CLINICAL TRIAL: ADJUNCTIVE RISPERIDONE IN CLOZAPINE TREATED PATIENTS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 氯氮平仍然是FDA批准用于治疗难治性精神分裂症的唯一抗精神病药物。不幸的是，对氯氮平的部分反应是常见的。在大多数对照试验中，40%到70%的耐药患者对氯氮平治疗没有足够的反应，而且没有经过证实的可行的治疗替代方案。新出现的临床实践是通过在氯氮平的基础上添加第二种抗精神病药物来治疗氯氮平无效者。在马里兰州，接受氯氮平治疗的所有患者中有15%接受第二代新一代抗精神病药物治疗，另外5%-10%接受辅助传统抗精神病药物治疗。有许多小病例系列报告，但到目前为止，几乎没有经验证据支持这种做法的有效性或安全性。在氯氮平治疗的精神分裂症患者中，利培酮和安慰剂利培酮进行为期16周的随机双盲对照研究，将达到以下主要和次要的目标：主要研究目标1.确定利培酮对氯氮平治疗的精神分裂症患者持续阳性症状的治疗是否优于安慰剂。2.确定辅助性利培酮治疗氯氮平治疗的精神分裂症患者认知功能障碍是否优于安慰剂。第二研究目的1.确定利培酮辅助治疗精神分裂症患者氯氮平持续阴性症状的疗效是否优于安慰剂。2.确定在服用氯氮平的精神分裂症患者中，与安慰剂相比，辅助利培酮是否与副作用的发生率增加有关。3.确定在氯氮平治疗的精神分裂症患者中，在治疗焦虑/抑郁和敌对症状、临床总体改善、生活质量和患者满意度方面，利培酮是否优于安慰剂。这项拟议的研究是一项随机、双盲的利培酮或安慰剂与氯氮平的比较。样本将包括90名临床稳定的住院和门诊DSM-IV精神分裂症或分裂情感障碍患者。将有为期4周的评估阶段和为期16周的治疗阶段。在为期4周的评估阶段，患者将接受基线症状、医疗、安全性、氯氮平和催乳素水平以及神经认知评估。在为期16周的治疗阶段，患者将接受两周一次的症状、副作用和生命体征评估。在研究结束时(16周)，将获得利培酮、氯氮平和催乳素水平，并将重复神经认知评估。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Clozapine remains the only antipsychotic that has been FDA approved for treatment-resistant schizophrenia. Unfortunately, partial response to clozapine is common. In most controlled trials, forty to seventy per cent of treatment-resistant patients fail to adequately respond to clozapine treatment, and there are no proven viable treatment alternatives. The emerging clinical practice is to treat clozapine non-responders by adding a second antipsychotic to clozapine. In the State of Maryland, 15% of all clozapine-treated patients are treated with a second new generation antipsychotic and an additional 5-10% treated with an adjunctive conventional antipsychotic. There are a number of small case series reports but, to date, there is little empirical evidence to support the efficacy or safety of this practice. The proposed 16-week randomized double-blind comparison of adjunctive risperidone and placebo-risperidone in clozapine-treated patients with schizophrenia will address the following primary and secondary specific aims: Primary Study Objectives 1. To determine if adjunctive risperidone is superior to placebo for the treatment of persistent positive symptoms in clozapine-treated patients with schizophrenia. 2. To determine if adjunctive risperidone is superior to placebo for the treatment of cognitive impairments in clozapine-treated patients with schizophrenia. Secondary Study Objectives 1. To determine if adjunctive risperidone is superior to placebo for the treatment of persistent negative symptoms in clozapine-treated patients with schizophrenia. 2. To determine if adjunctive risperidone is associated with increased incidence of side effects as compared to placebo in clozapine-treated patients with schizophrenia. 3. To determine if adjunctive risperidone is superior to placebo for the treatment of anxiety/depression and hostility symptoms, clinical global improvement, quality of life, and patient satisfaction with treatment in clozapine-treated patients with schizophrenia. The proposed study is a randomized, double-blind comparison of adjunctive risperidone or placebo to clozapine. The sample will consist of 90 clinically stable inpatients and outpatients with DSM-IV schizophrenia or schizoaffective disorder. There will be a 4-week evaluation phase and a 16-week treatment phase. In the 4-week evaluation phase, patients will undergo baseline symptom, medical, safety, clozapine and prolactin levels, and neurocognitive assessments. In the 16-week treatment phase, patients will receive biweekly symptom, side effect, and vital sign assessments. At the end of the study (16 weeks), ripseridone, clozapine and prolactin levels will be obtained and neurocognitive assessments will be repeated.