Ketamine Infusion for Obsessive-Compulsive Disorder

Obsessive-compulsive Disorder Clinical Trial

Official title:

Ketamine Infusion for Obsessive-Compulsive Disorder

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01349231
• Other study ID #: 0901004660
• Status: Completed
• Phase: Phase 2
• First received: April 9, 2011
• Last updated: May 8, 2014
• Start date: February 2009
• Est. completion date: December 2011

Study information

• Verified date: May 2014
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Compulsive Behavior
• Obsessive-Compulsive Disorder

Intervention

Drug:
• ketamine
Ketamine (a single 0.5mg intravenously over 40 minutes).

Locations

Country	Name	City	State
United States	Connecticut Mental Health Center/ YNHH	New Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Yale University	National Alliance for Research on Schizophrenia and Depression

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	OCD Severity	We will examine change from baseline in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) ratings of OCD severity at 1 day following infusion. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) assesses obsessive and compulsive symptom severity. Obsessions are rated on a scale from 0-20 and compulsions are rated on a scale of 0-20, for a total scale of 0-40. Scores on the obsessions scale and scores on the compulsions scale are summed to obtain the total score. The higher the score, the more severe the OCD.	Baseline and 1 day after ketamine infusion	No
Primary	OCD Severity	We will examine change from baseline in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) ratings of OCD severity at 2 days following infusion. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) assesses obsessive and compulsive symptom severity. Obsessions are rated on a scale from 0-20 and compulsions are rated on a scale of 0-20, for a total scale of 0-40. Scores on the obsessions scale and scores on the compulsions scale are summed to obtain the total score. The higher the score, the more severe the OCD.	Baseline and 2 days following infusion	No
Primary	OCD Severity	We will examine change from baseline in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) ratings of OCD severity at 3 days following infusion. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) assesses obsessive and compulsive symptom severity. Obsessions are rated on a scale from 0-20 and compulsions are rated on a scale of 0-20, for a total scale of 0-40. Scores on the obsessions scale and scores on the compulsions scale are summed to obtain the total score. The higher the score, the more severe the OCD.	Baseline and 3 days following infusion	No
Secondary	Depression Symptoms	We will examine change from baseline in Hamilton Rating Scale for Depression (HRDS) ratings of depression severity at day 1-3 following a single ketamine infusion. The HRDS assesses severity of, and change in, depressive symptoms. The HRDS is a 21 item scale with scores ranging from 0-66. The higher the score, the more severe the depression.	Baseline, Day 1, Day 2, and Day 3	No

External Links

•   Yale OCD Research Clinic