An electrophysiological predictor of SSRI response in Veterans with PTSD

患有 PTSD 的退伍军人中 SSRI 反应的电生理预测因子

• 批准号: 10427234
• 负责人: Suzanne Pineles
• 金额: --
• 依托单位: VA BOSTON HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10427234
• 关键词: Adherence; Adverse reactions; Auditory; Auditory Evoked Potentials; Biological; Blood Platelets; Blood specimen; Brain; Chronic Post Traumatic Stress Disorder; Clinic; Clinical; Data; Dependence; Development; Diagnosis; Electrocardiogram; Electrophysiology (science); Event-Related Potentials; Family; Female; Future; Goals; Human Resources; Impulsivity; Individual; Intervention; Lead; Loudness; Measurement; Measures; Mental Depression; Methodology; Methods; Norepinephrine; Outcome Measure; Participant; Patient Self-Report; Patients; Personality; Pharmaceutical Preparations; Phase; Placebos; Population; Post-Traumatic Stress Disorders; Prediction of Response to Therapy; Premedication; Procedures; Productivity; Provider; Public Health; Randomized Clinical Trials; Recommendation; Recording of previous events; Research; Research Design; Sampling; Selective Serotonin Reuptake Inhibitor; Series; Serotonin; Sertraline; Severities; Single-Blind Study; Site; Statistical Data Interpretation; Suicide attempt; Symptoms; Technology; Testing; Time; Training; Veterans; Veterans Health Administration; Woman; Work; adverse outcome; auditory stimulus; base; clinical application; cost; depressed patient; depressive symptoms; disability payment; endophenotype; follow up assessment; functional disability; ineffective therapies; male; medication compliance; men; neurotransmission; physical conditioning; precision medicine; predictive test; psychiatric symptom; psychopharmacologic; response; reuptake; screening; side effect; transmission process; treatment as usual; treatment response

Background and Aims: The costs associated with posttraumatic stress disorder (PTSD) are substantial; PTSD impacts work productivity, relationship functioning, and physical health, with estimated annual costs to VA in disability payments of $4.28 billion. Ineffective treatments substantially contribute to the perpetuation of chronic PTSD symptoms and functional impairment in Veterans and, as a consequence, the enormous public health burden associated with PTSD. Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed class of medications for patients with PTSD. However, many patients are not responsive to SSRIs and there is no rapid, uncomplicated way to determine who will or will not benefit from this family of medications. A pre-medication assessment using auditory event-related potentials (ERPs) offers a possible means for predicting treatment response to SSRIs. More specifically, Loudness Dependence of Auditory Evoked Potentials (LDAEP), derived from responses to a series of increasingly loud tones, appears to be strongly influenced by brain serotonin level and thereby holds considerable promise as an indicator of the brain’s potential responsiveness to SSRIs. The primary aim of the proposed project is to investigate the usefulness of LDAEP for predicting those individuals who will most likely show a favorable or adverse response to SSRIs. A secondary aim is to determine LDAEP cut-off values that would enable a clinician to make an individualized SSRI treatment decision based on a patient’s LDAEP score. A tertiary aim is to evaluate LDAEP as an objective outcome measure of SSRI response. An exploratory aim will test whether the relationships between LDAEP and SSRI response differ for men and women and whether men and women have different optimal LDAEP cut off scores. Study Design: A sample of 94 Veterans with PTSD (50% male; 50% female) will participate in a 12-week sertraline trial preceded by a 4-week single-blinded placebo lead-in phase. Embedded in this study are four assessment sessions: pre-placebo, pre-sertraline, and one and three months after initiating sertraline. The procedures conducted during each assessment session will be mostly the same. Participants will: a) engage in the ERP procedure that will yield the LDAEP score, b) complete a battery of symptom outcome measures including measures of PTSD and depressive symptom severity, c) complete self-report assessments of current medication use, medication adherence, and side effects, and d) provide a blood sample for measurement of SSRI level and platelet measurement of serotonin reuptake. Clinical Implications: Findings from this study may contribute to development of a precision-medicine approach when choosing an initial psychopharmacological intervention for Veterans with PTSD. Development of a biological screening method that can be used to identify those individuals who are most likely to be clinically responsive to an SSRI and those who are more likely to benefit from a different intervention could save the medication provider and patient weeks of waiting to see whether or not the patient will be responsive to an SSRI. It may also aid in avoiding adverse reactions to SSRIs. The proposed methodology is noninvasive and the test can be administered in about 40 minutes. The costs, expertise and time necessary to implement this test in usual care would conceivably be comparable to that of an electrocardiogram (EKG).

背景和目标：与创伤后应激障碍（PTSD）相关的成本是巨大的； 创伤后应激障碍 (PTSD) 会影响工作效率、人际关系功能和身体健康，预计每年会造成以下损失： VA 的伤残补助金为 42.8 亿美元。无效的治疗在很大程度上导致了疾病的持续存在 退伍军人以及广大公众的慢性 PTSD 症状和功能障碍 与 PTSD 相关的健康负担。选择性血清素再摄取抑制剂（SSRI）是最常见的 为 PTSD 患者开出的处方药物类别。然而，许多患者对 SSRIs 没有反应 并且没有快速、简单的方法来确定谁会或不会从这个家族中受益 药物。 使用听觉事件相关电位 (ERP) 进行用药前评估提供了一种可能的方法 预测对 SSRIs 的治疗反应。更具体地说，听觉诱发的响度依赖性 电位 (LDAEP) 源自对一系列越来越响亮的音调的响应，似乎强烈 受大脑血清素水平的影响，因此作为大脑功能的指标具有很大的前景 对 SSRIs 的潜在反应。拟议项目的主要目的是研究 LDAEP 用于预测那些最有可能对 SSRI 表现出有利或不利反应的个体。一个 第二个目标是确定 LDAEP 截止值，使临床医生能够制定个性化的治疗方案。 SSRI 治疗决策基于患者的 LDAEP 评分。第三个目标是将 LDAEP 评估为 SSRI 反应的客观结果衡量标准。探索性目标将测试之间的关系是否 男性和女性的 LDAEP 和 SSRI 反应不同，男性和女性是否有不同的最佳选择 LDAEP 削减分数。 研究设计：94 名患有 PTSD 的退伍军人（50% 男性；50% 女性）样本将参加为期 12 周的研究 舍曲林试验之前进行为期 4 周的单盲安慰剂导入阶段。这项研究中包含四个 评估阶段：安慰剂前、舍曲林前以及开始服用舍曲林后一到三个月。这 每次评估会议期间进行的程序基本相同。参与者将： a) 参与 将产生 LDAEP 评分的 ERP 程序，b) 完成一系列症状结果测量 包括 PTSD 和抑郁症状严重程度的测量，c) 对当前情况的完整自我报告评估 药物使用、药物依从性和副作用，以及 d) 提供血样用于测量 血清素再摄取的 SSRI 水平和血小板测量。 临床意义：这项研究的结果可能有助于精准医学的发展 为患有 PTSD 的退伍军人选择初始心理药理学干预时的方法。发展 一种生物筛选方法，可用于识别那些最有可能被感染的个体 对 SSRI 具有临床反应并且更有可能从不同干预措施中受益的人可以 为药物提供者和患者节省数周的等待时间，看看患者是否会做出反应 至 SSRI。它还可能有助于避免 SSRI 的不良反应。所提出的方法是非侵入性的 大约40分钟即可完成测试。实施所需的成本、专业知识和时间 可以想象，这种常规护理测试可与心电图 (EKG) 相媲美。