A Randomized, Double-blind, Placebo-controlled Study of Quetiapine SR and Divalproex Sodium ER on Anxiety in Bipolar Disorder With at Least Moderately Severe Current Anxiety and Lifetime Panic or Generalized Anxiety Disorder.
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 224
- 试验地点
- 3
- 主要终点
- Change From Baseline in the CGI-21 Anxiety
研究概览
简要总结
The specific aim of this study is to evaluate the efficacy, tolerability, and safety of quetiapine SR monotherapy and divalproex sodium ER monotherapy in comparison to placebo in the treatment of ambulatory bipolar disorder with co-morbid lifetime panic disorder or generalized anxiety disorder and current at least moderately severe anxiety.
详细描述
This is a randomized, double-blind, placebo controlled, parallel-group, 8-week trial of quetiapine SR monotherapy compared to divalproex sodium ER monotherapy in outpatient subjects with a lifetime bipolar I, II, or not otherwsise specified (NOS) disorder, a lifetime panic or generalized anxiety disorder, and current diagnosis at least moderately severe anxiety symptoms. Approximately 180 subjects will be randomized to obtain 90 subjects who complete the 8-week trial (30 completers per treatment group). This calculation is based on drop out rates in a similar patient population carried out by this group of collaborators. Subjects will be randomized to quetiapine SR or divalproex sodium ER or placebo in a 1:1:1 ratio. No concomitant psychotropic medication will be allowed throughout the study except for prn lorazepam during the first two weeks for the management of affective and anxiety symptoms, prn zolpidem and zaleplon for the management of insomnia and benztropine for the management of extrapyramidal side effects (EPS). Throughout the study, psychiatric scales will be used to assess psychiatric symptoms and the presence of treatment-emergent adverse events will be monitored and recorded.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subjects must be at least 18 years of age and not older than 65
- •Subjects must have lifetime bipolar I, II, or not otherwise specified (NOS) disorder as defined by DSM-IV TR (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision) criteria
- •Subjects must have lifetime panic disorder or generalized anxiety disorder (GAD) as defined by DSM-IV, criteria (except clause "does not occur exclusively during a mood disorder" of Criterion F for GAD)
- •Subjects' bipolar symptoms must be no more than moderate in severity, defined as a CGI-BP< 4
- •Subjects' anxiety symptoms must be at least moderate in severity, defined as a CGI-S > 4
- •Subjects must not be receiving regular mood stabilizing, antidepressant, antipsychotic, or anxiolytic medication for at least one week prior to baseline. Patients receiving fluoxetine or depot antipsychotics should be off these medications for at least four weeks prior to baseline
- •Subjects or their legally authorized representative must sign the Informed Consent Document after the nature of the trial has been fully explained
- •If female, subjects must be: postmenopausal, surgically incapable of childbearing, or practicing medically acceptable effective method(s) of contraception (e.g., hormonal methods, barrier methods, intrauterine device) for at least one month prior to study entry and throughout the study
排除标准
- •Subjects who do not have lifetime bipolar disorder by DSM-IV-TR criteria
- •Subjects who do not have lifetime panic disorder or generalized anxiety disorder by DSM-IV-TR criteria
- •Subjects who are receiving treatment with an anti-manic or mood stabilizing medication (lithium, valproate, carbamazepine, or an antipsychotic), and in the investigators' judgment, require ongoing treatment with that medication
- •Subjects whose bipolar symptoms are presently more than moderately severe (CGI-BP>5)
- •Subjects whose anxiety symptoms are presently less than moderately severe (CGI-S<3)
- •Subjects with clinically significant suicidal or homicidal ideation.
- •Subjects with a current DSM-IV TR Axis I diagnosis of delirium, dementia, amnesia, or other cognitive disorders; a DSM-IV TR diagnosis of a substance dependence disorder within the past six months; a lifetime DSM-IV TR psychotic disorder (e.g., schizophrenia or schizoaffective disorder)
- •Subjects with serious general medical illnesses including hepatic, renal, respiratory, cardiovascular, endocrine, neurological, or hematological disease as determined by the clinical judgment of the clinical investigator. Subjects with hypo-or hyperthyroidism unless stabilized on thyroid replacement > 3 months
- •Subjects with a clinically significant abnormality in their pre-study physical exam, vital signs, EKG, or laboratory tests
- •Subjects who are allergic to or who have demonstrated hypersensitivity or intolerance to either of the active study medications
- •Women who are pregnant or nursing
- •Subjects who have received an experimental drug or used an experimental device within 30 days
- •Subjects who have a history of neuroleptic malignant syndrome
- •A patient with diabetes mellitus (DM) fulfilling one of the following criteria:
- •Unstable DM defined as enrollment glycosylated hemoglobin (HbAlc) >8.5%
- •Admitted to hospital for treatment of DM or DM related illness within the past 12 weeks
- •Not under physician care for DM
- •Physician responsible for patient's DM care has not indicated that the patient's DM is controlled
- •Physician responsible for patient's DM care has not approved the patient's participation in the study
- •Has not been on the same dose of oral hypoglycemic drug(s) and/or diet for the 4 weeks before randomization. For thiazolidinediones (glitazones) this period should not be less than 8 weeks before randomization
- •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 Note: If a patient with DM meets one of these criteria, the patient is to be excluded even if the treating physician believes that the patient is stable and can participate in the study
研究组 & 干预措施
Quetiapine SR
Quetiapine SR (Quetiapine Sustained Release)
干预措施: quetiapine SR (Drug)
Divalproex Sodium ER
Divalproex Sodium ER (Divalproex Sodium Extended Release)
干预措施: divalproex sodium ER (Drug)
Placebo
placebo
干预措施: placebo (Drug)
结局指标
主要结局
Change From Baseline in the CGI-21 Anxiety
时间窗: 8 weeks (using LOCF Repeated Measures ANOVA)
The CGI-21 Anxiety is a 21-point clinician-rated global improvement for anxiety symptoms. Response range: -10 to +10. The higher the score the more improvement. At Baseline all patients have a score of "0" (zero), against which any subsequent improvements or deterioration is assessed. The relative efficacy of the 3 treatments was tested with a last-observation-carried forward (LOCF) repeated-measures analysis of variance (ANOVA). The focus was on the "treatment-by-time" effect showing whether the trajectory of response differed over time by treatment group. Also, group differences in baseline-to-endpoint changes in the efficacy measure were tested using LOCF ANOVA followed by pairwise planned comparisons (t-tests). The least square means shown here are from the LOCF baseline-to-endpoint ANOVA. Outcomes showing scores above zero indicate that patients did better, i.e. showed improvement on this scale.
次要结局
- Change From Baseline on Patient Global Improvement Scale (PGI-21) for Anxiety Symptoms(8 weeks)
- Change From Baseline in Hamilton Anxiety Scale (HAM-A) Scores(8 weeks)
- Change From Baseline in Sheehan Panic Disorder Scale (SPS)(8 weeks)
- Change From Baseline on Montgomery Asberg Depression Rating Scale (MADRS)(8 weeks)
- Change From Baseline in Young Mania Rating Scale (YMRS)(8 weeks)
- Change From Baseline on Clinician Global Impression Scale for Bipolar Disorder (CGI-BP) (Overall Severity)(8 weeks)
- Change From Baseline on Rapid Ideas Scale (RISc)(8 weeks)
- Change From Baseline in Sheehan Irritability Scale (SIS)(8 weeks)
- Change From Baseline on Sheehan Disability Scale (SDS) - Total(8 weeks)
- Change From Baseline on Sheehan- Suicidality Tracking Scale S-STS (2008 Version With 8 Items)(8 weeks)