Ketamine in the Treatment of Depression
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Study type: Interventional
Phase: Phase 2

Summary: 
      Depressed patients will be offered experimental treatment with a new, potentially fast-acting
      antidepressant called ketamine while being scanned by magnetic resonance imaging (MRI) to
      measure the chemical effect of the drug. Ketamine will be given in a dose of 0.0 (placebo),
      0.1, 0.2, 0.3, 0.4, or 0.5 mg/kg. If a patient does not respond to ketamine after the first
      infusion, it may be because s/he received ketamine placebo or the dose of ketamine was too
      low. In that case, an optional second scan and infusion of active ketamine (0.5 mg/kg) will
      be offered. This second scan will occur no later than weeks after the first scan/infusion (as
      scheduling permits). There is no guarantee that the patient will respond to the second
      ketamine infusion. Patients enrolled in the study are eligible for up to 6 months treatment
      with their study psychiatrist after the ketamine infusion(s).

      Healthy Volunteers: Healthy controls will receive an infusion of ketamine at a single dose
      (0.5 mg/kg). Volunteers will only receive one MRI scan and infusion.
    

Detailed description: 
      Major depressive disorder (MDD) is a common illness, affecting over 14 million American
      adults each year. MDD is a leading cause of disability worldwide, and is responsible for huge
      workplace and healthcare costs. The several week delay between onset of treatment and
      improvement in MDD symptoms with currently available treatments further increases the burden
      of the disorder. Shortening this delay is a major unmet challenge in the treatment of MDD.
      Studies report that a single intravenous low dose of a drug called ketamine can bring about
      substantial improvement in depression in hours, even in patients that have not improved with
      other antidepressant treatments. Certain aspects of ketamine's drug action are fairly well
      understood, but the question remains of how these properties relate to antidepressant effect.
      The investigator's preliminary data support the rapid antidepressant benefit from ketamine.
      The investigators have used a scanner to measure the effects of ketamine on two major brain
      chemical transmitters and found that it causes a significant increase (more than 60%) in
      glutamate (Glu) and gamma aminobutyric acid (GABA) levels in the front of the brain. The
      investigators hypothesize that this increase in Glu and GABA levels, is responsible for the
      antidepressant action of the medication. Knowing how ketamine works could help to develop
      better medications that can be used orally and used for maintenance of the improvement seen
      with ketamine. The objective of the proposed dose finding study is to examine the
      relationship between the ketamine-induced improvement of MDD and the Glu and GABA responses
      to ketamine and to compare the Glu and GABA responses to ketamine in MDD and healthy subjects
      to better understand the pathophysiology of MDD. To achieve these aims this the investigators
      propose a randomized, placebo-controlled, double blind study with several different doses of
      ketamine. The investigators will conduct MRI scans to measure Glu and GABA before and during
      the ketamine treatment.
    

Intervention name(s): Ketamine; Saline; Magnetic Resonance Imaging (MRI)
Intervention type(s): Drug; Drug; Procedure
Intervention description(s): Single dose of 0.1, 0.2, 0.3, 0.4 or 0.5 mg/kg of ketamine given intravenously over 40 minutes.; Single infusion of saline given intravenously over 40 minutes.; 90-minute scan during the 40-minute infusion.
Other intervention name(s): Ketalar; Saline solution
Intervention MeSH terms: Ketamine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Ketamine; Major Depressive Disorder; Treatment; Depression