Effectiveness of a Synergistic, Neuroplasticity-Based intervention for Rapid and Durable Suicide Risk Reduction

基于神经可塑性的协同干预措施对快速、持久降低自杀风险的有效性

• 批准号: 10471401
• 负责人: Rebecca Price
• 金额: $ 63.68万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10471401
• 关键词: Acute; Address; Adoption; Affective; Age; Antidepressive Agents; Appointment; Area; Behavior; Blinded; Brain; Cessation of life; Clinical; Cognition; Cognitive; Communities; Computers; Consult; Consultations; Data; Depressed mood; Diagnostic; Educational Intervention; Effectiveness; Enrollment; Feeling suicidal; Fostering; Future; Hospitals; Hour; Impairment; Individual; Infusion procedures; Inpatients; Intervention; Intravenous; Ketamine; Lead; Learning; Life; Literature; Measures; Medical; Medical Records; Mental Depression; Mental Health Services; Molecular Profiling; Moods; Neurocognitive; Neuronal Plasticity; Online Systems; Outcome; Outpatients; Participant; Patients; Pattern; Pharmacology; Physicians; Property; Protocols documentation; Psychiatric Hospitals; Psychiatric therapeutic procedure; Randomized; Recovery; Reporting; Research; Research Personnel; Risk; Risk Factors; Risk Reduction; Safety; Sampling; Services; Suicide; Suicide attempt; Symptoms; Techniques; Testing; Training; Training Technics; Trauma; Treatment outcome; Variant; Work; adaptive learning; arm; base; clinical effect; cognitive training; comparison group; cost; depressed patient; design; effectiveness trial; experience; feasibility testing; flexibility; follow-up; high risk; indexing; innovation; inpatient psychiatric treatment; inpatient service; interest; novel; portability; programs; prospective; reducing suicide; remote assessment; safety and feasibility; standard care; standard of care; suicidal; suicidal risk; therapy design; uptake; virtual; web app

Project Summary. Intravenous ketamine, which displays rapid antidepressant and anti-suicidality properties, is posited to reverse symptoms by rapidly enhancing neuroplasticity; but surprisingly little is known regarding its feasibility, safety, and effectiveness for reducing suicidal outcomes among real-world, heterogenous samples at imminent risk. Furthermore, a significant barrier to clinical adoption is the lack of evidence for durability of ketamine's effects, raising concerns about illusory recovery and subsequent rebound of suicide risk. We posit that ketamine will rapidly decrease suicidal ideation and rapidly increase cognitive flexibility in a real-world sample, allowing for rigid, negative biases in cognition to be rapidly reversed. We further expect these neurocognitive changes will provide a clinical window of opportunity in which to introduce 1) standard crisis-oriented psychiatric care; and 2) automated cognitive training (CT) techniques, which will consolidate adaptive forms of cognitive processing (specifically, positive and life-oriented implicit representations of self) while neuroplasticity remains high. Instantiating adaptive forms of processing (through standard care and/or automated CT) after first 'priming' the brain with ketamine represents a potentially synergistic treatment approach that could extend the acute effects of a single ketamine infusion beyond its typical 3-7 day window, efficiently fostering protective anti- suicidal effects that are both rapid and enduring. In this study, 200 Medical Unit inpatients (age 18-65) will be enrolled by referral from the psychiatric consultation/liaison service in a large Level 1 trauma hospital, following consult for a medically serious suicide attempt (SA). Leveraging medical unit physicians who are well-accustomed to utilizing ketamine infusion routinely in their inpatient medical settings, inpatients will be randomized in a parallel arm design to receive a single infusion of ketamine “pre-treatment”—shortly prior to subsequent psychiatric inpatient stay—or no- infusion. Patients will complete acute measures of explicit SI and cognitive target engagement (implicit suicide-self associations; Aim 1). In a fully crossed (2 x 2 factorial), parallel arm design, patients will then be randomized to receive a brief web-app-based cognitive training protocol during the post-infusion "window of opportunity," designed to implicitly reverse negative self-representations, instilling beneficial self-representations in their place, or a sham variant of the same training. Patients, investigators, and outcome raters will be blinded to treatment condition. Comprehensive feasibility/safety data will be captured for both intervention components. Remote assessments and the medical record will then be used to capture SI and SAs over a 12-month naturalistic follow-up to assess whether: ketamine followed by standard psychiatric inpatient care has a beneficial impact over no-infusion standard-of-care (Aim 2) and active cognitive training enhances and/or extends the durability of ketamine's effects, potentially providing an exceedingly efficient, low- cost, portable, non-invasive, safe, and highly dissemination-ready strategy (Aim 3). This study will provide novel feasibility, safety, and effectiveness data on ketamine's impact among heterogeneous real-world patients at imminent risk of suicide, and will represent a first attempt to synergistically combine ketamine with both standard and novel (cognitive training) interventions in a real-world, generalizable setting, in an effort to exploit and extend ketamine's rapid effects.

项目摘要。静脉注射氯胺酮具有快速抗抑郁和抗自杀特性，被认为可以 通过快速增强神经可塑性来逆转症状；但令人惊讶的是，人们对它的可行性、安全性知之甚少， 以及减少现实世界中处于迫在眉睫风险的异质样本中自杀结果的有效性。此外， 临床采用的一个重大障碍是缺乏氯胺酮作用持久性的证据，引起了人们的担忧 虚幻的康复和随后自杀风险的反弹。我们认为氯胺酮会迅速减少自杀意念 并迅速提高现实世界样本中的认知灵活性，从而消除认知中僵化的负面偏见 迅速逆转。我们进一步期望这些神经认知变化将提供一个临床机会窗口，其中 介绍 1) 标准的危机导向精神科护理； 2）自动认知训练（CT）技术，这将 巩固认知处理的适应性形式（特别是积极的、以生活为导向的自我内隐表征） 而神经可塑性仍然很高。实例化自适应处理形式（通过标准护理和/或自动化 CT）首先用氯胺酮“启动”大脑后代表了一种潜在的协同治疗方法，可以延长 单次氯胺酮输注的急性作用超出了其典型的 3-7 天窗口，有效地促进了保护性抗- 自杀效应既迅速又持久。在这项研究中，200 名医疗单位住院患者（年龄 18-65 岁）将被纳入 大型一级创伤医院的精神科咨询/联络服务处转诊，咨询后 医学上严重的自杀未遂（SA）。利用习惯于使用的医疗单位医生 在住院医疗环境中常规注射氯胺酮，住院患者将被随机分组​​，采用平行组设计 接受单次氯胺酮“预治疗”输注——在随后的精神科住院之前不久——或不接受 输液。患者将完成外显 SI 和认知目标参与（内隐自杀自我 协会；目标1）。在完全交叉（2 x 2 阶乘）平行臂设计中，患者将被随机分配接受 输液后“机会之窗”期间基于网络应用程序的简短认知训练方案，旨在隐式地 扭转消极的自我表征，灌输有益的自我表征取而代之，或者是相同的虚假变体 训练。患者、研究者和结果评估者将对治疗条件不知情。综合的 将为两个干预组成部分捕获可行性/安全性数据。远程评估和医疗记录将 然后用于在 12 个月的自然随访中捕获 SI 和 SA，以评估是否：氯胺酮，然后 标准精神科住院护理比无输液标准护理（目标 2）和主动认知疗法具有有益影响 训练增强和/或延长氯胺酮作用的持久性，可能提供极其有效、低- 成本、便携、非侵入性、安全和高度传播就绪的策略（目标 3）。这项研究将提供新颖的 关于氯胺酮对现实世界面临迫在眉睫风险的异质患者影响的可行性、安全性和有效性数据 自杀，并将代表将氯胺酮与标准和新颖（认知）协同结合的首次尝试 培训）在现实世界中的普遍环境中进行干预，以努力利用和扩大氯胺酮的快速效果。