Ketamine Infusion for Obsessive-Compulsive Disorder
Condition: Obsessive-compulsive Disorder
MeSH terms: Compulsive Personality Disorder; Obsessive-Compulsive Disorder
Study type: Interventional
Phase: Phase 2

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.
    

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.
    

Intervention name(s): ketamine
Intervention type(s): Drug
Intervention description(s): Ketamine (a single 0.5mg intravenously over 40 minutes).
Intervention MeSH terms: Ketamine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: obsessive-compulsive disorder; ketamine; glutamate