluated by measures of attrition rates by attaining 80% of retention will of 70% of participants will be considered feasible.
Measured: Attrition will be assessed at 18 months.
Reasons for Discontinuation
Feasibility will be evaluated by measures of reasons for discontinuation regardless of clinical state, to Week 18 or later will be considered feasible.
Measured: Discontinuation will be assessed at 18 months.
To Determine the Safety of Performing a Larger Study With Similar Design.
Safety will be evaluated by measures of the number by type of protocol deviations.
Measured: Safety will be assessed at 18 months.
Evaluate the Appropriateness of the Proposed Tests of Cognitive Control Measures in Exploring the Mechanisms of Change.
Appropriateness will be evaluated by the proportion of patients who are able to complete the cognitive control assessments. As this is a feasibility study, we do not have pre-specified quantitative cutoffs.
Measured: 6 months
Secondary outcomes (1)
Efficacy of Esketamine/CBT Combination Compared to Esketamine/TAU in Reducing the Risk of Suicide.
Efficacy will be measured by the response to the MADRS (Montgomery-Asberg Depression Rating Scale). The MADRS is a 10 question assessments conducted in an interview setting.
Each item is scored from 0 to 6. Total score ranges from 0 to 60. Higher scores indicate more severe depressive symptoms.
Measured: Measured at Baseline, study day 2, study day 15, study day 30, weeks 7 - 17, week 18, week 26. The primary observation will be the last observation carried forward per protocol at Week 18.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2021
- Study start5 Mar 2021
- Primary completion30 Jun 2025
- Study completion30 Jun 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Depression and SuicideStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Esketamine:All participants will receive esketamine for MDSI (Major depression with suicidal ideation) as part of their standard care. The protocol will adhere to the FDA label for this product and the FDA-registered trials. CBT:Half of participants will be randomized to the CBT intervention, which will consist of an in-person and computer-based component (based on Good Days Ahead). In total, this will consist of 20 total sessions given over 16 weeks (the first 4 weeks of CBT will have sessions twice weekly; thereafter sessions will be held weekly). TAU only:Participants not randomized to CBT will undergo treatment as usual (TAU). These patients will undergo standard, post-hospitalization clinical treatments, which may include physician visits and psychotherapy (except for formal CBT).
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 93 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Samuel T Wilkinson, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04760652
- Sponsor's protocol ID
- 2000029473
- Other IDs
- 1265736169, 1R01MH125205-01
- Acronym
- ENDURE
- Status last verified
- Jul 2026
- First submitted
- 4 Feb 2021
- Last updated
- 16 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Wilkinson ST, Kitay BM, Macaluso M, Santucci MC, Kumpf K, Voghell C, Astorino L, Hershenberg R, Martinez-Kaigi V, Nowell T, Thase ME, Sanacora G, Rhee TG. Cognitive Behavioral Therapy Following Esketamine for Major Depression and Suicidal Ideation for Relapse Prevention: The CBT-ENDURE Randomized Trial. J Clin Psychiatry. 2026 May 4;87(2):25m16285. doi: 10.4088/JCP.25m16285.
PubMed 42095692
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CBT-ENDURE: Cognitive Behavioral Therapy Following Esketamine for Major Depression and Suicidal Ideation for Relapse Prevention
- ClinicalTrials.gov ID
- NCT04760652
- Acronym / sponsor ID
- ENDURE / 2000029473
- Conditions
- Depression and Suicide
- Keywords
- Depression, Suicide
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 93 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 5 Mar 2021 (actual)
- Primary completion
- 30 Jun 2025 (actual)
- Study completion
- 30 Jun 2025 (actual)
- First posted
- 18 Feb 2021 (actual)
- Results
- Posted 16 Sep 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a rater-blinded, randomized controlled trial. All patients will receive esketamine for treatment of Major Depression with Suicidal Ideation (MDSI). Subjects will be randomized (1:1) to receive CBT (computer-assisted) or TAU alone following esketamine.
Detailed description
Specific Aim 1: To determine the feasibility and safety of performing a larger study examining the effectiveness and mechanism of action of CBT to improve the longer-term outcomes following esketamine treatment in patients hospitalized for suicidal ideation or suicide attempt.
Specific Aim 2: To evaluate the appropriateness and utility of the proposed tests of cognitive control measures in exploring the mechanisms underlying the effects on depression of esketamine and the combination of esketamine+CBT.
Specific Aim 3: To examine the efficacy of esketamine+CBT combination compared to esketamine+TAU in reducing suicidal ideation.
In August 2022, the targeted enrollment was expanded to include outpatient participants, the anticipated enrollment was increased from 60 to 100 participants as a result.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Esketamine:All participants will receive esketamine for MDSI (Major depression with suicidal ideation) as part of their standard care. The protocol will adhere to the FDA label for this product and the FDA-registered trials. CBT:Half of participants will be randomized to the CBT intervention, which will consist of an in-person and computer-based component (based on Good Days Ahead). In total, this will consist of 20 total sessions given over 16 weeks (the first 4 weeks of CBT will have sessions twice weekly; thereafter sessions will be held weekly). TAU only:Participants not randomized to CBT will undergo treatment as usual (TAU). These patients will undergo standard, post-hospitalization clinical treatments, which may include physician visits and psychotherapy (except for formal CBT).
| Arm | Type | Receives |
|---|---|---|
| CBT Cognitive Behavioral Therapy | Active comparator | Behavioral: Cognitive Behavioral Therapy CBTParticipants will receive CBT, which will consist of in-person and computer-based component (based on Good Days Ahead). This will consist of 20 sessions given over 16 weeks. |
| TAU Treatment As Usual | Other | Other: TAUParticipants will undergo Treatment as usual (TAU). These patients will undergo standard, post-hospitalization clinical treatments, which many include physician visits and psychotherapy (except for formal CBT). |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Participants are eligible for the study if they meet all the following criteria:
Key exclusion criteria (17 listed)
- Participants are excluded if they meet any of the following criteria:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cognitive Behavioral Therapy CBTCBT: In-person and computer-based components (Good Days Ahead) First 4 weeks of CBT are twice weekly; thereafter weekly CBT | Behavioural | CBT Cognitive Behavioral Therapy |
| TAUTreatment as usual- can vary. | Other | TAU Treatment As Usual |
Primary outcome
To Determine the Feasibility of Performing a Larger Study With Similar Design by Measuring of Recruitment Rates.
Time frame: Recruitment rates will be assessed at 18 months.
Feasibility will be evaluated by measures of recruitment rates measured by attaining 80% of recruitment target will be considered feasible. Presented are those that were consented and then randomized.
To Determine the Feasibility of Performing a Larger Study With Similar Design by Measuring Attrition.
Time frame: Attrition will be assessed at 18 months.
Feasibility will be evaluated by measures of attrition rates by attaining 80% of retention will of 70% of participants will be considered feasible.
Reasons for Discontinuation
Time frame: Discontinuation will be assessed at 18 months.
Feasibility will be evaluated by measures of reasons for discontinuation regardless of clinical state, to Week 18 or later will be considered feasible.
To Determine the Safety of Performing a Larger Study With Similar Design.
Time frame: Safety will be assessed at 18 months.
Safety will be evaluated by measures of the number by type of protocol deviations.
Evaluate the Appropriateness of the Proposed Tests of Cognitive Control Measures in Exploring the Mechanisms of Change.
Time frame: 6 months
Appropriateness will be evaluated by the proportion of patients who are able to complete the cognitive control assessments. As this is a feasibility study, we do not have pre-specified quantitative cutoffs.
1 secondary outcome
Efficacy of Esketamine/CBT Combination Compared to Esketamine/TAU in Reducing the Risk of Suicide.
Time frame: Measured at Baseline, study day 2, study day 15, study day 30, weeks 7 - 17, week 18, week 26. The primary observation will be the last observation carried forward per protocol at Week 18.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42095692Wilkinson ST, Kitay BM, Macaluso M, Santucci MC, Kumpf K, Voghell C, Astorino L, Hershenberg R, Martinez-Kaigi V, Nowell T, Thase ME, Sanacora G, Rhee TG. Cognitive Behavioral Therapy Following Esketamine for Major Depression and Suicidal Ideation for Relapse Prevention: The CBT-ENDURE Randomized Trial. J Clin Psychiatry. 2026 May 4;87(2):25m16285. doi: 10.4088/JCP.25m16285.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Samuel T Wilkinson, MD principal investigator
Yale University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cognitive Behavioral Therapy CBT and TAU in people with Depression and Suicide, run by Yale University at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Sep 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To Determine the Feasibility of Performing a Larger Study With Similar Design by Measuring of Recruitment Rates. (time frame: Recruitment rates will be assessed at 18 months.). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04760652, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2026.