Ketamine Infusion for Social Anxiety Disorder
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Anxiety, Healthy Studies, Psychiatric |
| Therapuetic Areas: | Psychiatry / Psychology, Other |
| Healthy: | No |
| Age Range: | 18 - 65 |
| Updated: | 7/13/2016 |
| Start Date: | March 2014 |
| End Date: | March 2018 |
- 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.
- 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.
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)
We found this trial at
1
site
New Haven, Connecticut 06508
Principal Investigator: Michael H. Bloch, MD, MS
Phone: 203-737-4809
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