Ketamine-Assisted Psychotherapy (KAP) Compared to Ketamine Alone for the Treatment of Depression

Inclusion Criteria * Written informed consent (and assent when applicable) obtained from subject and ability for subject to comply with the requirements of the study. * Age 18-90 years * Participant in good physical health * Participants may be on medications for depression as long as they remain on a stable dose. * A score of at least 20 on the 10 item Montgomery-Asberg Depression Scale at screening, corresponding to at least moderate current depression severity. * Meets criteria for major depressive disorder (MDD) in current major depressive episode (MDE) according to DSM-5 * Women of child-bearing potential must have a negative pregnancy test at screening and prior to ketamine infusion Exclusion Criteria * Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study. * Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data. * Any unstable medical illnesses including hepatic, renal, gastroenterological, respiratory, cardiovascular (including ischemic heart disease and uncontrolled hypertension); endocrinologic, neurologic, immunologic, or hematologic disease * Clinically significant abnormalities of laboratories, physical examination, or ECG * Substance drug or alcohol use disorder in the prior 12 months * History of hypersensitivity to ketamine or esketamine * Lifetime history of schizophrenia, schizoaffective disorder, bipolar I or II disorder * Presence of psychotic symptoms in the current MDE, or lifetime psychotic disorder * Recreational ketamine or phencyclidine use in the last year * Previous non-response to clinical or research ketamine or esketamine administration * Concurrent treatment with ECT, TMS, or VNS in the current MDE * BMI \> 35 * Significant suicidal ideation as determined by a C-SSRS score \>2 in past 30 days * History of suicide attempt or self harm in the prior 2 years * SBP \> 165 or DBP \> 95 on infusion day * MoCA score \< 23