N-Acetylcysteine Augmentation in Treatment-Refractory Obsessive-Compulsive Disorder
Condition: Obsessive-Compulsive Disorder
MeSH terms: Compulsive Personality Disorder; Obsessive-Compulsive Disorder
Intervention: N-Acetylcysteine; placebo
Intervention description: 3000 mg by mouth PO (1200 mg AM, 1800 mg PM), 12 weeks; placebo, 2 capsules PO AM, 3 capsules PO PM, 12 weeks
Intervention MeSH terms: Acetylcysteine; N-monoacetylcystine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: obsessive-compulsive disorder; OCD; glutamate; N-Acetylcysteine; augmentation

Summary:

      Obsessive-compulsive disorder (OCD) affects 2-3% of the population and leads to a great deal
      of suffering. Many patients benefit from established treatments, the mainstay of which are
      cognitive behavioral therapy and a group of antidepressant medications known as serotonin
      reuptake inhibitors. However, 20-30% of patients get minimal benefit from these established
      therapeutic strategies. New avenues of treatment are urgently needed.

      Existing medications for obsessive-compulsive disorder affect the neurotransmitters serotonin
      or dopamine; but increasing evidence suggests that functional disruptions of a different
      neurotransmitter, glutamate, may contribute to some cases of OCD. The researchers are
      therefore interested in using medications that target glutamate as novel treatment options
      for those OCD patients who do not benefit from established treatments.

      One such medication is the drug N-Acetylcysteine, whose glutamatergic antagonistic properties
      may be effective in reducing the glutamatergic hyperactivity that is thought to contribute to
      the pathophysiology of OCD and major depressive disorder (MDD).

      Riluzole, which is FDA approved for amyotrophic lateral sclerosis (ALS, or Lou Gehrig's
      disease) is also a glutamatergic agent. There is evidence that riluzole possesses
      anti-depressant, anti-obsessional, and anti-anxiety properties.

      The modulation of glutamatergic activity is a promising new approach to the treatment of mood
      disorders. The researchers are therefore now recruiting patients to participate in a
      double-blind, placebo-controlled trial of N-Acetylcysteine, added to whatever other OCD
      medications they are taking.
    

Eligibility criteria:

        Inclusion Criteria:

          -  DSM-IV diagnosis of OCD, confirmed by SCID-IV; symptoms of at least 1 year duration

          -  moderate to severe OCD symptoms (Y-BOCS > 16)

          -  documented failure of an adequate trial of an SSRI

          -  agreement to engage in a reliable form of birth control (women only)

        Exclusion Criteria:

          -  primary diagnosis of a psychotic disorder

          -  active substance abuse or dependence

          -  unstable medical condition

          -  prior exposure to N-Acetylcysteine

          -  prior psychosurgery

          -  pregnancy, breastfeeding, or intent to become pregnant during study

          -  liver function tests (LFTs) elevated to more than 2x the upper limit of normal

          -  evidence of active liver disease

          -  seizure disorder

          -  active suicidal ideation