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

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

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.

Study Overview

• Status: Completed
• Conditions: Depressive Disorder, Major
• Intervention / Treatment: Other: Cognitive behavioral therapy (CBT) and medication; Other: Psychoeducation and medication

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cognitive behavioral therapy (CBT) and medication; 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; Sixteen sessions over 14 weeks.
Active Comparator: Psychoeducation and medication; 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

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Yale University
• Investigators: Principal Investigator: Samuel Wilkinson, MD, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Actual): September 30, 2019
• Study Completion (Actual): January 15, 2020

Study Registration Dates

• First Submitted: January 19, 2017
• First Submitted That Met QC Criteria: January 20, 2017
• First Posted (Estimate): January 23, 2017

Study Record Updates

• Last Update Posted (Actual): February 5, 2020
• Last Update Submitted That Met QC Criteria: January 30, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant
• Other Study ID Numbers: 1609018450