Ketamine + Mindfulness for Depression

Study Overview
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Brief Summary
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In this project, the investigators will administer a single infusion of IV ketamine to depressed patients and randomize the patients to receive either a) usual/typical infusion conditions or b) mindfulness training and exercises in conjunction with the infusion. Investigators will test whether the conjunction of ketamine + mindfulness enhances the reductions in depression following a single ketamine infusion.

Detailed Description
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NOTE: The study's target sample size was revised after beginning the study, based on a revised available budget.

Official Title
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Ketamine + Mindfulness for Depression

Conditions
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Depression, Unipolar

Intervention / Treatment
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* Drug: Intravenous Ketamine
* Behavioral: Brief Mindfulness Exercises
* Behavioral: Academic Exercises


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All participants will: be between the ages of 18 and 65 years, score ≥ 14 on the Hamilton Depression Rating Scale (modified Ham-D) possess a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign an informed consent document Exclusion Criteria: All participants: Presence of lifetime bipolar, psychotic, or autism spectrum; current problematic substance use (e.g., ongoing moderate-to-severe substance use disorder); Acute suicidality or other psychiatric crises requiring treatment escalation. We will use the Columbia Suicide Severity Rating Scale (CSSRS) as both an initial exclusion criteria (CSSRS Baseline/Screening Version for past 1month period) and as grounds for rescue/removal (CSSRS Since Last Visit form). The CSSRS will be administered using a paper form by an experienced and thoroughly trained clinical assessor on the study team. Subjects with CSSRS suicide ideation scores scored yes on items 4 (active suicidal ideation with some intent to act) and/or 5 (active suicidal ideation with specific plan and intent) will be excluded from the study, and if enrolled, will be exited from the study and referred immediately to the nearest emergency mental health facility for additional thorough assessment and appropriate treatment referral. Changes made to treatment regimen within 4 weeks of baseline assessment. Reading level <6th grade as per patient self-report. Patients who have received ECT in the past 2 months prior to Screening. Current pregnancy or breastfeeding Patients must be reasonable medical candidates for ketamine infusion, as determined by a physician co-investigator. Serious, unstable medical illnesses including respiratory [obstructive sleep apnea, or history of difficulty with airway management during previous anesthetics], cardiovascular [including ischemic heart disease and uncontrolled hypertension], and neurologic [including history of severe head injury] will be exclusions. Clinically significant abnormal findings of laboratory parameters [including urine toxicology screen for unreported drugs of abuse], vitals, or ECG. Uncontrolled or poorly controlled hypertension, as determined by a physician co-investigator's review of vitals collected during screening and any other relevant medical history/records. Patients with one or more seizures without a clear and resolved etiology. Patients starting hormonal treatment (e.g., estrogen) in the 3 months prior to Screening. Past intolerance or hypersensitivity to ketamine. Patients taking medications with known activity at the NMDA or AMPA glutamate receptor [riluzole, amantadine, memantine, topiramate, dextromethorphan, Dcycloserinem, Sonata, Ambien, Lunesta, Acamprosate ], or the mu-opioid receptor [opiate medications--morphine, oxycodone, heroin, fentanyl)]. However, lamotrigine will not be a study exclusion given that it has been shown not to impact ketamine's safety profile or its antidepressant efficacy. Patients taking any of the following medications: St John's Wort, theophylline, tramadol, metrizamide. Patients who report meditating with mindfulness techniques >1 hour weekly (on average) for the past 6 months or longer.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intravenous Ketamine + Mindfulness Exercises<br> | Drug: Intravenous Ketamine<br>* Single infusion of intravenous racemic ketamine (0.5mg/kg over 40min)<br>Behavioral: Brief Mindfulness Exercises<br>* 30min guided training in mindfulness meditation immediately prior to infusion<br>|
| Active Comparator: Intravenous Ketamine + Academic Exercises<br> | Drug: Intravenous Ketamine<br>* Single infusion of intravenous racemic ketamine (0.5mg/kg over 40min)<br>Behavioral: Academic Exercises<br>* 30min of mental math and other academic cognitive puzzles completed silently/mentally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montgomery-Asberg Depression Rating Scale | Clinician-rated depression (range: 0-60; higher scores = worse outcome) | 24hrs post-intervention | 
| Montgomery-Asberg Depression Rating Scale | Clinician-rated depression (range: 0-60; higher scores = worse outcome) | 5 days post-intervention | 
| Montgomery-Asberg Depression Rating Scale | Clinician-rated depression (range: 0-60; higher scores = worse outcome) | 12 days post-intervention | 
| Montgomery-Asberg Depression Rating Scale | Clinician-rated depression (range: 0-60; higher scores = worse outcome) | 21 days post-intervention | 
| Montgomery-Asberg Depression Rating Scale | Clinician-rated depression (range: 0-60; higher scores = worse outcome) | 30 days post-intervention | 
| State Mindfulness Scale | Self-reported mindfulness (range 21-105; higher scores = more mindfulness) | 80min post-infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| modified Hamilton Depression Rating Scale | Clinician-rated depression (range: 0-52; higher scores = worse outcome) | 24hrs post-intervention | 
| modified Hamilton Depression Rating Scale | Clinician-rated depression (range: 0-52; higher scores = worse outcome) | 5 days post-intervention | 
| modified Hamilton Depression Rating Scale | Clinician-rated depression (range: 0-52; higher scores = worse outcome) | 12 days post-intervention | 
| modified Hamilton Depression Rating Scale | Clinician-rated depression (range: 0-52; higher scores = worse outcome) | 21 days post-intervention | 
| modified Hamilton Depression Rating Scale | Clinician-rated depression (range: 0-52; higher scores = worse outcome) | 30 days post-intervention | 
| Quick Inventory of Depressive Symptoms | Self-reported depression (range: 0-27; higher scores = worse outcome) | 24hrs post-intervention | 
| Quick Inventory of Depressive Symptoms | Self-reported depression (range: 0-27; higher scores = worse outcome) | 5 days post-intervention | 
| Quick Inventory of Depressive Symptoms | Self-reported depression (range: 0-27; higher scores = worse outcome) | 12 days post-intervention | 
| Quick Inventory of Depressive Symptoms | Self-reported depression (range: 0-27; higher scores = worse outcome) | 21 days post-intervention | 
| Quick Inventory of Depressive Symptoms | Self-reported depression (range: 0-27; higher scores = worse outcome) | 30 days post-intervention | 
| Hood Mysticism Scale | clinician-administered to assess mystical experiences (range: -64 to +64; higher scores = greater mystical experience) | infusion +40min | 
| Mindful Attention Awareness Scale | self-reported trait mindfulness (range: 1-6; higher scores=greater mindfulness) | 24hrs post-intervention | 
| Mindful Attention Awareness Scale | self-reported trait mindfulness (range: 1-6; higher scores=greater mindfulness) | 5 days post-intervention | 
| Mindful Attention Awareness Scale | self-reported trait mindfulness (range: 1-6; higher scores=greater mindfulness) | 12 days post-intervention | 
| Mindful Attention Awareness Scale | self-reported trait mindfulness (range: 1-6; higher scores=greater mindfulness) | 21 days post-intervention | 
| Mindful Attention Awareness Scale | self-reported trait mindfulness (range: 1-6; higher scores=greater mindfulness) | 30 days post-intervention | 
| Daily Spiritual Experience Scale | self-reported spiritual experiences (range: 0-75; higher scores=greater spiritual experience) | 5 days post-intervention | 
| Daily Spiritual Experience Scale | self-reported spiritual experiences (range: 0-75; higher scores=greater spiritual experience) | 12 days post-intervention | 
| Daily Spiritual Experience Scale | self-reported spiritual experiences (range: 0-75; higher scores=greater spiritual experience) | 21 days post-intervention | 
| Daily Spiritual Experience Scale | self-reported spiritual experiences (range: 0-75; higher scores=greater spiritual experience) | 30 days post-intervention |