Ketamine Infusion for Obsessive-Compulsive Disorder
Information source: Yale University
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Obsessive-compulsive Disorder
Intervention: ketamine (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: Yale University Official(s) and/or principal investigator(s): Michael H Bloch, MD, MS, Principal Investigator, Affiliation: Yale University
Summary
Roughly one-third of patients with obsessive-compulsive disorder (OCD) do not experience
significant clinical benefit from first-line interventions such as pharmacotherapy with
selective serotonin reuptake inhibitors (SSRI) or cognitive behavioral therapy (CBT).
Furthermore, OCD patients typically experience the full treatment benefits of first-line
interventions only after a time-lag of two to three months. Inadequate symptom relief and
delay of symptom relief from first-line treatments are sources of substantial morbidity and
decreased quality of life in OCD patients. Converging lines of evidence from neuroimaging,
genetic and pharmacological studies support the importance of glutamate abnormalities in the
pathogenesis of OCD.
The investigators are conducting an open, uncontrolled study of ketamine in
treatment-refractory OCD. Ketamine is a potent antagonist of the N-methyl-D-aspartate
(NMDA) receptor and has been demonstrated to have rapid anti-depressant effects in patients
with Major Depressive Disorder. The investigators have additionally provided evidence for
rapid improvement of comorbid OCD and trichotillomania after ketamine infusion in a
depressed woman.
Failure of symptom relief and delay of symptom relief from first-line treatments are a
source of substantial morbidity and decreased quality of life in OCD patients. Ketamine
represents the possibility to provide rapid symptom relief to OCD patients and may provide
the mechanism for future drug development to treat OCD more rapidly and effectively.
Clinical Details
Official title: Ketamine Infusion for Obsessive-Compulsive Disorder
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: OCD SeverityOCD Severity OCD Severity
Secondary outcome: Depression Symptoms
Detailed description:
Roughly one-third of patients with obsessive-compulsive disorder (OCD) fail to experience
significant clinical benefit from first-line interventions such as pharmacotherapy with
selective serotonin reuptake inhibitors (SSRI) or cognitive behavioral therapy (CBT).
Antipsychotic augmentation is the only pharmacological strategy for treatment-refractory OCD
with demonstrated efficacy in multiple double-blind trials (2). Antipsychotic augmentation
only benefits around 1 in 3 treatment-refractory OCD. Furthermore, OCD patients typically
experience the full treatment benefits of first-line interventions only after a time-lag of
two to three months. Failure of symptom relief and delay of symptom relief from first-line
treatments are sources of substantial morbidity and decreased quality of life in OCD
patients.
Converging lines of evidence from neuroimaging, genetic and pharmacological studies support
the importance of glutamate abnormalities in the pathogenesis of OCD. In Magnetic Resonance
Spectroscopy studies elevated concentrations of glutamate and related compounds have been
demonstrated in the caudate nucleus and orbitofrontal cortex of OCD patients compared to
normal controls. In genetic studies, single nucleotide polymorphisms within the glutamate
transporter gene SLC1A1 have been associated with the diagnosis of OCD. Open-label,
pharmacological treatment studies have suggested that glutamate modulating agents such as
riluzole, n-acetylcysteine and memantine may be effective in the treatment of OCD.
Ketamine is a potent antagonist of the N-methyl-D-aspartate (NMDA) receptor, a major type of
glutamate receptor in the brain. In a placebo-controlled study completed at Yale a single
dose of ketamine (0. 5 mg/kg, intravenously) had rapid antidepressant effects in depressed
patients. In these subjects ketamine infusion produced mild psychotomimetic symptoms and
euphoria that dissipated within 120 minutes, while the antidepressant effects of ketamine
infusion emerged over the first 180 minutes and persisted over 72 hours. Fifty percent of
depressed patients receiving ketamine were treatment responders at Day 3 compared to 12. 5%
in the placebo infusion group. These results have been replicated in a recent double-blind
study performed at NIMH and a third unpublished study conducted by members of our group at
Yale.
Our goal is to conduct an open-label study in treatment-refractory OCD to determine if
ketamine may be an effective acute anti-obsessional agent.
Eligibility
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. Adult between the ages of 18 and 65 years.
2. Meet DSM IV criteria for obsessive-compulsive disorder by structured clinical
interview (SCID) and have a Y-BOCS score >24.
3. Have treatment-refractory OCD. Have Y-BOCS>24 despite two SSRI trials of adequate
dose and duration and been offered prior CBT treatment.
4. Stable psychiatric medications. Subjects must have had stable doses of all
psychiatric medications for the month prior to treatment and have been on stable
doses of SSRI and clomipramine for at least 2 months prior to study enrollment.
5. Medically and neurologically healthy.
6. Able to provide written informed consent according to the Yale HIC guidelines.
Exclusion Criteria:
1. Lifetime history of substance dependence (other than nicotine and caffeine)
2. Suicide attempt or suicidal ideation requiring psychiatric hospitalization in the
previous 6 months
3. Being Pregnant
4. Known hypersensitivity to ketamine
Locations and Contacts
Connecticut Mental Health Center/ YNHH, New Haven, Connecticut 06520, United States
Additional Information
Yale OCD Research Clinic
Starting date: February 2009
Last updated: May 8, 2014
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