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

• Sponsor: Yale University (Other)
• Overall Status: Completed
• CT.gov ID: NCT03027362
• Collaborator: (none)
• Enrollment: 28
• Location: 1
• Arms: 2
• Actual Duration (Months): 36.4
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Depressive Disorder, Major	Other: Cognitive behavioral therapy (CBT) and medication; Other: Psychoeducation and medication	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Cognitive Therapy to Sustain the Antidepressant Effects of Intravenous Ketamine in Treatment-resistant Depression: a Randomized Controlled Trial
• Actual Study Start Date: Jan 1, 2017
• Actual Primary Completion Date: Sep 30, 2019
• Actual Study Completion Date: Jan 15, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Time to relapse of depression measured by the Montgomery-Asberg Depressive Rating Scale (MADRS) score. [Enrollment to 17 week follow-up]

   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.

Secondary Outcome Measures

1. Change in cognitive flexibility-working memory [Before the first ketamine treatment and 24 hours following the last ketamine treatment.]

   Measured by n-back task

2. Change in cognitive flexibility-executive function [Before the first ketamine treatment and 24 hours following the last ketamine treatment.]

   Measured by set shifting task (COGSTATE test)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale University	New Haven	Connecticut	United States	06511

Sponsors and Collaborators

• Yale University

Investigators

• Principal Investigator: Samuel Wilkinson, MD, Yale University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT03027362
• Other Study ID Numbers: 1609018450
• First Posted: Jan 23, 2017
• Last Update Posted: Feb 5, 2020
• Last Verified: Jan 1, 2020

• Additional relevant MeSH terms: Depressive Disorder; Depressive Disorder, Treatment-Resistant; Depressive Disorder, Major

Study Results

No Results Posted as of Feb 5, 2020