Clinical trial NCT00539188
Conditions: Borderline Personality Disorder Self-Injurious Behavior
Keywords: Borderline Personality Disorder(BPD) Dialectical Behavioral Therapy (DBT) glutamate N-Acetylcysteine Borderline Personality Disorder with Self-Injurious Behavior
Sponsor: Yale University
Start date: 2007-09-01; Completion date: 2010-11-01
Enrollment: 6 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Self-Injurious Behavior (SIB) is a dangerous and common symptom in Borderline Personality Disorder (BPD) patients. Approximately 70% of patients with BPD engage in SIB at some point, compared to 17.5% of patients with other personality disorders. While SIB may prompt unnecessary psychiatric hospitalizations, it may also cause potential underestimation of the lethality of suicidal behavior, thus creating a major and confusing challenge in the practice of clinical psychiatry.

Dialectical Behavioral Therapy (DBT) is a collection of therapeutic techniques focused on emotional regulation, impulse control, and improving safety in patients with BPD and others with marked self-destructive behavioral tendencies. Though DBT has marked ability to reduce BPD symptomatology, including SIB, improvement in SIB is limited and dependent on extensive therapy and time.

Furthermore, the literature on the pharmacological treatment of SIB associated with BPD is scarce. Animal studies suggest that SIB may be associated with an imbalance between dopamine and glutamate in the brain. Anti-seizure medications that modulate glutamate transmission, such as lamotrigine and topiramate, have been suggested to be effective in the treatment of SIB in humans.

Preliminary evidence suggests that antiglutamatergic medications may decrease SIB in patients with BPD. Early studies have focused on the antiglutamatergic drug riluzole. More recently, we have become interested in the amino acid N-acetylcysteine (NAC), which is used clinically for its antioxidant properties and is widely available as a nutritional supplement. Recent animal studies have suggested that NAC can modulate glutamate in the central nervous system in a way very similar to that proposed for riluzole, and indeed we have observed NAC to have an effect similar to riluzole in a case of treatment-refractory obsessive-compulsive disorder.

This study will be a double-blind, randomized, and placebo-controlled evaluation of N-Acetylcysteine as an adjunct to DBT in the treatment of SIB associated with BPD. Subjects participating in this study will be recruited exclusively from the Dialectical Behavioral Therapy program of the Yale-New Haven Hospital, in order to maximize homogeneity of the psychotherapeutic care received during their participation.

Detailed description:
Investigators have withdrawn study due to poor subject compliance. After 3 consecutive participants were either unable to complete all 6 weeks of the study or dropped out of the DBT program, a decision was reached to discontinue recruitment and study was terminated.

Arms: arm 1: Patients randomized to this arm will receive N-Acetylcysteine augmentation, at a standard dose (3000 mg daily), in addition to the medication regimen they are on at enrollment arm 2: 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.
Interventions: intervention 1: N-Acetylcysteine intervention 2: placebo
Intervention descriptions: intervention 1: 3000 mg PO (1200 mg AM, 1800 mg PM), 6 weeks intervention 2: placebo, 2 capsules PO AM, 3 capsules PO PM, 6 weeks

Protocol documents: