Ketamine for the Rapid Treatment of Major Depressive Disorder and Alcohol Use Disorder

Inclusion Criteria: * Male or female veterans and civilians, 21-65 years old * Current major depressive disorder without psychotic features by DSM-5 (antidepressant regimens can be allowed and changed during the trial) * Montgomery-Asberg Depression Rating Scale (MADRS) 20 or higher * A minimum of 4 of 11 current alcohol use disorder symptoms by DSM-5 * Heavy drinking at least 4 times in the past month ('heavy drinking' defined as 5 standard drinks per day for men and 4 standard drinks per day for women * Able to provide written informed consent Exclusion Criteria: * Current substance use disorder by DSM-5 in the past 3 months (except alcohol, tobacco, or cannabis) * Current or past history of psychotic features or psychotic disorder * Current dementia * Current uncontrolled hypertension (systolic BP \> 170 mm Hg or diastolic BP \> 100 mm Hg) * Unstable medical condition or allergy to ketamine, midazolam, naltrexone, or lorazepam---clinically determined by a physician * Imminent suicidal or homicidal risk * Pregnant or nursing women, positive pregnancy test, or inadequate birth control methods in women of childbearing potential * Positive opioid or illicit drug screen test (except marijuana) * Opioid use within 10 days prior to study medication (injectable naltrexone) or risks for opioid use during the study * Liver enzymes that are three times higher than the upper limit of normal * Current use of benzodiazepine * Acute narrow-angle glaucoma * Severe sleep apnea---clinically determined by a physician