Ketamine in the Treatment of Suicidal Depression

INCLUSION CRITERIA: * Unipolar depression with current major depressive episode (MDE). Participants may be psychiatric medication-free, or if on psychiatric medication, not responding adequately given current MDE with suicidal ideation (See 2). * Moderate to severe suicidal ideation * 18-65 years old * Participants must agree to a voluntary admission to an inpatient research unit at the New York State Psychiatric Institute (NYSPI)for the infusion(s), for a brief stay, or longer if clinically necessary. * Pre-menopausal female participants of child-bearing potential must be willing to use an acceptable form of birth control during study participation such as condoms, diaphragm, or oral contraceptive pills. * Able to provide informed consent * Participants 61-65 years old must score a 25 or higher on the Mini-Mental State Examination (MMSE) at screening. EXCLUSION CRITERIA: * Unstable medical condition or neurological illness, including baseline hypertension (BP\>140/90) or significant history of cardiovascular illness. * Significant ECG abnormality * Pregnant or lactating * Diagnosis of bipolar disorder or psychotic disorder * Contraindication to any study treatment. * Inadequate understanding of English. * Prior ineffective trial of or adverse reaction to Ketamine or Midazolam. * Opiate use greater than total daily dose of 20mg Oxycodone or equivalent during the 3 days pre-infusion. * A diagnosis of sleep apnea.