Cognitive Therapy to Sustain the Antidepressant Effects of Intravenous Ketamine in Treatment-resistant Depression

Study Overview
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Brief Summary
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The goals of this study are: 1) to investigate the efficacy of combining ketamine with intensive cognitive behavioral therapy (CBT) to sustain the antidepressant effects of ketamine; and 2) to determine ketamine's delayed effects on learning and memory, and to explore the relationship between any ketamine-induced changes in learning and memory and duration of antidepressant efficacy, with and without CBT augmentation. Subjects with a diagnosis of MDD who are treatment-resistant to at least 2 antidepressants and have chosen to pursue clinical ketamine treatment at Yale Psychiatric Hospital will be recruited for the study.

Official Title
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Cognitive Therapy to Sustain the Antidepressant Effects of Intravenous Ketamine in Treatment-resistant Depression: a Randomized Controlled Trial

Conditions
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Depressive Disorder, Major

Intervention / Treatment
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* Other: Cognitive behavioral therapy (CBT) and medication
* Other: Psychoeducation and medication


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Suffering from a major depressive episode based on Diagnostic and Statistical manual (DSM) 5 criteria and having failed one or more standard antidepressant treatments during the current episode Hamilton Depression Rating Scale (17-HAM-D) score of 21 or more prior to ketamine treatment. Planned clinical treatment with ketamine at Yale Psychiatric Hospital (YPH) As the purpose of this study is to determine the feasibility and efficacy of CBT to sustain the antidepressant effects of ketamine, only those who achieve a clinical response (i.e., 50% reduction in depression symptoms, as measured by the Montgomery-Asberg Depressive Rating Scale (MADRS) will be eligible for randomization. Patients must be treatment resistant to at least two drugs used to treat depression. Exclusion Criteria: Any Axis I or Axis II Disorder, which at screening is clinically predominant to their depressive episode or has been predominant to their depressive episode at any time within 6 months prior to screening Active suicidal thoughts with a plan Current or recent (<6 months ago) substance use disorder Non-affective psychosis (such as schizophrenia or schizoaffective disorder) Inability to speak English fluently A clinically significant abnormality on the screening physical examination that might affect safety, study participation, or confound interpretation of study results Dementia, delirium, or any other neurological or mental disease that might affect cognition or the ability to meaningfully participate in cognitive behavioral therapy (CBT).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cognitive behavioral therapy (CBT) and medication<br>Following clinical ketamine treatment, the intervention includes sixteen CBT sessions over 14 weeks. In addition, standard of care medications for treatment of depression, will be prescribed by the principal investigator or by a psychiatrist unaffiliated with the trial. Participants will remain on the medication they were prescribed when they entered the study and will be expected not to adjust the medication unless clinically urgent. | Other: Cognitive behavioral therapy (CBT) and medication<br>* Sixteen sessions over 14 weeks.<br>|
| Active Comparator: Psychoeducation and medication<br>Following clinical ketamine treatment, the intervention includes psychoeducational sessions over 14 weeks.In addition, standard of care medications for treatment of depression, will be prescribed by the principal investigator or a by psychiatrist unaffiliated with the trial. | Other: Psychoeducation and medication<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to relapse of depression measured by the Montgomery-Asberg Depressive Rating Scale (MADRS) score. | Relapse is defined as less than 50% improvement in MADRS compared to baseline MADRS score. The median time to relapse is the time at which the 50th percentile of participants relapses. | Enrollment to 17 week follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cognitive flexibility-working memory | Measured by n-back task | Before the first ketamine treatment and 24 hours following the last ketamine treatment. | 
| Change in cognitive flexibility-executive function | Measured by set shifting task (COGSTATE test) | Before the first ketamine treatment and 24 hours following the last ketamine treatment. |