Ketamine as a Rapidly-Acting Antidepressant in Depressed Emergency Department Patients

Inclusion Criteria: * Medically stable as determined by the medical physician * Meets criteria for Major Depressive Disorder (MDD) based on a structured clinical Interview (MINI International Neuropsychiatric Interview). * Reports symptoms of severe depression at the time of presentation, defined as a score of 24 or greater on the MADRS. * Patients for whom a psychiatric evaluation and disposition decision has been made by emergency psychiatry staff to admit to an inpatient psychiatric unit at Bellevue Hospital Center or NYU Tisch Hospital. * Each subject must have a level of understanding sufficient to sign an informed consent stating that the treatment being offered is not FDA approved for the treatment of depression and is being provided as an off-label option. Exclusion Criteria: * Pregnancy * Inability to read or understand English * Current clinical signs of intoxication or delirium at time of study intervention * Overdose, within previous 24 hours, of any agent which would impair ketamine metabolism * Lifetime misuse/abuse of ketamine, phencyclidine (PCP),or related substances * Lifetime history of psychotic spectrum illness * First-degree relative with history of psychotic illness * Lifetime diagnosis of borderline personality disorder, or as confirmed by assessment using items #90-104 of the SCID-II (for DSM-IV). * Subjects with clinically significant abnormal findings as determined by medical history, physical examination, vital signs (blood pressure, heart rate, and respiration rate), O2 saturation measure, 12-lead ECG, clinical laboratory tests (CBC, chemistry panel, thyroid function tests), urine drug screen, and urine pregnancy test (for females of childbearing potential only). * Clinically unstable medical, surgical or neurological conditions at ED presentation * History of stroke or intracranial hypertension * History of glaucoma * Subjects with one or more seizures without a clear and resolved etiology * Current NMDA antagonist medications (eg. Amantadine, Rimantadine, Lamotrigine, Memantine, Dextromethorphan) * Known hypersensitivity to ketamine or amantadine * Anti-psychotic medications (Typicals or Atypicals), with the exception of low-dose quetiapine (total daily dose of 100mg or less). * Actively trying to commit suicide, even in a hospital setting * Current homicide risk * Unable or unwilling to give informed consent according to HIC guidelines * Unable or unwilling to provide 2 contact phone numbers or be followed up per study protocol. * Previous enrollment in this study. * Concurrent enrollment in a research protocol investigating experimental pharmacologic treatments for depression at this or any other institution.