4/7 Clozapine for the Prevention of Violence in Schizophrenia: a Randomized Clinical Trial

4/7 氯氮平预防精神分裂症暴力：一项随机临床试验

• 批准号: 10192468
• 负责人: DEANNA L KELLY
• 金额: $ 19.31万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 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/10192468
• 关键词: Address; Aggressive behavior; Alcohol consumption; Alcohols; Antipsychotic Agents; Behavior; Clinical; Clinical Research; Clinical Trials; Clozapine; Collaborations; Communities; Data; Delusions; Development; Effectiveness; Ensure; Fostering; Future; Hostility; Human Resources; Impulsivity; Individual; Institutes; Intervention; Interview; Link; Magnetic Resonance Imaging; Measures; Multi-Institutional Clinical Trial; Murder; Neurobiology; New York; Outcome; Outcome Measure; Outpatients; Pathway interactions; Patients; Pharmaceutical Preparations; Populations at Risk; Positron-Emission Tomography; Property; Protocols documentation; Psychoses; Psychotic Disorders; Public Health; Randomized; Randomized Clinical Trials; Reporting; Research; Research Domain Criteria; Resources; Risk; Risk Reduction; Running; Safety; Sample Size; Schizophrenia; Self-Injurious Behavior; Site; Symptoms; Syndrome; Testing; Time; Violence; Vulnerable Populations; Work; antisocial behavior; blind; clinical research site; clinically relevant; community setting; effectiveness outcome; effectiveness study; efficacy trial; high risk; improved; individual patient; interest; open label; prevent; primary outcome; psychopathic personality; 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 MRI 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，大多数暴力行为都是由非精神病患者犯下的， 患有精神障碍的人暴力的风险增加，暴力与更严重的 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， 重要的公共卫生影响。一些临床研究表明，氯氮平是上级比其他 抗精神病药物在减少暴力或侵略。然而， 这些研究包括大多数是观察性和非随机的，包括小样本量， 或专注于敌意、非身体攻击或自我伤害，而不是暴力行为。此外，大多数 这些试验不能推广到门诊病人和社区。没有大型有效性研究 研究了氯氮平对社区暴力行为的影响。我们提出了一个随机的， 一项平行组、24周、开放标签、单（评估者）盲、7中心临床试验，以检查治疗效果 氯氮平与常规治疗（TAU）对280名精神分裂症患者暴力行为风险的影响， 暴力的高风险。这项试验将由7个研究中心合作进行，由纽约州精神病学中心协调。 院另外6个合作地点提供了独特的专门知识，将确保有足够的样本 这场审判的规模。我们的主要效果是时间暴力行为作为衡量麦克阿瑟 社区暴力访谈。我们还将探讨氯氮平对穴位减影的影响 攻击范式。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、冲动和物质使用，证据表明， 许多这些不同的因果影响的共同途径可能贯穿于被捕获的行为， 阳性和阴性综合征量表的兴奋因子（即，一个兴奋的分数的合成， 不合作、冲动控制差和敌意）。重要的是，我们的目标（兴奋因素的 PANSS）已被验证用于测量精神分裂症临床试验中的兴奋样症状， 在MRI和PET研究中与暴力的神经生物学有关， 氯氮平与其他抗精神病药物的区别我们还将探讨氯氮平与TAU对阳性对照的影响。 症状（例如，迫害妄想）和酒精和物质使用，以及这些影响如何影响 暴力行为的风险。为了加强本研究在这一面临风险的弱势人群中的安全实施， 暴力行为，我们将实施临床安全和治疗参与协议， 人员，这将是很容易推广。本试验将提供使用氯氮平的指导， 社区环境中的暴力，并将明确测试有关其反暴力机制的假设 方面的影响.结果将立即与实践相关，并将影响公共卫生，因为 目前没有治疗精神分裂症暴力的标准方法。