Efficacy of Repeated Ketamine Infusions for Treatment-resistant Depression

Inclusion Criteria: * Male or female Veterans aged 18 to 75 years. * Have a telephone in their home and able to hear telephone conversations. * Must meet current DSM-IV criteria for major depressive disorder (MDD), single or recurrent, without psychotic features confirmed by depression subset of the Structured Clinical Interview-Clinical Trial for DSM-IV (SCID). * Have score 32 on the Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30)for severity of major depressive episode (MDE) at screening. * Current major depressive episode resistant to treatment defined as failure to achieve improvement from at least 2 antidepressant trials of different pharmacological classes. Systematic evaluation of previous antidepressant trials will be assessed by the Antidepressant Treatment History Form (ATHF) . * If applicable, current antidepressant dosages including augmenting agents and/or frequency and duration of psychotherapy sessions must remain stable for at least 6 weeks prior to beginning of the study. Exclusion Criteria: * Inability to speak English. * Inability or unwillingness to provide written informed consent. * Moderate/severe cognitive impairment by Mini Mental State Examination (MMSE) scores 27. * Current or lifetime DSM-V criteria for post-traumatic stress disorder (PTSD), acute stress disorder, psychosis-related disorder, bipolar disorder I or II disorder, substance-induced mood disorder, any mood disorder due to a general medical condition or any Axis I disorder other than MDD as the primary presenting problem. * History of moderate or severe traumatic brain injury, Parkinson's disease, dementia of any type, multiple sclerosis, seizures or other central nervous system (CNS) related disorders. * History of comorbid substance disorder within 6 months of assessment plus positive urine toxicology screen test during baseline assessments. * Clinically unstable medical illness that could compromise the patient's ability to tolerate or likely interfere with the study procedures (e.g., history of or current myocardial ischemia or arrhythmias, congestive heart failure, severe pulmonary, renal, or hepatic disease, uncontrolled hypertension). * Current or within less than 14 days use of barbiturates or monoamine oxidase inhibitors (MAOi). * For women: pregnancy (confirmed by lab test), initiation of female hormonal treatments within 3 months of screening, or inability/ unwillingness to use a medically accepted contraceptive method during the study. * Imminent risk of suicidal/homicidal ideation and/or behavior with intent and/or plan.