Ketamine Infusion for Social Anxiety Disorder
Condition: Social Anxiety Disorder
MeSH terms: Anxiety Disorders; Phobia, Social
Study type: Interventional
Phase: Early Phase 1

Summary: 
      -  Social Anxiety Disorder (SAD) is common and causes significant impairment.

        -  First-line treatments for Social Anxiety Disorder are only partially effective. Many SAD
           patients experience little or inadequate symptom relief with available treatments.

        -  Ketamine is a potent NMDA receptor antagonist. Ketamine represents an agent with a
           potentially novel mechanism of action for the treatment of anxiety disorders.

        -  Ketamine has demonstrated efficacy in the treatment of psychiatric disorders closely
           related to Social Anxiety Disorder including Major Depression, Bipolar Depression and
           possibly Obsessive-Compulsive Disorder.

      Ketamine represents the possibility to provide rapid symptom relief to patients with SAD and
      may provide the mechanism for future drug development to treat SAD more rapidly and
      effectively.
    

Detailed description: 
      Roughly one-third to one-half of patients with generalized SAD do not experience significant
      clinical benefit from current evidence-based treatment for SAD such as pharmacotherapy with
      selective serotonin reuptake inhibitors (SSRI) or venlafaxine and cognitive behavioral
      therapy (CBT). Failure of anxiety relief in patients with SAD is a source of substantial
      morbidity, distress, and decreases in quality of life. Novel pharmacological treatments are
      needed to improve patient outcomes with SAD.

      Converging lines of evidence from neuroimaging and pharmacological studies support the
      importance of glutamate abnormalities in the pathogenesis of SAD. In a Magnetic Resonance
      Spectroscopy (MRS) study, an elevated glutamate to creatinine ratio was found in the anterior
      cingulate cortex of SAD patients when compared to healthy controls. Elevated thalamic
      glutamine levels have been demonstrated in patients with SAD. Pre-clinical rodent studies
      have also established a strong link between glutamate regulation and anxiety.

      Ketamine is a potent antagonist of the N-methyl-D-aspartate (NMDA) receptor, a major type of
      glutamate receptor in the brain. Ketamine is routinely used for anesthetic induction because
      of its dissociative properties. However in research studies, ketamine is effective treatment
      in reducing symptoms in depressive and possibly anxiety disorders. In multiple controlled
      clinical studies, ketamine has produced a rapid antidepressant effect in unipolar and bipolar
      depression. Ketamine's anti-depressant effects peak 1-3 days following infusion. Ketamine's
      antidepressant effect is observed long after ketamine has been metabolized and excreted by
      the body and after ketamine's sedative and dissociative effects have dissipated.

      The results of several clinical studies suggest that ketamine may also have significant
      anxiolytic effects. Patients with major depressive disorder given a single ketamine infusion
      have shown strong and significant reductions in comorbid anxiety symptoms. A trial including
      11 depressed patients demonstrated a significant reduction in anxiety symptoms (Hamilton
      Anxiety Rating Scale (HAM-A)) following ketamine infusion. This improvement is supported by
      one of the earlier placebo-controlled trials of ketamine which demonstrated that the psychic
      anxiety item was one of 4 (out of 21) items on the Hamilton Depression Rating Scale (HAM-D)
      demonstrating significant improvement after ketamine infusion.

      The investigators goal is to conduct a randomized, placebo-controlled crossover study to
      explore the efficacy and time course of action of intravenous ketamine in the treatment of
      SAD.
    

Intervention name(s): Ketamine; Saline
Intervention type(s): Drug; Other
Intervention description(s): Ketamine (a single 0.5mg/kg intravenously over 40 minutes).; Saline (a single 0.5mg/kg intravenously over 40 minutes).
Other intervention name(s): Ketalar; Placebo
Intervention MeSH terms: Ketamine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Social Anxiety Disorder; SAD; Ketamine