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: 10291767
• 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 2023-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10291767
• 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).

背景和目的：创伤后应激障碍（PTSD）的相关费用是巨大的; 创伤后应激障碍影响工作效率，关系功能和身体健康，估计每年的费用， 残疾人补贴42.8亿美元。无效的治疗在很大程度上助长了 退伍军人的慢性创伤后应激障碍症状和功能障碍，因此， 与PTSD相关的健康负担。选择性5-羟色胺再摄取抑制剂（SSRI）是最常见的 为PTSD患者开的处方药。然而，许多患者对SSRIs没有反应， 没有一种快速、简单的方法来确定谁会或不会从这个家庭中受益， 药物治疗 使用听觉事件相关电位（ERP）进行的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），来自对一系列越来越响亮的音调的反应，似乎是强烈的 受大脑5-羟色胺水平的影响，因此有相当大的希望作为大脑功能的指标 对SSRIs的潜在反应。拟议项目的主要目的是调查 LDAEP用于预测那些最有可能对SSRIs产生有利或不利反应的个体。一 第二个目的是确定LDAEP截止值，使临床医生能够做出个性化的诊断。 根据患者的LDAEP评分决定SSRI治疗。第三个目的是评估LDAEP作为一种 SSRI反应的客观结果测量。一个探索性的目标将测试是否之间的关系， LDAEP和SSRI反应对男性和女性不同，男性和女性是否有不同的最佳 LDAEP截断分数。 研究设计：94名患有PTSD的退伍军人（50%男性; 50%女性）将参加为期12周的 舍曲林试验之前是为期4周的单盲安慰剂导入期。在这项研究中，有四个 评估阶段：安慰剂治疗前、舍曲林治疗前、舍曲林治疗后1个月和3个月。的 每次评估会议的程序大致相同。与会者将：（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）完成当前的自我报告评估 药物使用、药物依从性和副作用，以及d）提供血液样品用于测量 SSRI水平和5-羟色胺再摄取的血小板测量。 临床意义：这项研究的结果可能有助于精确医学的发展 在为患有PTSD的退伍军人选择最初的心理药理学干预时，发展 一种生物筛选方法，可以用来识别那些最有可能被 临床上对SSRI有反应的人和那些更有可能从不同的干预措施中受益的人， 节省了药物提供者和患者数周的等待时间， 一个SSRI它还可以帮助避免对SSRIs的不良反应。所提出的方法是非侵入性的 并且测试可以在约40分钟内进行。实施所需的费用、专门知识和时间 在常规护理中，该测试可以想象与心电图（EKG）的测试相当。