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: 9561563
• 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 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9561563
• 关键词: Adherence; Adverse reactions; Auditory; Auditory Evoked Potentials; Biological; Blood Platelets; Blood specimen; Brain; Chronic; 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; Woman; Work; adverse outcome; auditory stimulus; base; clinical application; cost; depressed patient; depressive symptoms; disability payment; endophenotype; follow up assessment; functional disability; health administration; 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：与创伤后应激障碍(PTSD)相关的成本是巨大的； 创伤后应激障碍影响工作效率、人际关系功能和身体健康，估计每年的成本将 退伍军人事务部的伤残抚恤金为42.8亿美元。无效的治疗在很大程度上导致了 退伍军人和广大公众的慢性创伤后应激障碍症状和功能障碍 与创伤后应激障碍相关的健康负担。选择性5-羟色胺再摄取抑制剂(SSRI)是最常见的 创伤后应激障碍患者的处方药类别。然而，许多患者对SSRIs没有反应。 没有快速、简单的方法来确定谁将或不会从这个家庭中受益 药物。 使用听觉事件相关电位(ERPs)进行用药前评估提供了一种可能的手段 预测对SSRIs的治疗反应。更具体地说，听觉诱发的响度依赖 来自对一系列日益响亮的音调的反应的电位(LDAEP)似乎是强烈的 受大脑5-羟色胺水平的影响，因此很有希望成为大脑中 对SSRIs的潜在反应性。拟议项目的主要目的是调查 LDAEP用于预测对SSRIs最有可能表现出有利或不利反应的个体。一个 次要目的是确定LDAEP的临界值，使临床医生能够个体化 基于患者的LDAEP评分的SSRI治疗决策。第三个目标是评估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之间的关系 LDAEP和SSRI对男性和女性的反应不同，以及男性和女性是否有不同的最佳反应 LDAEP截断了分数。 研究设计：94名患有创伤后应激障碍的退伍军人(男性和女性各占50%)将参加为期12周的 舍曲林试验在为期4周的单盲安慰剂引入阶段之前进行。在这项研究中嵌入了四个 评估阶段：服用安慰剂前、服用舍曲林前、服用舍曲林后1个月和3个月。这个 在每一次评估期间进行的程序将基本相同。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 包括创伤后应激障碍和抑郁症状严重程度的测量，c)对当前 用药情况、用药依从性和副作用，以及d)提供血液样本用于测量 5-羟色胺再摄取的SSRI水平和血小板测定。 临床意义：这项研究的发现可能有助于精密医学的发展 选择对患有创伤后应激障碍的退伍军人进行初步心理药理学干预的方法。发展 一种生物筛查方法，可以用来识别最有可能是 对SSRI的临床反应和那些更有可能从不同干预中受益的人可能 省去了药物提供者和患者数周的等待，看患者是否会有反应 到SSRI。它还可能有助于避免对SSRIs的不良反应。建议的方法是非侵入性的。 测试可以在大约40分钟内完成。实施所需的成本、专业知识和时间 在日常护理中，这项测试可以与心电图(EKG)相媲美。