Cognitive Behavioral Therapy Following Esketamine for Major Depression and Suicidal Ideation for Relapse Prevention

NCT04760652 | Completed DMC

• 3 other identifiers: 200002947312657361691R01MH125205-01
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Depression and Suicide

Keywords

Depression; Suicide

Outcome Measures

Primary Outcomes (5)

• 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.

  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.

  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.

  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.

  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.

  The appropriateness will be assessed at the end of study (18 months).

Secondary Outcomes (1)

• Efficacy of esketamine/CBT combination compared to esketamine/TAU in reducing the risk of suicide.

  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.

Other Outcomes (7)

• To evaluate the depression assessments BDI-II (Beck Depression Inventory).

  BDI-II will be measured at Baseline, study day 2, study day 15, study day 30, weeks 7 - 17, week 18, week 26. The primary assessment of this outcome will be at Week 18.

• To evaluate the depression assessments CGI (Clinical Global Impression for Severity of Suicidality).

  CGI will be measured at Baseline, study day 2, study day 15, study day 30, weeks 7 - 17, week 18, week 26. The primary assessment of this outcome will be at Week 18.

• To evaluate the Suicide Ideation assessments CSSRS (COLUMBIA-SUICIDE SEVERITY RATING SCALE).

  The CSSRS will be measured at Baseline, study day 2, study day 15, study day 30, weeks 7 - 17, week 18, week 26. The primary assessment of this outcome will be at Week 18.

Study Arms (2)

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.

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).

Behavioral: Cognitive Behavioral Therapy CBT

Interventions

Cognitive Behavioral Therapy CBT BEHAVIORAL

CBT: In-person and computer-based components (Good Days Ahead) First 4 weeks of CBT are twice weekly; thereafter weekly CBT

CBT Cognitive Behavioral Therapy; TAU Treatment As Usual

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• Previous Esketamine or ketamine treatment that did not produce a clinical response as outlined below.
• treatments with Esketamine at a dose of 56 mg or more with no clinical response
• 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

Sponsors & Collaborators

• Yale University: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (3)

UAB Medicine | Heersink School of Medicine

Birmingham, Alabama, 35294, United States

Location

Yale University

New Haven, Connecticut, 06511, United States

Location

Emory University

Atlanta, Georgia, 30329, United States

Location

MeSH Terms

Conditions

Depression; Suicide

Interventions

Cognitive Behavioral Therapy

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Self-Injurious Behavior

Intervention Hierarchy (Ancestors)

Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities

Study Officials

• Samuel T Wilkinson, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Rater blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: February 4, 2021
• First Posted: February 18, 2021
• Study Start: March 5, 2021
• Primary Completion: June 30, 2025
• Study Completion: June 30, 2025
• Last Updated: July 14, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)