The BIO-K Study: A Single-Arm, Open-Label, Biomarker Development Clinical Trial of Ketamine for Non-Psychotic Unipolar Major Depression and Bipolar I or II Depression.

Inclusion criteria: * Ability to provide informed consent * Current psychiatric inpatient (voluntary only) or outpatient treatment * Meets Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnostic criteria for major depressive disorder, bipolar I disorder, or bipolar II disorder * Patient Health Questionnaire (PHQ-9) total score \> 15 at screening and at baseline (just prior to first acute phase ketamine infusion); * Treatment-resistant depression, as defined by failure of at least two previous antidepressant or mood stabilizing treatments within the current depressive episode * Failed antidepressant or mood stabilizing treatments can include pharmacotherapy for depression at an adequate dose for at least 8 weeks, or an acute series of at least 6 administrations of electroconvulsive therapy (ECT) * Ability to pass a comprehension assessment test related to effects of ketamine and trial objectives and criteria Exclusion Criteria: * Diagnosis of schizophrenia, schizoaffective disorder, or active psychotic symptoms * Ongoing prescription of \> 4 mg lorazepam equivalents (total) daily, or morning dosing of any benzodiazepine at the time of assessment * Currently undergoing ECT, transcranial magnetic stimulation, vagal nerve stimulation, or deep brain stimulation as either an acute or maintenance treatment of depression * Any active or unstable medical condition judged by the study psychiatrist as conferring too great a level of medical risk to allow inclusion in the study * Use or abuse of methamphetamine, cocaine, cannabis, or stimulants (prescribed and illicit) within the past 12 months * Any current abuse or dependence of alcohol or drugs (excluding nicotine and caffeine) Note: Persons will be allowed to enroll in this study if their drug or alcohol abuse/dependence is in complete (not partial) and sustained (\> 1 year) remission * History of traumatic brain injury that resulted in loss of consciousness * Developmental delay, mental retardation, or intellectual disorder * Clinical or self-reported diagnosis of delirium, encephalopathy, or related clinical diagnosis within the prior 12 months * Cognitive disorder (mild and major categories, per DSM-5) * Prior participation in another study of ketamine for depression within the prior 6 months * History of either poor antidepressive response to or poor tolerability of ketamine (any route of administration) when previously administered for treating symptoms of depression * History of hypothyroidism unless taking a stable dose of thyroid medication and asymptomatic for 6 months * Significant unstable medical condition * Hepatic insufficiency (2.5 X upper limit of normal (ULN) for aspartate aminotransferase (AST) or ALT) within 1 year of consent, past liver transplant recipient, and/or clinical diagnosis of cirrhosis of the liver * Pregnancy, or nursing * Prisoners * Involuntary psychiatric hospitalization