Ketamine Infusion for Obsessive-Compulsive Disorder

This study has been completed.
Sponsor:
Collaborator:
National Alliance for Research on Schizophrenia and Depression
Information provided by (Responsible Party):
Michael Bloch, Yale University
ClinicalTrials.gov Identifier:
NCT01349231
First received: April 9, 2011
Last updated: October 3, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Obsessive-compulsive Disorder
Drug: ketamine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Ketamine Infusion for Obsessive-Compulsive Disorder

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • OCD Severity [ Time Frame: 1 day after ketamine infusion ] [ Designated as safety issue: No ]
    We will examine change from baseline in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) ratings of OCD severity at 1 day following infusion.

  • OCD Severity [ Time Frame: 2 days following infusion ] [ Designated as safety issue: No ]
    We will examine change from baseline in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) ratings of OCD severity at 2 days following infusion.

  • OCD Severity [ Time Frame: 3 days following infusion ] [ Designated as safety issue: No ]
    We will examine change from baseline in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) ratings of OCD severity at 3 days following infusion.

  • OCD Severity [ Time Frame: 5 days following infusion ] [ Designated as safety issue: No ]
    We will examine change from baseline in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) ratings of OCD severity at 5 days following infusion.

  • OCD Severity [ Time Frame: 7 days following infusion ] [ Designated as safety issue: No ]
    We will examine change from baseline in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) ratings of OCD severity at 7 days following infusion.

  • OCD Severity [ Time Frame: 14 days following infusion ] [ Designated as safety issue: No ]
    We will examine change from baseline in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) ratings of OCD severity at 14 days following infusion.

  • OCD Severity [ Time Frame: 21 days following infusion ] [ Designated as safety issue: No ]
    We will examine change from baseline in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) ratings of OCD severity at 21 days following infusion.

  • OCD Severity [ Time Frame: 28 days following infusion ] [ Designated as safety issue: No ]
    We will examine change from baseline in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) ratings of OCD severity at 28 days following infusion.


Secondary Outcome Measures:
  • Depression Symptoms [ Time Frame: First 4 weeks following infusion ] [ Designated as safety issue: No ]
    We will examine Hailton Rating Scale for Depression (HRDS) ratings of depression severity at 1,2 and 3 hours and 1,2,3,5,7,14,21 and 28 days following a single ketamine infusion. We will examine change from baseline in depression severity at 1-3 days following infusion.


Enrollment: 10
Study Start Date: February 2009
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ketamine
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.
Drug: ketamine
Ketamine (a single 0.5mg intravenously over 40 minutes).

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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01349231

Locations
United States, Connecticut
Connecticut Mental Health Center/ YNHH
New Haven, Connecticut, United States, 06520
Sponsors and Collaborators
Yale University
National Alliance for Research on Schizophrenia and Depression
Investigators
Principal Investigator: Michael H Bloch, MD, MS Yale University
  More Information

Additional Information:
No publications provided by Yale University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Michael Bloch, Assistant Professor, Yale University
ClinicalTrials.gov Identifier: NCT01349231     History of Changes
Other Study ID Numbers: 0901004660
Study First Received: April 9, 2011
Last Updated: October 3, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Yale University:
obsessive-compulsive disorder
ketamine
glutamate

Additional relevant MeSH terms:
Obsessive-Compulsive Disorder
Compulsive Personality Disorder
Anxiety Disorders
Mental Disorders
Personality Disorders
Ketamine
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Analgesics
Sensory System Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on April 15, 2014