Rapid Antidepressant Effects of Ketamine in Major Depression
Condition: Depression; Mood Disorders; Major Depresssion
MeSH terms: Depression; Depressive Disorder; Mood Disorders
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Depressive disorders may be severe, chronic and often life-threatening illnesses. Impairment
      in physical and social functioning resulting from depression can be just as severe as other
      chronic medical illnesses. Recent preclinical and clinical studies suggest that the
      glutamatergic system is involved in the mechanism of action of antidepressants.

      This study examines whether ketamine can cause a rapid-next day antidepressant effect in
      patients with Major Depressive Disorder.

      This study was designed to address the questions:

      Does the NMDA antagonist ketamine produce rapid antidepressant effects in patients with
      treatment-resistant major depression? What are the neurobiological correlates of
      antidepressant response (examining multi-modal MRI, MEG, polysomnography and serum markers)
      Patients, ages 18 to 65 years with treatment-resistant major (unipolar) depression will in a
      double-blind crossover study receive either intravenous ketamine or saline solution.
    

Detailed description: 
      This study will test whether a single dose of ketamine - a drug that blocks a brain receptor
      called NMDA - can cause a rapid (next day) antidepressant effect in patients with major
      depression. Several medications are effective for treating depression; however, they take
      weeks or months to achieve their full effects. A more rapidly acting antidepressant would
      have a significant impact on the treatment of depression. In a previous study, ketamine
      produced a rapid antidepressant effect within hours, but the effect lasted less than 1 week.
      Understanding how ketamine works may lead to a better understanding of the causes of
      depression and the design of a longer lasting rapidly acting antidepressant.

      Patients between 18 and 65 years of age who are currently experiencing an episode of major
      depression of at least 4 weeks duration and have not responded to two treatment trials may be
      eligible for this study. Candidates are screened with a medical and psychiatric history,
      physical examination, and blood and urine tests.

      Participants undergo the following tests and procedures:

      Medication tapering: Patients who are taking medications for depression are tapered off the
      drugs over a 1- to 2-week period.

      Ketamine/placebo trial: Patients are given a single dose of either ketamine or placebo (an
      inactive substance), administered intravenously (through a vein) over 40 minutes. After 7
      days, patients are given another dose of study drug in crossover fashion; that is, those who
      previously took ketamine are switched to receive placebo, and those who took placebo are
      switched to ketamine. Oximetry (measurement of blood oxygen), pulse, and blood pressure are
      measured continuously for 1 hour before and 4 hours after each ketamine or placebo dose to
      monitor safety.

      Interviews and rating scales: Patients complete a series of psychiatric rating scales to
      assess the effects of the study drug on mood and thinking. The rating scales are repeated up
      to 18 times during the study, with each time taking about 15 to 20 minutes.

      Physical examination and laboratory tests: Patients have a physical examination, blood tests,
      weight measure, and electrocardiogram (ECG) at the beginning and end of the study. They will
      also have multi-modal MRI, MEG, polysomnography and serum marker studies.

      The primary endpoint will be the change in clinical ratings of depression. Secondary
      endpoints will examine neurobiological correlates (i.e., multi-modal MRI, MEG,
      polysomnography and serum markers) of antidepressant response to ketamine (compared to
      placebo).
    

Intervention name(s): Ketamine; Placebo
Intervention type(s): Drug; Drug
Intervention MeSH terms: Ketamine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Other
Keywords: Depression; NMDA Antagonist; Treatment Resistant; Glutamatergic System; Major Depression