Cognitive Behavioral Therapy After Esketamine for Depression with Suicidal Ideation

(ENDURE Trial)

No longer recruiting at 2 trial locations

Overseen By Cindy Voghell

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Yale University

Must be taking: Esketamine

Disqualifiers: Substance use, Bipolar, Schizophrenia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 38

Duration: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding Cognitive Behavioral Therapy (CBT) after esketamine treatment can better assist individuals with Major Depression and Suicidal Thoughts. All participants will initially receive esketamine, a medication for severe depression. Subsequently, some participants will also undergo CBT, a type of talk therapy, while others will receive standard care without formal CBT. Suitable candidates have major depressive disorder, were recently hospitalized for suicidal thoughts or attempts, and have a doctor's recommendation for esketamine treatment. As an unphased trial, this study provides participants the chance to contribute to innovative research that could enhance future treatment options.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that cognitive behavioral therapy (CBT) is generally well-received by patients. It helps manage mental health issues like depression and anxiety by changing negative thoughts and behaviors.

Although CBT is a common and safe treatment, discussing any concerns with a healthcare provider is important. This trial will use CBT alongside esketamine, a medication for depression. Both treatments are considered safe, but individual experiences can differ. Always consult a medical professional to determine the best options. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using Cognitive Behavioral Therapy (CBT) after esketamine treatment for depression with suicidal ideation because it offers a unique combination of therapies. Unlike standard treatments like medication and psychotherapy, CBT is structured and goal-oriented, focusing on changing thought patterns and behaviors. This trial is exploring how CBT, when combined with the fast-acting effects of esketamine, could potentially provide both immediate relief and long-term benefits. This approach could be especially beneficial in managing suicidal thoughts more effectively than traditional treatments alone.

What evidence suggests that this trial's treatments could be effective for Major Depression with Suicidal Ideation?

Research has shown that Cognitive Behavioral Therapy (CBT), which participants in this trial may receive, effectively treats depression. It helps individuals identify and change negative thoughts and behaviors. Studies have found that CBT reduces depression symptoms by teaching coping strategies. This practical therapy focuses on changing behavior through methods like positive reinforcement and improved communication. By addressing irrational fears and encouraging positive actions, CBT enables individuals to manage their depression more effectively. ^{6 7 8 9 10}

Who Is on the Research Team?

Samuel T Wilkinson, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

Adults aged 18-65 with major depression and suicidal thoughts, who are recommended for esketamine treatment, can join. They must be willing to use contraception and follow the trial procedures. Excluded are those pregnant or breastfeeding, with certain cognitive disorders, no response to prior ketamine treatments, substance abuse issues within the last 6 months, or other serious medical/psychiatric conditions.

Inclusion Criteria

Written informed consent before any study procedures are performed

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

Recommended by a physician for esketamine treatment

Exclusion Criteria

I have tried Esketamine or ketamine before, and it didn't work for me.

I am unable to understand and agree to the study's details on my own.

You have been actively using drugs (except for tobacco) within the past 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive esketamine for treatment of Major Depression with Suicidal Ideation, followed by randomization to CBT or TAU

16 weeks

20 sessions (in-person and computer-based for CBT group)

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Regular assessments at weeks 18 and 26

What Are the Treatments Tested in This Trial?

Interventions

• Cognitive Behavioral Therapy

Trial Overview The study tests if Cognitive Behavioral Therapy (CBT) after esketamine treatment helps prevent relapse in major depression with suicidal ideation. Participants will either receive computer-assisted CBT or Treatment As Usual (TAU) randomly after their initial esketamine therapy.

How Is the Trial Designed?

Group I: TAU Treatment As Usual Experimental Treatment 1 Intervention

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).

Group II: CBT Cognitive Behavioral Therapy Active Control 1 Intervention

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.

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

In a study of 25 patients with acute vertebral compression fractures (AVCF) treated with either bipedicular (BPKP) or unipedicular (UPKP) percutaneous kyphoplasty, both methods showed similar overall clinical efficacy after 12 months, with no complications reported.

However, patients in the BPKP group experienced significantly lower pain scores (VAS) at the 12-month follow-up and had more symmetrical and uniform distribution of bone cement compared to the UPKP group, suggesting BPKP may be the preferred approach for better long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bipedicular percutaneous kyphoplasty versus unipedicular percutaneous kyphoplasty in the treatment of asymmetric osteoporotic vertebral compression fractures: a case control study. Liu, L., Song, F., Shang, J., et al.[2023]

Outpatients with mood disorders who committed suicide attended significantly fewer cognitive therapy sessions and had a higher dropout rate (88% vs. 53%) compared to those who did not commit suicide, indicating that engagement in therapy is crucial.

Patients who committed suicide exhibited higher levels of hopelessness at the end of therapy, suggesting that inadequate response to treatment and premature termination are important risk factors for suicide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inadequate response to therapy as a predictor of suicide. Dahlsgaard, KK., Beck, AT., Brown, GK.[2007]

Cognitive Behavioral Therapy (CBT) is an effective treatment for all levels of major depression, proving to be as effective and more durable than medication alone.

Combining CBT with medication can enhance treatment response and prolong benefits, especially when CBT is introduced after successful pharmacotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive behavioral therapy for depression. Sudak, DM.[2022]

In a study comparing standard balloon kyphoplasty (BKP) and the Tektona® method for treating osteoporotic vertebral compression fractures, both methods significantly restored vertebral body height after treatment, with BKP achieving a height restoration of 93.06% compared to 87.71% for Tektona®.

While both methods showed similar effectiveness in height restoration, Tektona® may offer advantages in preserving bone, suggesting it could be a promising alternative to BKP, although further biomechanical and clinical studies are needed to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Height and volume restoration in osteoporotic vertebral compression fractures: a biomechanical comparison of standard balloon kyphoplasty versus Tektona® in a cadaveric fracture model. Krüger, A., Bäumlein, M., Knauf, T., et al.[2023]

Mindfulness-Based Cognitive Therapy for Preventing Suicide Behavior (MBCT-S) did not significantly delay the time to a suicide event compared to treatment-as-usual (eTAU), but it did reduce the total number of suicide events from 92 in eTAU to 56 in MBCT-S, indicating a potential benefit in preventing suicide occurrences.

MBCT-S also showed promising results by significantly reducing the proportion of participants attempting suicide and decreasing the number of psychiatric hospitalizations, suggesting it may enhance overall safety and efficacy in suicide prevention strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mindfulness-Based Cognitive Therapy for Preventing Suicide in Military Veterans: A Randomized Clinical Trial. Interian, A., Chesin, MS., Stanley, B., et al.[2022]

A pilot trial involving 36 military personnel hospitalized after a suicide attempt tested Post-Admission Cognitive Therapy (PACT), which showed promising results in improving depression and PTSD symptoms compared to enhanced usual care.

While there was no significant difference in the rate of repeat suicide attempts between the two groups, a higher percentage of participants receiving PACT experienced clinically significant improvements in depression (100% vs. 78%) and PTSD symptoms (100% vs. 38%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot trial of post-admission cognitive therapy: Inpatient program for suicide prevention. LaCroix, JM., Perera, KU., Neely, LL., et al.[2022]

In a study involving 418 adults with suicidal ideation, the internet-based cognitive behavioral therapy (CBT) intervention 'Living with Deadly Thoughts' showed a lower rate of reliable deterioration (7%) compared to an attention control group (14%), indicating it is a safer option for suicide prevention.

The analysis found that initial severity of suicidal thinking was linked to lower odds of deterioration, while other psychological and demographic factors did not significantly affect deterioration rates, reinforcing the safety of internet-based CBT interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rates and Predictors of Deterioration in a Trial of Internet-Delivered Cognitive Behavioral Therapy for Reducing Suicidal Thoughts. Batterham, PJ., Christensen, H., Calear, AL., et al.[2022]

Cognitive therapy effectively addresses key issues in suicidal patients, such as perfectionism, social sensitivity, and hopelessness, by helping them develop constructive thinking patterns.

The therapy involves planning activities and tracking negative thoughts, which can lead to a decrease in feelings of hopelessness and improve overall mental health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive therapy for the suicidal patient: a case study. Reilly, CE.[2019]

Citations

1. northstarcounselingli.com northstarcounselingli.com/types-of-therapy/

Types of Therapy/ Approach Cognitive Behavioral Therapy (CBT); Dialectical Behavior Therapy (DBT); Rational Emotive Behavior Therapy (REBT); Mindfulness; Gestalt Therapy ...

2. washington-psychwellness.com washington-psychwellness.com/therapy/8-types-of-cognitive-behavior-therapy/

The 8 Types of Cognitive Behavior Therapy A CBT therapist works to help clients assess, recognize, and deal with problematic and dysfunctional ways of thinking, feeling, and behaving.

3. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK609098/

Behavioral Therapy - StatPearls - NCBI Bookshelf - NIH Behavioral therapy is a practical approach to modifying behavior using techniques such as reinforcement, enhanced communication, shaping, and modeling.

4. anxietyinstitute.com anxietyinstitute.com/services/therapy-types/

Understanding Therapy Names: CBT, DBT, ACT, and More Through techniques like cognitive restructuring and behavioral activation, CBT empowers individuals to challenge irrational fears and develop coping strategies.

5. healthline.com healthline.com/health/behavioral-therapy

Behavioral Therapy: Definition, Types & Effectiveness Behavioral therapy is an umbrella term for therapies that treat mental health disorders. It identifies and helps change self-destructive or unhealthy ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8489050/

Cognitive–behavioral therapy for management of mental ... Cognitive–behavioral therapy (CBT) helps individuals to eliminate avoidant and safety-seeking behaviors that prevent self-correction of faulty beliefs.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2888910/

Cognitive Behavior Therapy for Suicide Prevention (CBT-SP) Thus, CBT-SP is designed to help adolescents use more effective means of coping when faced with their stressors and problems that trigger suicidal crises.

8. en.wikipedia.org en.wikipedia.org/wiki/Cognitive_behavioral_therapy

Cognitive behavioral therapy Cognitive behavioral therapy (CBT) is a form of psychotherapy that aims to reduce symptoms of various mental health conditions, primarily depression, ...

9. frontiersin.org frontiersin.org/journals/psychology/articles/10.3389/fpsyg.2025.1672957/full

The efficacy of cognitive behavioral therapy on reducing ... CBT helps individuals identify, challenge, and reframe suicide-related maladaptive cognitions—such as “life is hopeless” or “my problems are unsolvable”—thereby ...

10. mirecc.va.gov mirecc.va.gov/visn16/docs/therapists_guide_to_brief_cbtmanual.pdf

A Provider's Guide to Brief Cognitive Behavioral Therapy CBT combines cognitive and behavioral therapies and has strong empirical support for treating mood, sleep, chronic pain, and anxiety disorders (Hoffman & Otto, ...