An Open-label Pilot Study to Examine the Value of Substituting Quetiapine for Benzodiazepines in Treatment-refractory Patients With Unipolar Depression or Generalized Anxiety Disorder and Chronic Benzodiazepine Use
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Montgomery Asberg Depression Rating Scale (MADRS)
研究概览
简要总结
The hypothesis of this study is that symptoms of anxiety, depression and insomnia; and indices of psychosocial function will all improve, while BZ use will decrease significantly during a twelve-week trial period of substituting quetiapine for benzodiazepines.
详细描述
1.1 Background Numerous patients having depression or anxiety appear to use benzodiazepines chronically and respond incompletely to conventional antidepressants. These patients are more likely to request or incur frequent changes of medication because of non-response, incomplete response or intolerance. The hypothesis of this study is that symptoms of anxiety, depression and insomnia; and indices of psychosocial function will all improve, while BZ use will decrease significantly during a twelve-week trial period of substituting quetiapine for benzodiazepines.
1.2 Rationale for this study The scientific rationale for this derives from a combination of clinical observation and a review of the literature. Anecdotal clinical experience with numerous patients having depression or anxiety suggested to me that patients with chronic benzodiazepine use were less likely to respond or remit with conventional antidepressants and more likely to request or incur frequent changes of medication because of non-response, incomplete response or intolerance. Although most of these patients were not drug abusers and the doses they took were within ranges recommended in the package inserts for these drugs (e.g., 5-20mg/ day of diazepam or equivalent), they were "dependent" in the sense that they took the BZ daily or almost daily, would not give it up in spite of "good responses" (although often with residual symptoms of anxiety or insomnia) to antidepressants or mood stabilizers, and were determined to get their prescription refills on time and often upset if they could not. I hypothesized that chronic benzodiazepine use created circadian or ultradian cycles of sedation, which might be experienced as fatigue or amotivation, and withdrawal, which might be experienced as anxiety or insomnia. Patients often tinkered with the doses and timing of the doses in an attempt to smooth out these cycles. The current study will determine whether symptoms of anxiety, depression and insomnia; and indices of psychosocial function improve, while BZ use decreases during a twelve-week trial period of substituting quetiapine for benzodiazepines. This would be a proof of concept study in a unique subpopulation with MDD or GAD.
- STUDY OBJECTIVES 2.1 Primary objective For MDD:The primary efficacy measures will be change from baseline to endpoint in the MADRAS and the change in mean daily benzodiazepine dose in diazepam equivalents during the past week.
For GAD: The primary efficacy measures will be change from baseline to endpoint in the HAM-A and the change in mean daily benzodiazepine dose in diazepam equivalents during the past week.
2.2 Secondary objectives Secondary efficacy measures will include response and remission rates and self-rated scales of symptoms and psychosocial function (the IDS-SR for depressive symptoms, the SAS-SR for social/vocational function and the Q-LES-Q for quality of life).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- 否
入选标准
- •For inclusion in the study subjects must fulfil all of the following criteria:
- •Provision of written informed consent
- •A diagnosis of a current major depressive episode (n =20) or generalized anxiety disorder (n = 20) of at least 4 weeks duration, as defined by Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition (DSM-IV) and assessed on the SCID. Subjects may be included if they meet criteria for double depression, i.e., current major depression with antecedent dysthymic disorder, major depression in partial remission or bipolar depression. MDD subjects must have a 24 item Hamilton Depression Rating Scale Score (HAM-D) at intake >/=
- •GAD subjects must have a Hamilton Anxiety Rating Scale Score (HAM-A) at intake >/=
- •Patients who meet criteria for current GAD only during a current episode of MDD will be considered to have MDD, according to DSM-IV convention.
- •Females and/or males aged 18-65 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
- •All subjects must report BZ use more days than not persistent for more than 6 months and a stable regimen of mood stabilizers and/or antidepressant medication for at least 8 weeks.
排除标准
- •Any of the following is regarded as a criterion for exclusion from the study:
- •Pregnancy or lactation
- •Any DSM-IV Axis I disorder not defined in the inclusion criteria
- •Axis II diagnosis of antisocial, schizotypal or severe borderline personality disorder(defined as patients who are high risk for being unable to complete the study due to hospitalization, suicide attempts, significant self-mutilation, or other self-injurious or destructive behavior).
- •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 randomisation
- •Substance or alcohol dependence at enrolment (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 randomisation of treatment in the present study.
- •Participation in another drug trial within 4 weeks prior enrolment into this study or longer in accordance with local requirements
研究组 & 干预措施
Quetiapine
Dosing will begin with Seroquel-XR 50 mg. at bedtime and will escalate weekly to Seroquel-XR 100mg., Seroquel-XR 200mg. and Seroquel-XR 300 mg depending on clinical response and side effects.
干预措施: quetiapine (Drug)
结局指标
主要结局
Montgomery Asberg Depression Rating Scale (MADRS)
时间窗: 12 weeks
For MDD: The primary efficacy measures will be change from baseline to endpoint in the MADRS and the change in mean daily benzodiazepine dose in diazepam equivalents during the past week. Range is 0 (least severe) to 50 (most severe).
次要结局
未报告次要终点