The Efficacy and Tolerability of Seroquel XR Combined With a Selective Serotonin Re-Uptake Inhibitor Versus Seroquel XR Monotherapy in the Acute Treatment of Major Depressive Disorder With Psychotic Features
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Depression
研究概览
简要总结
The purpose of this study is to compare the efficacy and tolerability of Seroquel monotherapy for the treatment of Major Depression with Psychotic features with Seroquel plus Selective Serotonin Reuptake Inhibitor.
详细描述
The proposed study is designed to investigate the non-inferiority of treatment of PsyD using monotherapy with quetiapine XR versus combination treatment using quetiapine XR and an SSRI (sertraline or citalopram or escitalopram) during the acute phase of treatment. The primary outcome measures will be the change rates of symptoms of depression (as measured on the Hamilton Rating Scale for Depression [HAM-D-17] and psychosis (as measured on the Brief Psychiatric Rating Scale [BPRS] Positive Symptoms Subscale).
The secondary aim of the study is to assess the safety and efficacy of the combination of quetiapine XR and SSRIs in patients with the diagnosis of PsyD. Metabolic factors including fasting glucose, fasting insulin, and fasting lipids (total cholesterol, HDL, LDL, and triglycerides) will be obtained at screen and at the 8-week endpoint of the study to assess the impact of treatment on the development of risk factors for metabolic syndrome. Measures of cognitive function (MGH Cognitive and Physical Functioning Questionnaire and RBANS) (Fava et al. 2006; Randolph et al. 1998) will be obtained at screen and the 8-week endpoint of the study to assess the impact of treatment on cognitive function.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent
- •Diagnosis of Major Depressive Disorder with Psychotic Features by the DSM-IV
- •Females and Males between the ages of 18-85 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 enrolment
- •Able to understand and comply with the requirements of the study
- •Initial HAM-D-17 score of > 16, both at the screen visit and at the baseline visit.
- •Participants must have an initial BPRS score of > 25 and at least one of the following: > 5 for item 1, > 5 for item 5, > 5 for item 8, > 4 for item 9, > 1 for item 10, > 1 for item 11; these BPRS criteria msut be met both at the screen visit and at the baseline visit.
- •Participants must have an initial CGI score of > 2, both at the screen visit and at the baseline visit.
排除标准
- •Pregnancy or lactation
- •Any DSM-IV Axis I disorder not defined in the inclusion criteria
- •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 enrolment 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 within the past three months (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 enrolment
- •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) as judged by the investigator
- •Involvement in the planning and conduct of the study
- •Previous enrolment 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
- •A patient with Diabetes Mellitus (DM) fulfilling one of the following criteria:
- •Unstable DM defined as enrollment glycosylated hemoglobin (HbA1c) > 8.5%.
- •Admitted to hospital for treatment of DM or DM related illness in past 12 weeks.
- •Not under physician care for DM.
- •Physician responsible for patient's DM care has not indicated that patient's DM is controlled.
- •Physician responsible for patient's DM care has not approved patient's participation in the study
- •Has not been on the same dose of oral hypoglycaemic drug(s) and/or diet for the 4 weeks prior to randomization. For thiazolidinediones (glitazones) this period should not be less than 8 Weeks.
- •Taking insulin whose daily dose on one occasion in the past 4 weeks has been more than 10% above or below their mean dose in the preceding 4 weeks
- •An absolute neutrophil count (ANC) of 1.5 x 10^9 per liter
- •Patients with a history seizure disorder; unstable physical disorders (cardiovascular, hepatic, renal, respiratory, endocrine, neurologic, or hematologic); or any physical disorder judged to significantly affect central nervous system function.
- •Patients who are currently treated with antidepressants other than the selective serotonin reuptake inhibitors, with mood stabilizing or antipsychotic drugs other than quetiapine.
- •Patients with known arrhythmias or arrhythmias noted on screening EKG.
- •Outpatients with a CGI score of 7.
研究组 & 干预措施
Quetiapine
Patients assigned to receive Quetiapine
干预措施: Quetiapine (Drug)
Quetiapine and SSRI
Patients assigned to receive Quetiapine and SSRI
干预措施: Quetiapine (Drug)
Quetiapine and SSRI
Patients assigned to receive Quetiapine and SSRI
干预措施: escitalopram (Drug)
Quetiapine and SSRI
Patients assigned to receive Quetiapine and SSRI
干预措施: Sertraline (Drug)
Quetiapine and SSRI
Patients assigned to receive Quetiapine and SSRI
干预措施: Citalopram (Drug)
结局指标
主要结局
Depression
时间窗: 8 weeks
Depression measured with Hamilton Rating Scale for Depression 17 (HAM-D) at baseline and 8 weeks. Ham D 17 scores range from 0-52, 52 being the most severe.
Psychosis
时间窗: 8 weeks
Psychosis measured by Brief Psychosis Rating Scale (BPRS) at baseline and 8 weeks. Scores range from 24-168, with 168 bring the most severe.
次要结局
- RBANS (Repeatable Battery for Assessment of Neuropsychological Status) Total Score(8)
- CPFQ (Cognitive and Psychological Functioning Questionnaire)(8 weeks)
- Fasting Blood Glucose(8 weeks)
- RBANS (Repeatable Battery for Assessment of Neuropsychological Status) Visuospatial/Constructional Sub-scale.(8 weeks)
- RBANS (Repeatable Battery for Assessment of Neuropsychological Status) Immediate Memory Sub-scale Score(8 weeks)
- RBANS (Repeatable Battery for Assessment of Neuropsychological Status) Language Sub-scale Score.(8 weeks)
- RBANS (Repeatable Battery for Assessment of Neuropsychological Status) Delayed Memory Subscale Scores at Baseline and Week 8.(8 weeks)
- Blood Level of Total Cholesterol Levels Were Collected at Baseline and Week 8.(8 weeks)
- Blood Level of Triglycerides at Baseline and Week 8.(8 weeks)
- LDL Blood Levels at Baseline and Week 8.(8 weeks)
- Blood Hemoglobin A1C at Baseline and Week 8.(8 weeks)
- RBANS (Repeatable Battery for Assessment of Neuropsychological Status) Attention Sub-scale Scores at Baseline and Week 8.(8 weeks)
- HDL Blood Levels at Baseline and Week 8.(8 weeks)
研究者
John D. Matthews
Director of Inpatient Research & Training
Massachusetts General Hospital