Ketamine-Assisted Mindfulness-Based Cognitive Therapy for Depression: A Pilot Study

The purpose of this study is to assess the feasibility of combining IV ketamine, a rapid acting antidepressant, with a course of Mindfulness-Based Cognitive Therapy (MBCT), for the initial and maintenance treatment of depression.

Study Overview

• Status: Active, not recruiting
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Other: Combination use of MBCT and IV Ketamine

Detailed Description

The purpose of this study is to assess the feasibility of combining IV ketamine, a rapid acting antidepressant, with a course of Mindfulness-Based Cognitive Therapy (MBCT), for the initial and maintenance treatment of depression. Both ketamine and MBCT are used for treatment of depression, however, the combination of ketamine and psychotherapy has been studied mostly for drug addiction. Despite its rapid onset and effectiveness for depression, ketamine is most effective in the short term. MBCT is a therapeutic approach that combines cognitive behavioral techniques (CBT) with mindfulness strategies in order to help individuals better understand and manage their thoughts and emotions that can both decrease and prevent the relapse of the symptoms of depression. The aim of this pilot study is to embed one infusion of ketamine in the MBCT treatment. Our hypothesis is that the initial positive effect of ketamine will help patients engage in the behavioral therapy, which itself provides cognitive/emotion control tools to prevent relapses of depression.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Harding Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults age 18-65
• A current diagnosis of major depressive disorder according to DSM-5 criteria per MINI interview
• Moderate to severe level of current depressive symptoms (MADRS score ≥20)
• Failure of at least one adequate trial of antidepressant medication (defined as: therapeutic doses of antidepressant medication for ≥ 6 weeks)
• No adverse reactions to ketamine
• Capacity to consent and comply with study procedures, including sufficient proficiency in English

Exclusion Criteria:

• Meets DSM-5 criteria for bipolar disorder, schizophrenia, any psychotic illness, including substance-induced psychosis, active PTSD, dissociative disorders and current substance-induced mood disorder, OCD, eating disorder, panic disorder.
• Suicide attempt in the past 4 weeks or current risk of suicide
• Current alcohol or drug substance use disorder according to DSM-5
• Cognitive- or intellectual impairments which would interfere with participation in MBCT or assessments including meeting criteria for Delirium, Dementia, Amnesia, Cognitive Disorders,
• Personality Disorders (borderline, antisocial, paranoid, schizoid, histrionic) that may interfere with treatment
• Previous participation in MBCT or MBSR group
• Pregnant or planning to become pregnant during the study period
• Heart disease as indicated by history, abnormal ECG, previous cardiac surgery.
• Hypertension (>160/100)
• Unstable physical disorders which might make participation hazardous such as history of AIDS, known lab abnormalities, active hepatitis or other liver disease with elevated transaminase levels (< 2-3 X upper limit of normal will be considered acceptable if PT/PTT is normal), renal failure (creatinine > 2, BUN >40), or untreated diabetes.
• Previous history of ketamine misuse or abuse, or a history of an adverse reaction/experience with prior exposure to ketamine
• BMI > 32
• History of documented obstructive sleep apnea
• On psychotropic or other medications whose effect could be disrupted by participation in the study or not allowed during the study (such as monoamine oxidase inhibitors).
• Patient unable or unlikely to comply with the study protocol or for any other conditions that might indicate that the patient is unsuitable for the study as judged by the investigator
• Positive urine drug screen, except for marijuana or benzodiazepine if prescribed.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketamine-MBCT Intervention; One Arm: Combination of MBCT with a single ketamine infusion	Other: Combination use of MBCT and IV Ketamine; Group with Major Depression who will receive a single dose of IV Ketamine embedded within a course of MBCT.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in MADRS score	Response defined a ≥50% reduction in depressive symptoms as measured of standardized measures; remission defined as decrease of depression scores below cut-off for the scale	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in PHQ9 score	Response defined a ≥50% reduction in depressive symptoms on the PHQ9	12 months
Correlation between MADRS/PHQ9 score and Mystic experience scores	analysis of possible correlation between depression scales scores and mystic experience during the ketamine infusion	12 months

Collaborators and Investigators

• Sponsor: Ohio State University

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2022
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2026

Study Registration Dates

• First Submitted: April 3, 2023
• First Submitted That Met QC Criteria: July 10, 2023
• First Posted (Actual): July 18, 2023

Study Record Updates

• Last Update Posted (Actual): August 11, 2025
• Last Update Submitted That Met QC Criteria: August 7, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Ketamine; Mindfulness-Based Cognitive Therapy; Major depressive disorder
• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Anesthetics; Central Nervous System Depressants; Sensory System Agents; Analgesics; Neurotransmitter Agents; Anesthetics, Intravenous; Anesthetics, General; Excitatory Amino Acid Agents; Anesthetics, Dissociative; Excitatory Amino Acid Antagonists; Ketamine
• Other Study ID Numbers: 2020H0374

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to share our data with other researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No