Ketamine and Nitroprusside for Depression
Condition: Depression
MeSH terms: Depression; Depressive Disorder
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      Ketamine is an effective fast-acting therapeutic intervention for patients with treatment
      refractory depression that is known to have the unwanted effect of inducing temporary
      psychotomimetic symptoms (i.e., delusions, hallucinations and thought disorganization) in
      some patients. The precise mechanisms of these psychotropic effects remain to be elucidated,
      but for several decades the NMDA-type glutamate receptor has been hypothesized to be of
      central importance. In this vain, recent studies of the antihypertensive agent nitroprusside
      - which increases the availability of the molecular nitric oxide, a known by-product of NMDA
      activity - have found evidence for antipsychotic properties both in humans with psychotic
      illness and healthy subjects given ketamine. Here, the clinical team proposes a study that
      will build on this work by evaluate the effects of nitroprusside on both the antidepressant
      and psychotomimetic effects of ketamine given to patients to treat refractory depression. In
      addition, as an exploratory aim, by collecting serial blood samples from the subjects, as the
      subjects are administered ketamine and nitroprusside, the clinical team will seek to
      determine functional markers of therapeutic effect and the mechanisms by which ketamine
      modulates both mood and psychotic states Research Question: The clinical team will test
      whether the effects of ketamine (KET) on mood and psychotic states is modified by
      co-administration with sodium nitroprusside (NP) in patients with depression. Furthermore,
      the clinical team will evaluate the extent to which the underlying biology of disease states
      and drug mechanisms can be inferred through analysis of brain-derived molecular material
      isolated from the peripheral circulation.

      Specific Aims:

      Aim I. To test whether co-administration with NP has any impact on the efficacy of KET as an
      antidepressant.

      Aim II: To test the ability of NP to prevent the psychotomimetic effects of KET in patients
      with depression.

      Research Hypotheses:

      Research Hypothesis I. Patients pre-treated with NP will experience attenuated antidepressant
      effects (measured by MADRS score) following KET compared to pre-treatment with placebo.

      Research Hypothesis II: Patients pre-treated with NP will experience attenuated
      psychotomimetic effects (e.g., CADSS score) immediately following KET compared to
      pre-treatment with placebo.
    

Intervention name(s): Placebos; Ketamine; Nitroprusside
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Placebo saline; 0.5 mg/kg ketamine; 0.5 mcg/kg nitroprusside
Intervention MeSH terms: Nitroprusside; Ketamine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: depression; ketamine; nitroprusside