Cognitive Behavioral Therapy After Esketamine for Depression with Suicidal Ideation

(ENDURE Trial)

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

100 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of this treatment for depression with suicidal thoughts?

Research shows that therapies like Cognitive Behavioral Therapy (CBT) and Mindfulness-Based Cognitive Therapy (MBCT) are effective in reducing symptoms of depression and preventing relapse. These therapies have been shown to help manage suicidal thoughts, especially when combined with other treatments. ^{1 2 3 4 5}

Is Cognitive Behavioral Therapy (CBT) safe for humans?

Research shows that Cognitive Behavioral Therapy (CBT) is generally safe for humans. It is used to treat depression and reduce suicide risk, with studies indicating low rates of deterioration in patients undergoing CBT. ^{6 7 8 9 10}

How is Cognitive Behavioral Therapy After Esketamine for Depression with Suicidal Ideation different from other treatments?

Cognitive Behavioral Therapy (CBT) after Esketamine is unique because it combines a fast-acting medication, Esketamine, which is administered as a nasal spray to quickly reduce symptoms of depression and suicidal thoughts, with CBT, a structured talk therapy that helps patients change negative thought patterns. This combination aims to provide both immediate relief and long-term coping strategies, which is different from traditional antidepressants that may take weeks to show effects. ^{11 12 13 14 15}

Research Team

Samuel T Wilkinson, MD

Principal Investigator

Yale University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

[Psychotherapy of depression]. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

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

3. United States pubmed.ncbi.nlm.nih.gov

The long-term effects of mindfulness-based cognitive therapy as a relapse prevention treatment for major depressive disorder. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Mindfulness-Based Cognitive Therapy for Preventing Suicide in Military Veterans: A Randomized Clinical Trial. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Inadequate response to therapy as a predictor of suicide. [2007]

6. United States pubmed.ncbi.nlm.nih.gov

Pilot trial of post-admission cognitive therapy: Inpatient program for suicide prevention. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Rationale and study design of a trial of mindfulness-based cognitive therapy for preventing suicidal behavior (MBCT-S) in military veterans. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Cognitive behavioral therapy for depression. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

The significance of cognitive-behavioral therapy on suicide: An umbrella review. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Rates and Predictors of Deterioration in a Trial of Internet-Delivered Cognitive Behavioral Therapy for Reducing Suicidal Thoughts. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

New vertebral fractures after osteoporotic vertebral compression fracture between balloon kyphoplasty and nonsurgical treatment PRISMA. [2022]

12. Germany pubmed.ncbi.nlm.nih.gov

Long-term management of corrosive esophageal stricture with balloon dilation in children. [2021]

13. England 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. [2023]

14. England 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. [2023]

15. Germany pubmed.ncbi.nlm.nih.gov

[Balloon kyphoplasty in the treatment of back pain]. [2018]