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

基本信息

批准号：
10684238
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
项目类别：
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/10684238
关键词：
Acute Address Adoption Affective Age Anesthetics Antidepressive Agents Appointment Area Behavior Binding Blinded Brain Cessation of life Clinical Cognition Cognitive Communities Computers Consult Consultations Data Diagnostic Effectiveness Enrollment Feeling suicidal Fostering Future Hospitalization Hospitals Hour Impairment Individual Infusion procedures Inpatients Intervention Intravenous Ketamine Learning Life Literature Measures Medical Medical Records Mental Depression Mental Health Services Molecular Profiling Moods Neurocognitive Neuronal Plasticity Outcome Outpatients Participant Patient Preferences Patient Selection Patients Pattern Pharmacologic Actions 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 antidepressant effect arm clinical effect cognitive training comparison group cost depressed patient design effectiveness trial experience feasibility testing flexibility follow-up high risk improved indexing innovation inpatient psychiatric treatment inpatient service interest novel pharmacologic portability programs prospective reduce symptoms reducing suicide remote assessment safety and feasibility standard care standard of care suicidal suicidal risk therapy design uptake virtual web app

项目摘要

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。静脉注射氯胺酮显示出快速抗抑郁和抗杀菌性的特性，已定位为通过快速增强神经可塑性来反向症状；但是关于它的可行性，安全性，以及降低现实世界中自杀结果的有效性，即迫在眉睫的异质样本。此外，临床采用的一个重大障碍是缺乏证据表明氯胺酮效果的耐用性，从而引起了人们对虚幻的恢复和随后自杀风险的反弹。我们肯定氯胺酮将迅速降低自杀式想法并迅速提高现实世界样本中的认知灵活性，从而使认知的严格偏见是迅速逆转。我们进一步期望这些神经认知的变化将为临床机会窗口提供介绍1）标准面向危机的精神病护理； 2）自动认知培训（CT）技术，这将巩固认知处理的适应性形式（特别是积极的，面向生活的自我表示）而神经可塑性仍然很高。实例化适应性的处理形式（通过标准护理和/或自动化 ct）首先用氯胺酮“启动”大脑后，代表一种潜在的协同治疗方法，可以扩展单个氯胺酮输注的急性影响超出了其典型的3-7天窗口，有效地促进自杀效应既快速又持久。在这项研究中，将招募200名医疗单位住院患者（18-65岁）在咨询A后，来自大型1级创伤医院的精神咨询/联络服务的转诊医学上认真的自杀企图（SA）。利用良好努力使用的医疗部门医师氯胺酮在其住院医疗环境中通常会输注，住院患者将在平行手臂设计中随机分配给在随后的精神病患者住院期之前，会收到单一的注入氯胺酮的“预处理”，或者没有 - 输液。患者将完成明确的SI和认知目标参与度的急性测量（隐式自杀自杀）协会；目标1）。在完全交叉的（2 x 2阶乘）中，平行手臂设计，然后将患者随机分配以接受在关注后“机会之窗”期间，简短的基于Web应用的认知培训方案，旨在隐式地逆转负面自我代表，将有益的自我代表灌输给他们的有益的自我代表或相同的假变体训练。患者，研究人员和结果评估者将对治疗状况视而不见。综合的两种干预组件都将捕获可行性/安全性数据。远程评估和病历将然后用于在12个月的自然主义随访中捕获SI和SAS，以评估是否：氯胺酮后跟标准的精神病患者护理对无灌注标准（AIM 2）和主动认知具有有益的影响训练可以增强和/或扩展氯胺酮作用的耐用性，可能提供极其有效，低 - 成本，便携，无创，安全且高度传播的策略（AIM 3）。这项研究将提供新颖对氯胺酮在异质现实世界中对氯胺酮影响的可行性，安全性和有效性数据迫在眉睫的风险自杀，这将是首次尝试协同将氯胺酮与标准和新颖（认知）结合起来的尝试培训）在现实世界中可概括的环境中进行干预，以利用和扩展氯胺酮的快速影响。