Ketamine Infusion for Social Anxiety Disorder
Ketamine Infusion for Social Anxiety Disorder
-  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.
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.
Inclusion Criteria:

 1. Adult between the ages of 18 and 65 years

 2. Meet DSM IV criteria for Social Anxiety Disorder by structured clinical interview
 (SCID) and have a LSAS >60 with or without co-morbid MDD

 Exclusion Criteria:

 1. Positive pregnancy test

 2. History of substance abuse disorder within the last 6 months or positive urine
 toxicology on screening (within the previous 6 months).

 3. History of pervasive developmental disorder or psychotic disorder by DSM-IV-TR
 criteria

 4. Medical comorbidity that significantly increases the risks associated with ketamine
 infusion (e.g. untreated hypertension, significant cardiovascular disease)