Ketamine and Nitroprusside for Depression

Inclusion Criteria:

* Male or female patients, 21-65 years of age;
* Female individuals who are not of childbearing potential (i.e., surgically sterile, postmenopausal for at least one year) or using a medically accepted reliable means of contraception. Women using oral contraceptive medication for birth control must also be using a barrier contraceptive. Women of childbearing potential must also have a negative pregnancy test at screening and at pre-infusion;
* Participants must fulfill current DSM-5 criteria for Major Depression without psychotic features or Persistent Depressive Disorder with specifier of "with persistent major depressive episode";
* Depression is at least moderate severity, defined as a CGI-S score of ≥ 4;
* Current major depressive episode is of at least 4 weeks duration
* Each participant must have a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign an informed consent document
* Each participant must be able to identify a family member, physician, or friend who will act as an emergency contact

Exclusion Criteria:

* Lifetime history of psychotic features, diagnosis of schizophrenia or any other psychotic disorder, or diagnosis of bipolar disorder;
* Lifetime histories of autism, mental retardation, pervasive developmental disorders, or Tourette's syndrome;
* Current diagnosis of obsessive compulsive disorder (OCD) or eating disorder (bulimia nervosa or anorexia nervosa);
* Subjects with DSM-V drug or alcohol abuse/dependence within the preceding 2 years;
* Patients with schizotypal or antisocial personality disorder, or any clinically significant axis II disorder that would, in the investigator's judgment, preclude safe study participation;
* Patients judged clinically to be at serious and imminent suicidal or homicidal risk;
* Women who are either pregnant or nursing;
* Any serious, unstable medical illnesses including hepatic, renal impairment, gastroenterologic, respiratory, cardiovascular, endocrinologic, neurologic, immunologic, or hematologic disease;
* History of congestive heart failure or established coronary artery disease;
* History of cerebrovascular insufficiency
* History of intrapulmonary arteriovenous shunts, co-arctation of the aorta or other conditions where cardiac outflow tract is obstructed;
* Vitamin B12 deficiency;
* Clinically significant abnormal findings of laboratory parameters, physical examination, or ECG;
* Renal impairment, as reflected by a BUN \> 20 mg/dL and/or creatinin clearance of \>1.3 mg/dL;
* Thyroid impairment, as reflected by a thyroid-stimulating hormone (TSH) \> 4.2 mU/L;
* Hepatic injury, as reflected by AST or ALT greater than twice the upper limit of the reference range (AST: \>80; ALT \>110)
* Patients who have a positive urine toxicology for illicit substances at screening and within 24 hours of the infusion;
* Treatment with an irreversible MAOI within 2 weeks prior to randomization or fluoxetine within 4 weeks prior to randomization;
* Treatment with other antidepressants (classified as SSRIs, SNRIs, Atypical Antidepressants, MAOIs, TCAs) within one week of randomization.
* Previous recreational use of phencyclidine (PCP) or KET;
* Hypertension with systolic BP \>160 mm Hg or diastolic BP \>90 mm Hg at screening, systolic BP \> 165 mm Hg or diastolic BP \> 95 mm Hg immediately prior to treatment with study drug or hypotension with systolic BP \< 90 or diastolic \< 60 at screening or immediately prior to treatment with study drug; heart rate \>110 or \<60 at either of these time points;
* Treatment with sildenafil (Viagra), tadalafil (Cialis), Avanafil (Stendra), Vardenafil (Levitra) or other drugs in the same category of phosphodiesterase-5 enzyme inhibitors within 2 weeks of infusion.