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

Conditions

Borderline Personality Disorder

Keywords

Borderline Personality Disorder, BPD, Seroquel, Seroquel XR, quetiapine, quetiapine extended-release

Brief summary

The Primary objective of this study is to evaluate Seroquel XR in the treatment of borderline personality disorder (BPD). As in many initial randomized control trials, the study will be of relatively short duration - 8 weeks - to assess effectiveness and safety while maximizing retention. The specific aim is to determine if Seroquel XR is superior to placebo. The primary outcome measure will be a statistically significant difference between Seroquel XR compared to placebo on the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD), an objective rating scale that addresses the severity of Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) symptoms of the illness. As there is the recent development of an extended release form of Seroquel (Seroquel XR) (Schulz et al. 2007), the new compound may offer several advantages in this study. Therefore, the hypothesis of this study is that both doses of Seroquel XR (see below) will be superior to placebo in an 8-week randomized trial as assessed by the ZAN-BPD. To achieve the Primary Objective of this study, two doses of Seroquel XR will be tested - 150 mg/d and 300 mg/d. Thus, the study will be able to assess the effect of Seroquel XR compared to placebo and to explore a dose effect.

Detailed description

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 Body Mass Index (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.

Related papers

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Interventions

DRUGquetiapine extended-release

Seroquel XR 150mg/day vs Seroquel XR 300mg/day vs Placebo

DRUGPlacebo

Seroquel XR 150mg/day vs Seroquel XR 300mg/day vs Placebo

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 45 Years

Healthy volunteers

No

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.

Design outcomes

Primary

Measure	Time frame	Description
Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD)	baseline, weekly until week 8	This is an assessment of change in DSM-IV borderline psychopathology. Consisting of nine criteria rated on a five-point anchored rating scale of 0 to 4, yielding a total score of 0 to 36. 0 being the best and 4 meaning the worse.
Montgomery-Åsberg Depression Rating Scale (MADRS)	baseline to 8 weeks	Nine criteria rated on a six-point anchored rating scale of 0 to 6, yielding a total score of 0 to 60. O is the least and 6 is the highest 0 to 6 - normal /symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression \>34 - severe depression.
Borderline Evaluation of Severity Over Time (BEST)	Baseline to 8 weeks	Scale including 15 items and three subscales. All items are rated on a Likert-like scale. A correction factor of 15 is added to yield the final score which can range from 12 (best) to 72 (worst).
Overt Aggression Scale - Modified (OAS-M)	Change from Baseline Overt Aggression Scale - Modified to 8 weeks	Four part behavior rating scale designed to measure four types of aggressive behavior as witnessed in the past week. Each section consists of five questions. Total scores on the MOAS range from 0-40. 0 is the best and 40 is the worst of symptoms Reduction in scores shows a change of symptoms.
Global Assessment of Functioning Scale (GAF)	Change in Global Assessment of Functioning from Baseline to 8 weeks	Numeric scale (1 through 100) used by mental health clinicians and physicians to rate subjectively the social, occupational, and psychological functioning of adults. 100 is the highest level of functioning. O is the least functional
Barratt Impulsiveness Scale (BIS)	Change in Impulsiveness from Baseline to 8 weeks	30-item self-report questionnaire, that is scored to yield a total score, three second-order factors, and six first-order factors. patients rate the questions 1-4 1 being the least and 4 being the most.
Symptom Checklist -90-Revised (SCL-90-R)	Change in psychological problems and symptoms from Baseline to 8 weeks	90 items measured on a Likert scale via self-report. Scale is 0-5 stating 0= strongly disagree and 5 is Strongly agree Measures psychological problems and symptoms
Young Mania Rating Scale (YMS)	Change in manic symptoms from Baseline to 8 weeks	Eleven-item multiple choice diagnostic questionnaire, yielding total scores of 0-60. 0-4 rating 0-being least likely and 4 being most likely This scale assess manic symptoms
Sheehan Disability Scale (SDS)	Change in functional impairment from Baseline to 8 weeks	Three self-rated items, on a scale of 0-10. 0 is unimpaired 10 is highly impaired This measures functional impairment

Countries

United States

Participant flow

Recruitment details

This randomized, double-blind, placebo-controlled, dose comparison trial was conducted at three outpatient treatment centers from January 2010 to March 2013.

Pre-assignment details

Ninety-five persons with Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) borderline personality disorder (BPD) were randomly assigned to quetiapine XR 150 mg/day (n=33), quetiapine XR 300 mg/day (n=33), or placebo (n=29).

Participants by arm

Arm	Count
Quetiapine XR 150 mg/Day (n=33), Seroquel XR 150mg oral tablets taken daily for 8 weeks.	33
Quetiapine XR 300 mg/Day (n=33), Seroquel XR 300mg oral tablets taken daily for 8 weeks.	33
Placebo (n=29). Equivalent number of placebo oral tablets taken daily for 8 weeks.	29
Total	95

Baseline characteristics

Characteristic	Quetiapine XR 300 mg/Day (n=33),	Placebo (n=29).	Quetiapine XR 150 mg/Day (n=33),	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	33 Participants	29 Participants	33 Participants	95 Participants
Age, Continuous	30.2 years STANDARD_DEVIATION 8.1	20.1 years STANDARD_DEVIATION 8.8	28.2 years STANDARD_DEVIATION 8	29.5 years STANDARD_DEVIATION 8.3
Region of Enrollment United States	33 participants	29 participants	33 participants	95 participants
Sex: Female, Male Female	23 Participants	19 Participants	25 Participants	67 Participants
Sex: Female, Male Male	10 Participants	10 Participants	8 Participants	28 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	29 / 33	30 / 33	19 / 29
serious Total, serious adverse events	0 / 33	0 / 33	0 / 29

Outcome results

Primary

Barratt Impulsiveness Scale (BIS)

30-item self-report questionnaire, that is scored to yield a total score, three second-order factors, and six first-order factors. patients rate the questions 1-4 1 being the least and 4 being the most.

Time frame: Change in Impulsiveness from Baseline to 8 weeks