Brexpiprazole in Borderline Personality Disorder

Borderline personality disorder is characterized by mood instability, cognitive symptoms,
impulsive behavior, and disturbed relationships (1-3). A variety of psychotherapies have been
developed (4-6) and, while research on the use of medication is ongoing, no drug has been
approved in the United States or elsewhere for its treatment (7). Second generation
antipsychotics have been the most intensively studied (8-11). Current treatments for BPD are
often inadequate. Dialectical behavioral therapy has been shown to reduce BPD but finding
trained psychologists is difficult.

Dysfunctions in the serotoninergic and dopaminergic systems have been demonstrated in—and
considered as possible causes for—symptoms associated with the disorder (25-28). Several
studies on the use of traditional (29) and atypical antipsychotic agents in patients with
borderline personality disorder (30-31) have shown a positive effect on individual symptoms
(29, 32-36). However, we are not aware of any study evaluating Brexpiprazole in the treatment
of patients with borderline personality disorder. In the proposed double-blind,
placebo-controlled study, the influence of Brexpiprazole on the multifaceted
psychopathological symptoms and aggression of patients with borderline personality disorder
will be investigated.

Brexpiprazole therefore has distinctive properties that make it a promising option for
patients with BPD. Brexpiprazole is a novel D2 partial agonist, has affinity for 5-HT1A, acts
as an antagonist of the noradrenergic α1/2 receptor, partial agonist for D3, and antagonist
for 5-HT2A (37-39). In addition, because of low rates of side effects, Brexpiprazole should
be a well-tolerated and in fact desired medication approach to BPD.

Inclusion Criteria:

1. Men and women age 18-65;

2. Primary diagnosis of BPD

3. Zanarini scale score of at least 9 at baseline

4. Ability to understand and sign the consent form.

Exclusion Criteria:

1. Unstable medical illness based on history or clinically significant abnormalities on
baseline physical examination

2. Subjects with schizophrenia or bipolar I disorder

3. Subjects with an active substance use disorder

4. Current pregnancy or lactation, or inadequate contraception in women of childbearing
potential

5. Subjects considered an immediate suicide risk based on the Columbia Suicide Severity
rating Scale (C-SSRS) (www.cssrs.columbia.edu/docs)

6. Illegal substance use based on urine toxicology screening

7. Initiation of psychological interventions within 3 months of screening

8. Use of any other psychotropic medication

9. Previous treatment with Brexpiprazole

10. Cognitive impairment that interferes with the capacity to understand and
self-administer medication or provide written informed consent