SSRIs and Self-harm in Borderline Personality Disorder

SSRIs 与边缘性人格障碍中的自残

• 批准号: 8134231
• 负责人: EMIL Frank COCCARO
• 金额: $ 53.28万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-25 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8134231
• 关键词: Acute; Affective; Age; Aggressive behavior; Auditory Evoked Potentials; Behavior; Borderline Personality Disorder; Boxing; Case Study; Clinical Trials; Data; Dependence; Depressed mood; Depressive disorder; Diagnosis; Disease; Double-Blind Method; Emotions; Escitalopram; Exposure to; Feeling suicidal; Functional disorder; Genetic; Genetic Polymorphism; Home environment; Impulsivity; Individual; Institutes; Label; Laboratories; Lead; Link; Loudness; Major Depressive Disorder; Measurement; Measures; Medical; Mental Depression; Meta-Analysis; Methodology; Methods; Outcome; Participant; Patient Self-Report; Patients; Pharmaceutical Preparations; Pharmacological Treatment; Phase; Placebos; Population; Psychophysiology; Randomized; Randomized Clinical Trials; Reporting; Research; Risk; Sampling; Selective Serotonin Reuptake Inhibitor; Self-Injurious Behavior; Serotonin; Suicide; Suicide prevention; Symptoms; Thinking; Time; analog; base; blind; clinically relevant; economic cost; ideation; indexing; information processing; promoter; prospective; public health relevance; randomized trial; reducing suicide; response; social; suicidal; suicide rate; trait; translational approach; trial comparing; week trial

DESCRIPTION: Suicide and lesser forms of intentional self-harm behaviors produce devastating medical, social and economic costs. Self-harm is integrally related to depressive disorders and Borderline Personality Disorder. Selective Serotonin Reuptake Inhibitors (SSRIs), like escitalopram, are front-line pharmacological treatments for these disorders, putatively regulating depressed mood and reducing suicidality. However, data from case studies and retrospective meta-analyses of depression clinical trials is mixed, with some (but not all ) studies suggesting that during the first months of treatment, SSRIs may increase the risk of suicidal ideation in select individuals, particularly younger individuals. These post-hoc analyses, though informative, are based on studies that provide limited sampling of the self-harm domain. No study, to date, has implemented a direct prospective examination of the effects of early SSRI use on self-harm thoughts and behaviors using a multi-method measurement involving both the laboratory (standard self-aggression paradigm: SAP) and home environments (ecological momentary assessment: EMA). Also, no study has examined the influence of impaired 5-HT function and emotion dysregulation as moderators of outcome with escitalopram. The proposed randomized clinical trial will prospectively assess the impact of eight weeks exposure to SSRI treatment on self-harm ideation and behavior among a sample of 200 subjects with Borderline Personality Disorder and current major depression. After a one week single-blind placebo lead-in, participants will be randomly assigned double blind to either placebo or escitalopram for eight (8) weeks. The primary dependent variable will be EMA of self-harm ideation and behavior obtained several times each day. Self-harm will also be assessed using a laboratory analogue task (SAP) at baseline and again after the eight week trial. Age will be evaluated as a moderator of SSRI response. 5-HT dysfunction and emotion dysregulation will be evaluated as candidate moderators of SSRI response. 5-HT functioning will be assessed using psychophysiological (loudness dependence of the auditory evoked potential: LDAEP) and genetic (5-HT transporter promoter polymorphism: 5-HTTLPR) markers. Measures of emotion dysregulation will include trait aggression, impulsivity and socioemotional information processing. At the conclusion of the eight-week randomized trial, all participants will receive eight weeks of escitalopram administered single-blind, with continued EMA and other assessment. PUBLIC HEALTH RELEVANCE: The proposed randomized clinical trial will prospectively assess the impact of 8 weeks exposure to SSRI treatment on self-harm ideation and behavior among a sample of 200 subjects with Borderline Personality Disorder and current major depression. After a one week single-blind placebo lead-in, participants will be randomly assigned double blind to either placebo or escitalopram daily for eight (8) weeks. The primary dependent variable will be EMA of self-harm ideation and behavior obtained several times each day. Selfharm will also be assessed using a laboratory analogue task (SAP) at baseline and again after the eight week trial. Age, 5-HT dysfunction and emotion dysregulation will be evaluated as potential moderators of SSRI response.

描述：自杀和较轻形式的故意自残行为会产生毁灭性的医疗、社会和经济代价。自我伤害与抑郁障碍和交界性人格障碍密切相关。选择性5-羟色胺再摄取抑制剂(SSRI)，如艾司西妥兰，是治疗这些疾病的一线药物，可能调节抑郁情绪 并减少自杀率。然而，来自案例研究和回顾性荟萃分析的数据 抑郁症的临床试验是混合的，一些(但不是所有)研究表明，在第一个阶段 经过几个月的治疗，SSRIs可能会增加特定个人，特别是年轻个人自杀念头的风险。这些事后分析虽然提供了信息，但基于对自我伤害领域提供的有限样本的研究。到目前为止，还没有研究使用实验室(标准的自我攻击范式：SAP)和家庭环境(生态瞬间评估：EMA)的多方法测量来对早期使用SSRI对自我伤害思想和行为的影响进行直接的前瞻性检验。此外，还没有研究考察5-羟色胺功能受损和情绪失调作为依西他普兰治疗结果的调节因素的影响。这项拟议的随机临床试验将前瞻性地评估接受SSRI治疗8周对200名患有交界性人格障碍和当前严重抑郁症的受试者的自我伤害意念和行为的影响。在一周的单盲安慰剂导入后，参与者将被随机分配到双盲安慰剂或艾司匹林，为期八(8)周。主要的因变量将是每天多次获得的自残念头和行为的均方根均值。自我伤害也将在基线时使用实验室模拟任务(SAP)进行评估，并在八周试验后再次进行。年龄将被评估为SSRI反应的调节因素。5-羟色胺功能障碍和情绪失调将被评估为SSRI反应的候选调节因素。5-羟色胺功能将使用心理生理学(听觉诱发电位响度相关性：LDAEP)和遗传学(5-羟色胺转运体启动子多态性：5-HTTLPR)标记物进行评估。情绪失调的衡量标准将包括特质攻击性、冲动和社会情绪信息处理。在为期八周的随机试验结束时，所有参与者都将接受为期八周的单盲艾司西普兰治疗，并继续进行EMA和其他评估。 公共卫生相关性：拟议的随机临床试验将前瞻性地评估接受SSRI治疗8周对200名患有交界性人格障碍和当前严重抑郁症的受试者的自我伤害意念和行为的影响。在一周的单盲安慰剂导入后，参与者将被随机分配给每天服用安慰剂或艾司匹兰的双盲患者，为期八(8)周。主要的因变量将是每天多次获得的自残念头和行为的均方根均值。自我伤害也将在基线时使用实验室模拟任务(SAP)进行评估，并在八周试验后再次进行。年龄、5-羟色胺功能障碍和情绪失调将被评估为SSRI反应的潜在调节因素。