Ketamine for Depression and Alcohol Dependence
Condition: Depression; Alcohol Dependence
MeSH terms: Alcoholism; Depression; Depressive Disorder
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to evaluate the efficacy of ketamine in reducing depressive
      symptoms in subjects with a comorbid major depressive episode and alcohol dependence. The
      investigators hypothesize the following for the present study:

      A single dose of ketamine will induce a rapid, robust and sustained reduction in depressive
      symptoms in subjects with a comorbid major depressive episode and alcohol dependence relative
      to placebo as defined by change in Hamilton Depression Rating Scale total scores at 72 hours
      post infusion.

      A single dose of ketamine can be delivered safely, with minimal adverse events or
      complications, in subjects with a comorbid major depressive episode and alcohol dependence.
    

Detailed description: 
      Major depression and alcohol dependence are both within the ten disorders for highest
      worldwide disease burden as identified by the World Health Organization (WHO), and these
      disorders frequently co-occur, especially in high-service utilizing patients with severe and
      persistent mental illness. Currently available treatments are inadequate for both chronic
      conditions alone, and the inadequacy is even clearer in people meeting criteria for both
      disorders. Ketamine was first reported as a rapidly-acting antidepressant in 2000 via
      research occurring at Yale, and, since that time, in several small randomized controlled
      trials, a single subanesthetic dose of intravenous ketamine has demonstrated efficacy in
      improving mood in unipolar and bipolar depression within only hours after administration.
      These effects can last at least a week. Interestingly, ketamine has been demonstrated to
      produce a more robust effect in treatment-refractory unipolar depressed subjects with a
      family history of alcoholism relative to similarly difficult-to-treat subjects without a
      family history of alcohol problems. In addition, recently-detoxified alcoholics have been
      safely administered subanesthetic doses of ketamine, and, during these infusions, alcoholics
      (and even those with only a family history of alcoholism) displayed a differential response
      to ketamine, e.g. blunted psychotic-like and cognitive effects, relative to healthy controls.
      Therefore, ketamine may reduce depressive symptoms and alcohol consumption compared to
      placebo in patients with comorbid major depression and current alcohol dependence. Positive
      results will mark a major advance in the clinical care of those being treated for both
      conditions and will open the door for further scientific investigations into the clinical
      neuroscience of these highly comorbid and prevalent conditions.

      This is a two phase, double-blind, randomized, placebo-controlled, cross-over,
      proof-of-concept study designed to determine the effects of a single dose of ketamine,
      administered IV, on mood and alcohol consumption, in psychotropic medication-free patients
      meeting DSM-IV-TR criteria for a major depressive episode (MDE) and current alcohol
      dependence. Participants will be assigned randomly to receive either intravenous ketamine
      (0.5mg/kg) or saline solution 2 weeks apart in a cross over design. The ketamine dose was
      based on previous studies in patients with depression and bipolar disorder. A team member
      experienced with ketamine infusions will administer the study medication over a 40-minute
      infusion in a blinded fashion at the Biological Studies Unit at the WHVA.

      20 depressed alcohol dependent subjects between the ages of 21-65 will be recruited for this
      study through advertising and the West Haven VA clinics. Subjects will complete an informed
      consent process and will be thoroughly screened for inclusion and exclusion criteria as
      described below. Individuals will be given a post consent test to evaluate their
      understanding of the procedure. For subjects who provide incorrect answers to any of the test
      items, the research staff will review the correct answers with the subject and show the
      subject where the correct answers are found in the consent form. Those who get more than 60%
      of the questions wrong and are still unable to understand the procedure after reviewing it
      with the research staff will be excluded from the study. They will be referred to appropriate
      resources for outpatient treatment of their depression and alcoholism. Before start of the
      study all patients will be free of any psychotropic medications.
    

Intervention name(s): Ketalar (ketamine)
Intervention type(s): Drug
Intervention description(s): Intravenous Ketamine 0.5mg/kg
Intervention MeSH terms: Ketamine
Intervention model: Single Group Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: depression; alcohol; comorbidity; ketamine; glutamate; NMDA