This trial is active, not recruiting.

Condition social anxiety disorder
Treatments ketamine, saline
Phase phase 0
Sponsor Yale University
Collaborator Patterson Trust Awards Program in Clinical Research
Start date March 2014
End date March 2018
Trial size 18 participants
Trial identifier NCT02083926, 1310012947


- 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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model crossover assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Ketamine will be given at a dose of 0.5mg/kg over 40 minutes. This dose is identical to that used in previous anti-depressant studies of Ketamine.
Ketamine (a single 0.5mg/kg intravenously over 40 minutes).
(Placebo Comparator)
Saline will be given at a dose of 0.5 mg/kg over a 40 minute period.
Saline (a single 0.5mg/kg intravenously over 40 minutes).

Primary Outcomes

Visual Analog Scale (VAS) of Anxiety States
time frame: First 2 weeks following infusion

Secondary Outcomes

Anxiety Severity
time frame: First 2 weeks following infusion
Depression Severity
time frame: First 2weeks following infusion
Clinical Global Impressions
time frame: First 2 weeks following infusion
Brief Psychiatric Rating Scale, Positive Symptom Subscale (BPRS-PS)
time frame: First 2 weeks following infusion
Clinician-Administered Dissociative States Scale
time frame: First 2 weeks following infusion
Self-Statement During Public Speaking Scale (SPSS)
time frame: First week following infusion
Impromptu Speech Behavioral Assessment Test
time frame: First 2 weeks following infusion
Attention Bias
time frame: First 2 weeks following infusion
SAD Severity
time frame: First 2 weeks following infusion
Positive and Negative Affect Symptoms
time frame: First Week following infusion
State-Trait Anxiety Inventory
time frame: First 2 Weeks Following Infusion

Eligibility Criteria

Male or female participants from 18 years up to 65 years old.

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)

Additional Information

Official title Ketamine Infusion for Social Anxiety Disorder
Principal investigator Michael H. Bloch, MD, MS
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.
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by Yale University.