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）：介绍：在精神病疾病中对儿科临床试验的FDA重新分析（n左右）发现，与抗抑郁药（4％）相比，自杀念头和行为的风险（自杀性）明显更高（2％）。这些数据表明，自杀信号不仅限于抑郁：强迫症和其他焦虑症的受试者也表现出更高的风险。尽管导致这种效果的机制尚不清楚，但诱导“激活综合征”（例如，烦躁不安，不安，情绪不稳定等）可能代表促进自杀性的中间状态变化。 SSRI诱导的激活综合征受到临床医生的良好接受，尤其是在儿童和青少年中。然而，关于该推定综合征的现象学和量化的经验数据很少。我们将激活综合征概念化为行为毒性（一种不良事件），这种毒性相对独立于潜在的诊断，同时承认各种因素可能会改变易感性和表达（例如，年龄，给药，药物遗传学，合并症等）。更好地表征激活综合征及其时机可能指出了介导这种不利影响以及缓解方法的机制。具体目的是：1。为SSRI的行为副作用形式化和量化，称为“激活综合征”和2。确认SSRI治疗期间激活综合征的发生和时机。方法：第一阶段将需要一个迭代的过程，即在与激活综合征，测量的选择和修订相对应的内容域达成共识，创建复合度量的选择以及在各个治疗阶段的儿童和青少年的代表性样本中的可靠性。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分配至1）标准剂量下的舍曲林（regsert）； 2）舍法林慢滴定（slosert）；或3）丸安慰剂（PLA）18周。所有组将从第4周后开始接受CBT的OC症状。我们预测，与PLA相比，在Regsert期间，激活综合征的测量将提高（第一天或2周）。我们将探索Slosert是否与Regsert相比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实用的优势（例如，诊断的清晰度），但发现应该推广到其他诊断组。意义：SSRI诱导激活综合征（包括易怒，躁动，情绪波动等），这可能是某些人自杀的先驱。改善对激活综合征的认识和理解应促使干预措施（例如，抗抑郁药的给药较慢）可能会降低产生自杀性的风险。激活综合征测量工具的开发将在未来测试激活综合征与自杀性之间关系的大规模临床试验中有用。