N-Acetylcysteine Augmentation in Treatment-Refractory Obsessive-Compulsive Disorder

Yale University

Status and phase: Terminated; Phase 2

Conditions: Obsessive-Compulsive Disorder

Treatments: Drug: placebo; Drug: N-Acetylcysteine

Study type: Interventional

Funder types: Other

Identifiers

NCT00539513

0603001215

Details and patient eligibility

About

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.

Full description

Due to limited participation, this study has closed.

Enrollment: 10 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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10 participants in 2 patient groups, including a placebo group

N-Acetylcysteine

Experimental group

Description:

Patients randomized to this arm will receive N-Acetylcysteine augmentation, at a standard dose titrated to 3000 mg within the first week, in addition to the medication regimen they are on at enrollment

Treatment:

Drug: N-Acetylcysteine

placebo

Placebo Comparator group

Description:

Patients randomized to this arm will receive placebo, formulated to be indistinguishable from N-Acetylcysteine, in addition to the medication regimen they are on at study enrollment.

Treatment:

Drug: placebo