Ketamine and Nitroprusside for Depression
Condition: Depression
MeSH terms: Depression; Depressive Disorder
Intervention: Placebos; Ketamine; Nitroprusside
Intervention description: Placebo saline; 0.5 mg/kg ketamine; 0.5 mcg/kg nitroprusside
Intervention MeSH terms: Nitroprusside; Ketamine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking description: Both participants and research staff (aside from pharmacy) will be blinded
Enrollment: 40.0
Sex: All
Minimum age: 21 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: depression; ketamine; nitroprusside

Summary:

      The purpose of this study is to test the effects of the medication ketamine and the
      medication called nitroprusside in patients with major depression. Ketamine has both good and
      bad effects. Some studies have shown that ketamine improves depression. However, studies have
      also shown that it causes strange and sometimes unpleasant sensations referred to "psychotic"
      or "dissociative" symptoms. An example of a psychotic symptom would be hearing or seeing
      something that in reality is not there. The study team would like to see if nitroprusside can
      prevent the reported bad effects of ketamine without blocking the reported good effects. This
      might make ketamine a better treatment for depression.
    

Eligibility criteria:

        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.