Ketamine as a Rapidly-Acting Antidepressant in Depressed Emergency Department Patients
Condition: Depression
MeSH terms: Emergencies; Depression
Study type: Interventional
Phase: Phase 2

Summary: 
      Investigators will conduct a trial to evaluate the use of Ketamine as an alternate treatment
      for people with Major Depressive Disorder. This study plans to explore the potential that
      Ketamine's rapid antidepressant action holds for improving outcomes in patients presenting to
      the Emergency Department with severe depression. Since this is a controlled trial we will use
      an IV of Ketamine or and equivalent volume of Diphenhydramine. Subjects will be randomly
      assigned to receive Ketamine or Benadryl. Investigators will then compare measures of mood
      pre- and post-infusion in the Emergency Department. To supplement self-reported measures of
      depressive symptoms(e.g. mood), investigators will obtain objective measures of the
      biological aspects of Major Depressive Disorder.
    

Detailed description: 
      To explore the use of ketamine as a potential rapidly-acting antidepressant (RAA) for
      Emergency Department (ED) patients with major depressive disorder (MDD).

      Investigators will conduct a randomized controlled study to evaluate the rapidity and
      persistence of antidepressant effects of a single sub-anesthetic dose of intravenous (IV)
      ketamine (0.25mg/kg) or an equivalent volume of diphenhydramine (25mg) delivered IV over 1-2
      minutes, by comparing measures of mood pre- and post-infusion in Emergency Department (ED)
      patients with MDD. Subjects will be randomly assigned (1:1) to receive a bolus of ketamine or
      diphenhydramine. To supplement self-reported measures of depressive symptoms (e.g., mood,
      suicidal ideation, etc.), investigators will obtain objective measures of heart rate and
      heart rate variability, measure serum levels of the pro- and anti-inflammatory cytokines
      (interleukin IL-1, IL-2, IL-6, IL-8, IL-10, IL-12, and tissue necrosis factor, TNF-α), which
      have been shown to play an important role in stress, depression and suicidal behavior. In
      addition, investigators will obtain serum levels of brain derived neurotrophic factor (BDNF)
      because reduced serum BDNF has been described during acute depressive episodes in patients
      with MDD, with reports of rescue effects following treatment with various antidepressants and
      with ketamine (Aydemir 2005, Gervasoni 2005, Karege 2002, Karege 2005, Duncan 2013, Shimizu
      2003). Investigators will also measure serum magnesium levels, as these have been shown to
      correlate in a predictive manner with response to conventional antidepressants (Camardese
      2012), and there are data to suggest that ketamine's efficacy in treatment-resistant
      depression could be related to a relative magnesium deficiency in such patients (Murck 2013).

      This study will allow investigators to determine to what extent low-dose ketamine, an
      N-Methyl-D-Aspartate (NMDA) antagonist, achieves a rapid reduction in symptoms for severely
      depressed ED patients with or without suicidal ideation. For decades, much higher doses of IV
      ketamine (1-2mg/kg) have been used routinely in the ED as a dissociative anesthetic (Green
      2011). In 2011, an open-label study was the first published of the use of low dose ketamine
      (0.2mg/kg), administered by rapid intravenous infusion, in the ED setting for acutely
      depressed patients which demonstrated its feasibility, safety, preliminary efficacy and
      acceptability to both ED patients and staff (Larkin 2011). One long-term goal of this
      research is to expand treatment options available to depressed ED patients that mitigate the
      need for inpatient admission and serve as a safety bridge to future out-patient treatment for
      major depression. As an adjunct to standard treatment, low-dose NMDA receptor antagonists
      have the potential to positively impact: ED waiting times; repeat visits to the ED;
      short-term risk of suicide attempts; length of stay on inpatient units and the need for
      hospital admissions for many acutely depressed patients.
    

Intervention name(s): Ketamine; Diphenhydramine
Intervention type(s): Drug; Drug
Intervention description(s): IV of Ketamine (.25mg/kg); Intravenous Diphenhydramine (25mg) at the time of presentation to Emergency Department
Other intervention name(s): Other names for ketamine: ketalar; Other names for diphenhydramine: benadryl
Intervention MeSH terms: Diphenhydramine; Promethazine; Ketamine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Ketamine; Ketlar; Depression; Antidepressants; Treatment; Acute