Clinical trial NCT00539188: N-Acetylcysteine in Adjunct to DBT for the Treatment of Self-Injurious Behavior in BPD
Official title: A Double-Blind, Placebo-controlled Pilot Study of NAC Addition to Dialectical Behavioral Therapy for the Treatment of Self-Injurious Behavior Associated With Borderline Personality Disorder
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
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
Lead sponsor: Yale University
Sponsor class: OTHER
First posted: 2007-10-04
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* Borderline Personality Disorder, as assessed by SCID-II
* A score of 10 or greater on the Self Harm Inventory (SHI) at time of evaluation
* Ability to give informed consent
* 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
* History of intolerance/allergic reaction to N-Acetylcysteine
* pregnancy, breastfeeding, or intent to become pregnant during study
* Inability to understand English
* Cognitive Impairment

Primary outcomes:
measure: Self-Harm Inventory (SHI) Score at 6 Weeks
timeFrame: 6 weeks
measure: Self-Harm Inventory (SHI) Score at Baseline
timeFrame: Baseline
Secondary outcomes:
measure: Hamilton Depression Rating Scale (HAM-D) at 6 Weeks
timeFrame: 6 weeks
measure: Hamilton Depression Rating Scale (HAM-D) at Baseline
timeFrame: Baseline
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale OCD Research Clinic
state: Connecticut
Study officials:
affiliation: Yale University
name: Christopher J Pittenger, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Coric V, Taskiran S, Pittenger C, Wasylink S, Mathalon DH, Valentine G, Saksa J, Wu YT, Gueorguieva R, Sanacora G, Malison RT, Krystal JH. Riluzole augmentation in treatment-resistant obsessive-compulsive disorder: an open-label trial. Biol Psychiatry. 2005 Sep 1;58(5):424-8. doi: 10.1016/j.biopsych.2005.04.043.
citation: Pittenger C, Krystal JH, Coric V. Glutamate-modulating drugs as novel pharmacotherapeutic agents in the treatment of obsessive-compulsive disorder. NeuroRx. 2006 Jan;3(1):69-81. doi: 10.1016/j.nurx.2005.12.006.
citation: Smith BD. Self-mutilation and pharmacotherapy. Psychiatry (Edgmont). 2005 Oct;2(10):28-37.
citation: Linehan MM (1993). The Cognitive-Behavioral Treatment of Borderline Personality Disorder. New York: The Guilford Press.
citation: Pittenger C, Bloch MH, Williams K. Glutamate abnormalities in obsessive compulsive disorder: neurobiology, pathophysiology, and treatment. Pharmacol Ther. 2011 Dec;132(3):314-32. doi: 10.1016/j.pharmthera.2011.09.006. Epub 2011 Sep 22.