Clinical TrialTreatment-Resistant Depression (TRD)PlaceboKetamineKetaminePlaceboCompleted

Ketamine and Nitroprusside for Depression

Randomized, parallel-group Phase II study (n=40) comparing nitroprusside versus placebo co-administration with ketamine (0.5 mg/kg IV over 40 minutes) in patients with major depression to assess antidepressant and psychotomimetic effects.

Target Enrollment
40 participants
Study Type
Phase II interventional
Design
Randomized, triple Blind

Detailed Description

This randomized, triple-blind, parallel Phase II trial tests whether sodium nitroprusside alters the antidepressant efficacy or reduces the psychotomimetic effects of ketamine in patients with major depression.

Nitroprusside is administered as a 0.5 µg/kg/min IV infusion over 240 minutes with ketamine 0.5 mg/kg IV given during the final 40 minutes; outcomes include MADRS for mood, CADSS for psychotomimetic effects, and serial blood biomarkers to explore mechanisms.

Study Protocol

Preparation

sessions

Dosing

1 sessions
240 min each

Integration

sessions

Study Arms & Interventions

Placebo + Ketamine

inactive

Placebo saline infusion with ketamine infusion (placebo comparator).

Interventions

  • Placebo
    via IV• single dose

    Saline placebo infusion over 240 minutes (placebo), ketamine 0.5 mg/kg IV over last 40 minutes.

  • Ketamine0.5 mg/kg
    via IV• single dose• 1 doses total

    Ketamine IV infusion over 40 minutes starting at minute 200 of the 240-minute session.

Nitroprusside + Ketamine

experimental

Nitroprusside infusion with overlapping ketamine infusion (experimental).

Interventions

  • Ketamine0.5 mg/kg
    via IV• single dose• 1 doses total

    Ketamine IV infusion over 40 minutes given during final 40 minutes of nitroprusside infusion.

  • Placebo0.5 µg/kg/min
    via IV• infusion 240 min• 1 doses total

    Sodium nitroprusside infusion 0.5 µg/kg/min over 240 minutes; recorded as active comparator (encoded as placebo compound reference).

Participants

Ages
21 – 65
Sexes
Male & Female

Inclusion 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

  • 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.

Study Details

Locations

Icahn School of Medicine at Mount Sinai — New York, New York, United States

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