Seroquel Extended Release (XR) for the Management of Borderline Personality Disorder (BPD)

The secondary objectives in this study are aimed at answering further questions regarding
symptom assessments, dosing strategies, and safety. The specific secondary objectives are
listed below:

1. Response rate: In previous studies using the ZAN-BPD, response was defined as a 50%
reduction of ZAN-BPD scores. Response rates will be compared between Seroquel XR and
placebo.

2. Other Symptom Measures: Over the last twenty years, other rating scales of a general
nature have been used to assess BPD patients in clinical trials. To fully assess the
patients as they progress through the study, the following scales will be administered:
Symptom Checklist 90 - Revised (SCL-90 R), Montgomery Asberg Depression Rating Scale
(MADRS), Barratt Impulsivity Scale (BIS), Schedule for Interviewing Borderlines (SIB),
Overt Aggression Scale - Modified (OAS-M), Young Mania Rating Scale (YMRS), the
Borderline Evaluation of Severity over Time (BEST), and the Global Assessment of
Function (GAF).

3. Side-Effects: To be able to report the safety of Seroquel XR for BPD, a combination of
objective and subjective measures will be employed. Objectively, weight, height (and
BMI), prolactin, glucose, cholesterol and triglycerides will be assessed at baseline
and endpoint. Objective ratings of movement side effects will be performed using
Simpson Angus Scale (SAS) (Simpson and Angus 1970), Barnes Akathisia Scale (BAS)
(Barnes 1989), and Abnormal Involuntary Movement Scale (AIMS) (Guy 1976), and at
baseline and endpoint. Regarding possible side effects reported by patients, their
reports of headache, somnolence, and other experiences will be tabulated.

Secondary objective data will be analyzed as continuous variable data over the time of the
study or, when appropriate, comparisons of baseline to endpoint will be made.

Inclusion Criteria:

- Consent

- A diagnosis of borderline personality disorder (301.83)

- All subjects will have a ZAN-BPD greater or equal to 9 at randomization.

- Males and females aged 18-45 years

- Female patients of childbearing potential must be using a reliable method of
contraception and have a negative urine human chorionic gonadotropin (HCG) test at
enrollment

- Able to understand and comply with the requirements of the study

Exclusion Criteria:

- Pregnancy or lactation

- Any DSM-IV Axis I disorder not defined in the inclusion criteria. The patients with
BPD may not have bipolar I disorder, schizophrenia, schizoaffective disorder,
delirium, or dementia. Neither may they have current DSM-IV substance dependence.

- Patients who, in the opinion of the investigator, pose an imminent risk of suicide or
a danger to self or others

- Known intolerance or lack of response to quetiapine fumarate, as judged by the
investigator

- Use of any of the following cytochrome P450 3A4 inhibitors in the 14 days preceding
enrollment including but not limited to: ketoconazole, itraconazole, fluconazole,
erythromycin, clarithromycin, troleandomycin, indinavir, nelfinavir, ritonavir,
fluvoxamine, and saquinavir

- Use of any of the following cytochrome P450 inducers in the 14 days preceding
enrollment including but not limited to: phenytoin, carbamazepine, barbiturates,
rifampin, St. John's Wort, and glucocorticoids

- Administration of a depot antipsychotic injection within one dosing interval (for the
depot) before randomization

- Substance or alcohol dependence at enrollment (except dependence in full remission,
and except for caffeine or nicotine dependence), as defined by DSM-IV criteria

- Opiates, amphetamine, barbiturate, cocaine, cannabis, or hallucinogen abuse by DSM-IV
criteria within 4 weeks prior to enrollment

- Medical conditions that would affect absorption, distribution, metabolism, or
excretion of study treatment

- Unstable or inadequately treated medical illness (e.g. diabetes, angina pectoris,
hypertension, congestive heart failure) as judged by the investigator

- Involvement in the planning and conduct of the study

- Previous enrollment or randomization of treatment in the present study.

- Participation in another drug trial within 4 weeks prior enrollment into this study
or longer in accordance with local requirements

- Unstable Diabetes Mellitus

- An absolute neutrophil count (ANC) of 1.5 x 109 per liter

- Past history of lack of response to an atypical antipsychotic medication or
substantial previous side effects will be cause for exclusion.

- Any medical illness that would interfere with conduct of the study will be cause for
exclusion.

- Pregnant or lactating women and women of childbearing potential not using medically
accepted means of contraception.