Depression and Suicide
Conditions
Keywords
Depression, Suicide
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.
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.
Interventions
BEHAVIORALCognitive Behavioral Therapy CBT
CBT: In-person and computer-based components (Good Days Ahead) First 4 weeks of CBT are twice weekly; thereafter weekly CBT
OTHERTAU
Treatment as usual- can vary.
Sponsors
Yale University
National Institute of Mental Health (NIMH)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Rater blinded
Intervention 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).
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Determine the Feasibility of Performing a Larger Study With Similar Design by Measuring of Recruitment Rates. | 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. | 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 | 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. | 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. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORSamuel T Wilkinson, MD
Yale University
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 34.9 years |
| Education College graduate (Bachelor's) | 29 Participants |
| Education High school graduate | 3 Participants |
| Education Master's degree | 9 Participants |
| Education Professional or graduate degree (beyond Master's degree) | 6 Participants |
| Education Some college | 14 Participants |
| Education Some high school | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 82 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Marital Status Civil union/cohabitating | 3 Participants |
| Marital Status Divorced | 16 Participants |
| Marital Status Married | 17 Participants |
| Marital Status Never married | 21 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 42 Participants |
| Region of Enrollment United States | 47 participants |
| Sex/Gender, Customized Sex/Gender Female | 27 Participants |
| Sex/Gender, Customized Sex/Gender Male | 33 Participants |
| Sex/Gender, Customized Sex/Gender Other | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 47 | 0 / 46 |
| other Total, other adverse events | 41 / 47 | 39 / 46 |
| serious Total, serious adverse events | 13 / 47 | 9 / 46 |
Outcome results
None listed