Ketamine + Mindfulness for Depression

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.

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

Eligibility Criteria:
Inclusion Criteria:

All participants will:

1. be between the ages of 18 and 65 years,
2. score ≥ 14 on the Hamilton Depression Rating Scale (modified Ham-D)
3. 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:

1. Presence of lifetime bipolar, psychotic, or autism spectrum; current problematic substance use (e.g., ongoing moderate-to-severe substance use disorder);
2. 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.
3. Changes made to treatment regimen within 4 weeks of baseline assessment.
4. Reading level \<6th grade as per patient self-report.
5. Patients who have received ECT in the past 2 months prior to Screening.
6. Current pregnancy or breastfeeding
7. 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.
8. Clinically significant abnormal findings of laboratory parameters \[including urine toxicology screen for unreported drugs of abuse\], vitals, or ECG.
9. 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.
10. Patients with one or more seizures without a clear and resolved etiology.
11. Patients starting hormonal treatment (e.g., estrogen) in the 3 months prior to Screening.
12. Past intolerance or hypersensitivity to ketamine.
13. Patients taking medications with known activity at the NMDA or AMPA glutamate receptor \[riluzole, amantadine, memantine, topiramate, dextromethorphan, D-cycloserine\], 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.
14. Patients taking any of the following medications: St John's Wort, theophylline, tramadol, metrizamide.
15. Patients who report meditating with mindfulness techniques \>1 hour weekly (on average) for the past 6 months or longer.