7/7 Clozapine for the Prevention of Violence in Schizophrenia: a Randomized Clinical Trial

7/7 氯氮平预防精神分裂症暴力：一项随机临床试验

• 批准号: 10655396
• 负责人: Joseph Patrick McEvoy
• 金额: $ 19.25万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10655396
• 关键词: Address; Aggressive behavior; Alcohol consumption; Alcohols; Antipsychotic Agents; Behavior; Clinical; Clinical Research; Clinical Trials; Clozapine; Collaborations; Communities; Data; Delusions; Development; Diagnostic; Disparate; Effectiveness; Ensure; Fostering; Future; Hostility; Human Resources; Impulsivity; Individual; Intervention; Interview; Link; Measures; Multi-Institutional Clinical Trial; Murder; Neurobiology; New York; Outcome; Outcome Measure; Outpatients; Pathway interactions; Patients; Persons; Pharmaceutical Preparations; Populations at Risk; Positron-Emission Tomography; Property; Protocols documentation; Psychoses; Psychotic Disorders; Public Health; Randomized; Research; Research Domain Criteria; Resources; Risk; Risk Reduction; Running; Safety; Sample Size; Schizophrenia; Sedation procedure; Self-Injurious Behavior; Site; Spectrum Analysis; Symptoms; Syndrome; Testing; Time; Violence; Vulnerable Populations; Work; antisocial behavior; blind; clinical research site; clinically relevant; community setting; community violence; effectiveness outcome; effectiveness study; efficacy trial; high risk; improved; individual patient; interest; intervention delivery; open label; prevent; primary outcome; psychopathic personality; psychotic; randomized, clinical trials; service delivery; social stigma; substance use; treatment as usual; treatment effect; violence prevention

Project Summary While most people with psychosis are not dangerous and most violence is committed by non-psychotic people, people with psychotic disorders are at increased risk for violence, and violence is associated with worse outcomes and increased stigma. Therefore, decreasing violence risk in psychosis is clinically relevant and has important public health implications. Several clinical studies suggest that clozapine is superior to other antipsychotic medications in reducing violence or aggression. However, there were numerous limitations of these studies including that most of them were observational and non-randomized, included small sample sizes, or focused on hostility, non-physical aggression, or self-harm, rather than violent acts. Further, the majority of these trials were not generalizable to outpatient, community settings. No large effectiveness study has examined the effects of clozapine on violent behavior in community settings. We propose a randomized, parallel-group, 24-week, open-label, single (rater)-blind, 7-site clinical trial to examine the effects of treatment with clozapine vs. treatment as usual (TAU) on the risk of violent acts in 280 individuals with schizophrenia at high risk for violence. This trial will be a collaboration of 7 sites, coordinated by the New York State Psychiatric Institute. The 6 additional collaborating sites contribute unique expertise and will ensure an adequate sample size for this trial. Our primary effectiveness outcome is time to violent acts as measured by the MacArthur Community Violence Interview (MCVI). We will also explore the effects of clozapine on the Point Subtraction Aggression Paradigm. While many factors may contribute to violent behavior in individuals with schizophrenia, including positive symptoms, psychopathy, impulsivity, and substance use, evidence suggests that the final common pathway for many of these disparate causal influences likely runs through behaviors captured by the Excitement Factor of the Positive and Negative Syndrome Scale (i.e., a composite of the scores of excitement, uncooperativeness, poor impulse control, and hostility). Importantly, our target (the excitement factor of the PANSS) has been validated to measure excitement-like symptoms in clinical trials in schizophrenia, is sensitive to treatment, has been linked to the neurobiology of violence in spectroscopy and PET studies, and differentiates clozapine from other antipsychotic drugs. We will also explore the effects of clozapine vs. TAU on positive symptoms (e.g., persecutory delusions) and alcohol and substance use, and how these effects influence the risk for violent acts. To enhance the safe implementation of this study in this vulnerable population at risk of violent behaviors, we will implement clinical safety and treatment engagement protocols that rely upon standard personnel and that will be readily generalizable. This trial will provide guidance on the use of clozapine for violence in community settings and will definitively test hypotheses regarding mechanisms of its anti-violence effects. The results will be immediately relevant to practice and will impact public health because there is currently no standard approach for the treatment of violence in schizophrenia.

项目摘要 虽然大多数精神病患者并不危险，而且大多数暴力行为都是由非精神病患者实施的， 患有精神障碍的人遭受暴力的风险更高，而暴力与更糟糕的情况有关 结果和增加的耻辱。因此，降低精神病患者的暴力风险具有临床意义 对公共卫生的重要影响。多项临床研究表明，氯氮平优于其他 抗精神病药物在减少暴力或攻击方面的作用。然而，有许多限制， 这些研究包括大多数是观察性的和非随机的，包括小样本， 或者专注于敌意、非身体攻击或自我伤害，而不是暴力行为。此外，大多数人 这些试验不能推广到门诊、社区环境中。没有大规模的有效性研究 研究了氯氮平对社区环境中暴力行为的影响。我们提出了一种随机的、 平行分组，24周，开放标签，单(评价者)盲，7点临床试验，以检查治疗的效果 氯氮平与常规治疗(TAU)对280例精神分裂症患者暴力行为风险的比较 发生暴力的风险很高。这项试验将由7个地点合作，由纽约州精神病学协会协调 研究所。另外6个协作站点提供了独特的专业知识，并将确保提供足够的样本 这次试验的大小。我们的主要有效结果是按照麦克阿瑟的标准来衡量暴力行为的时间 社区暴力访谈(MCVI)。我们还将探讨氯氮平对积分减法的影响 攻击性范式。虽然许多因素可能导致精神分裂症患者的暴力行为， 包括阳性症状、精神病、冲动和药物使用，证据表明最终的 许多这些不同的因果影响的共同途径可能贯穿于 积极和消极症状量表的兴奋因素(即兴奋分数的合成， 不合作、控制不好的冲动和敌意)。重要的是，我们的目标(刺激因素 PANSS)在临床试验中已被证实可用于测量精神分裂症的兴奋样症状，是敏感的 在光谱学和正电子发射计算机断层扫描研究中，与暴力的神经生物学有关，以及 将氯氮平与其他抗精神病药物区分开来。我们还将探讨氯氮平与TAU对患者的影响。 阳性症状(如受迫害妄想症)、酗酒和吸毒，以及这些影响 影响暴力行为的风险。加强这项研究在这一弱势群体中的安全实施 在存在暴力行为的风险下，我们将实施临床安全和治疗参与协议，这些协议依赖于 标准人员，这将很容易推广。这项试验将为氯氮平的使用提供指导 针对社区环境中的暴力，并将最终测试关于其反暴力机制的假设 效果。结果将立即与实践相关，并将影响公共健康，因为 目前还没有治疗精神分裂症暴力的标准方法。