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.

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.

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.

There is no plan to share our data with other researchers