SSRI-Induced Activation Syndrome In Pediatric OCD

SSRI 诱导的儿童强迫症激活综合征

• 批准号: 7162453
• 负责人: Wayne K Goodman
• 金额: $ 29.67万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-18 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7162453
• 关键词: adolescence (12-20); anxiety; attention deficit disorder; behavior test; behavioral /social science research tag; clinical depression; clinical research; clinical trials; diagnosis design /evaluation; dosage; drug adverse effect; human subject; impulsive behavior; longitudinal human study; mental disorder diagnosis; middle childhood (6-11); obsessive compulsive disorder; pathologic process; pediatrics; serotonin inhibitor; sertraline; suicide; syndrome

DESCRIPTION (provided by applicant): Intro: An FDA re-analysis of pediatric clinical trials (N about 4400) in psychiatric conditions found that the risk of suicidal ideation and behavior (suicidality) was significantly higher with antidepressants (4%) compared to placebo (2%). These data revealed that the suicidality signal was not limited to depression: subjects with OCD and other anxiety disorders also exhibited this higher risk. Although the mechanism responsible for this effect is unknown, induction of an "activation syndrome" (e.g., irritability, restlessness, emotional lability, etc.) may represent an intermediary state change that promotes suicidality. SSRI-induced activation syndrome is well-accepted by clinicians and thought to be common, particularly in children and teens. However, there is a dearth of empirical data on the phenomenology and quantification of this putative syndrome. We conceptualize activation syndrome as behavioral toxicity (an adverse event) that occurs relatively independent of the underlying diagnosis, while acknowledging that various factors may modify susceptibility and expression (e.g., age, dosing, pharmacogenetics, comorbidity, etc.). Better characterization of activation syndrome and its timing might point to the mechanisms mediating this adverse effect as well as approaches to its mitigation. Specific Aims are: 1. To formalize and quantify a cluster of behavioral side effects of SSRIs, referred to as "activation syndrome" and 2. To confirm the occurrence and timing of activation syndrome during SSRI treatment. Approach: The first phase will entail an iterative process of arriving at consensus on the content domains corresponding to activation syndrome, selection and revision of measures, creation of a composite measure and testing of reliability in a representative sample of children and adolescents at various stages of treatment with SSRIs. In the second phase, children and adolescents with OCD will be randomized in double-blind fashion to either 1) sertraline at standard dosing (RegSert); 2) sertraline slow titration (SloSert); or 3) pill placebo (Pla) for 18 weeks. All groups will receive CBT for their OC symptoms starting after week 4. We predict that measures of activation syndrome will be elevated early (first days or 2 weeks) during RegSert compared to PLA. We will explore if SloSert reduces frequency or intensity of activation syndrome compared to RegSert. Conducting this study in OCD offers pragmatic advantages (e.g., clarity of diagnosis), yet findings should be generalizable to other diagnostic groups. Significance: SSRIs induce an activation syndrome (consisting of irritability, agitation, mood swings, etc.) that may be a precursor to suicidality in some individuals. Improved recognition and understanding of activation syndrome should prompt interventions (e.g., slower dosing of antidepressants) that might reduce the risk of developing suicidality. Development of an activation syndrome measurement tool will be useful in future large-scale clinical trials that test the relationship between activation syndrome and suicidality.

描述（由申请人提供）：简介： FDA 对精神疾病儿科临床试验（N 约 4400 项）的重新分析发现，与安慰剂相比，抗抑郁药 (4%) 的自杀意念和行为（自杀）风险显着更高(2%)。这些数据表明，自杀信号不仅限于抑郁症：患有强迫症和其他焦虑症的受试者也表现出较高的风险。尽管造成这种效应的机制尚不清楚，但“激活综合征”（例如烦躁、不安、情绪不稳定等）的诱发可能代表促进自杀的中间状态变化。 SSRI 诱发的激活综合征已被临床医生广泛接受，并被认为很常见，尤其是在儿童和青少年中。然而，缺乏关于这种假定综合症的现象学和量化的经验数据。我们将激活综合征概念化为行为毒性（不良事件），其发生相对独立于潜在诊断，同时承认各种因素可能改变易感性和表达（例如年龄、剂量、药物遗传学、合并症等）。更好地表征激活综合征及其发生时间可能会指出介导这种不利影响的机制以及缓解其的方法。具体目标是： 1. 正式确定和量化 SSRI 的一系列行为副作用（称为“激活综合征”）； 2. 确认 SSRI 治疗期间激活综合征的发生和时间。方法：第一阶段将需要一个迭代过程，就与激活综合症相对应的内容领域达成共识，选择和修订措施，创建综合措施，并在不同阶段的儿童和青少年代表性样本中测试可靠性。使用 SSRIs 治疗。在第二阶段，患有强迫症的儿童和青少年将以双盲方式随机接受：1）标准剂量的舍曲林（RegSert）； 2)舍曲林慢速滴定(SloSert)；或 3) 服用安慰剂 (Pla) 18 周。所有组将在第 4 周后开始针对 OC 症状接受 CBT。我们预测与 PLA 相比，RegSert 期间激活综合征的测量值将提前（第一天或两周）升高。我们将探讨与 RegSert 相比，SloSert 是否会降低激活综合征的频率或强度。在强迫症中进行这项研究具有务实的优势（例如诊断的清晰度），但研究结果应该可以推广到其他诊断组。意义：SSRIs 会诱发激活综合征（包括烦躁、激动、情绪波动等），这可能是某些个体自杀的先兆。提高对激活综合征的认识和理解应该促使采取干预措施（例如减慢抗抑郁药的剂量），这可能会降低自杀风险。激活综合征测量工具的开发将有助于未来测试激活综合征与自杀之间关系的大规模临床试验。