Antipsychotics and the Risk of Unexpected Death in Children and Youth

抗精神病药物与儿童和青少年意外死亡的风险

基本信息

批准号：
10084784
负责人：
WAYNE A RAY
金额：
$ 63.24万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-01-01 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10084784
关键词：
Address Adolescent Adult Adverse effects Age-Years Aggressive behavior Antipsychotic Agents Anxiety Anxiety Disorders Attention deficit hyperactivity disorder Behavior Disorders Benefits and Risks Bipolar Disorder Cardiovascular system Case Study Central Nervous System Depressants Cessation of life Child Chlorpromazine Clinical Data Databases Death Certificates Depressive disorder Disease Dose Evaluation Growth Incidence Incidence Study Individual Injury Life Link Medicaid Metabolic Minor Mood Disorders Neurologic Effect Overdose Patients Persons Pharmaceutical Preparations Population Predisposition Prevalence Psychoses Public Health Risk Role Safety Schizophrenia Structure Suicide Surrogate Endpoint Tennessee Testing Therapeutic Therapeutic Intervention Therapeutic Uses alternative treatment atypical antipsychotic base cardiovascular risk factor clinical practice comorbidity mortality mortality risk respiratory risk minimization

项目摘要

Each year an estimated 1.3 million persons ≤24 years of age receive 7 million antipsychotic prescriptions in the U.S. Although the primary indications for antipsychotics are schizophrenia and related psychoses, with no other treatment alternatives, an estimated 90% of antipsychotic prescriptions for children and youth are for other, less serious conditions, including attention-deficit/hyperactivity disorder (ADHD), disruptive or aggressive behaviors, affective disorders including bipolar disorder, and anxiety. However, other recommended therapeutic interventions for children and youth with these disorders are thought to have fewer adverse effects. Antipsychotics, which increase the risk of cardiovascular and all-cause mortality in adults, have serious adverse cardiovascular, metabolic, respiratory, and neurologic effects in children and adolescents that plausibly increase the risk of death in this population. We recently found that antipsychotic users of doses>50mg chlorpromazine equivalents (median starting dose) had a greater than 3-fold increased risk of unexpected death, leading to a 64% increase in total mortality (HR = 1.64 [1.03-2.63]). In contrast, the adjusted risk of deaths from injuries or suicides did not increase nor was there increased risk of death from any cause for lower doses of antipsychotics. Our data indicate antipsychotics increase risk of unexpected deaths, particularly cardiovascular deaths. The increased risk is clinically meaningful: the incidence of unexpected death in higher-dose antipsychotic users equaled that of injuries and suicides, which account for two-thirds of deaths in children and adolescents. Thus, death should be considered as a potential harm when prescribing antipsychotics for children and youth. However, to guide clinical practice, data are needed that define antipsychotic-related mortality: 1) according to antipsychotic indication; and 2) according to important factors that practitioners can control: a) individual drug, b) dose, and c) concurrent central nervous system (CNS) depressants. We will address these questions using the national Medicaid Analytical Extract (MAX) database, which includes more than 15 years of longitudinal data that can be linked to death certificates for the estimated 39% of children in the U.S. who are Medicaid enrollees. There are two specific aims: Aim 1: Test the hypothesis that the risk of unexpected deaths and total mortality in children and youth who are antipsychotic new users with a) ADHD or disorders of behavior/conduct, b) unipolar depressive or anxiety disorders, or c) bipolar disorders is greater than that for comparable patients starting alternative medications. Aim 2: Define how risk of unexpected deaths and total mortality in children and youth who are antipsychotic new users varies with a) individual drug, b) dose, and c) concurrent CNS depressants.

每年估计有 130 万名 ≤24 岁的人接受 700 万粒抗精神病药物尽管抗精神病药物的主要适应症是精神分裂症及相关疾病，但在美国仍存在处方精神病，在没有其他治疗选择的情况下，估计 90% 的抗精神病药处方儿童和青少年适用于其他不太严重的疾病，包括注意力缺陷/多动症（多动症）、破坏性或攻击性行为、情感障碍（包括双相情感障碍）和焦虑。然而，针对患有这些疾病的儿童和青少年的其他推荐治疗干预措施是认为不良反应较少。抗精神病药会增加成人心血管疾病和全因死亡的风险，具有严重的副作用对儿童和青少年的不良心血管、代谢、呼吸和神经系统影响我们最近发现抗精神病药物使用者可能会增加这一人群的死亡风险。剂量>50mg氯丙嗪当量（中位起始剂量）的风险增加3倍以上意外死亡，导致总死亡率增加 64%（HR = 1.64 [1.03-2.63]）。调整后的受伤或自杀死亡风险并未增加，因受伤或自杀而死亡的风险也没有增加任何原因导致抗精神病药剂量降低。我们的数据表明，抗精神病药物会增加意外死亡的风险，特别是心血管死亡。增加的风险具有临床意义：高剂量抗精神病药物中意外死亡的发生率用户的死亡人数相当于受伤和自杀，这占儿童和儿童死亡人数的三分之二。因此，在为青少年开抗精神病药物时，应将死亡视为潜在危害。然而，为了指导临床实践，需要定义抗精神病药物相关的数据。死亡率：1) 根据抗精神病药物适应症；2) 根据医生认为的重要因素可以控制：a) 个体药物，b) 剂量，以及 c) 并发中枢神经系统 (CNS) 抑制剂。我们将使用国家医疗补助分析提取 (MAX) 数据库来解决这些问题，该数据库包括超过 15 年的纵向数据，这些数据可以与死亡证明相关联，以估计估计的死亡人数。 39% 的美国儿童参加了医疗补助计划有两个具体目标：目标 1：检验以下假设：儿童和青少年意外死亡和总死亡率的风险是抗精神病药物新使用者，患有 a) ADHD 或行为/行为障碍，b) 单相抑郁症或焦虑症，或 c) 双相情感障碍大于开始替代治疗的可比患者药物。目标 2：确定服用抗精神病药物的儿童和青少年的意外死亡风险和总死亡率新使用者因 a) 个体药物、b) 剂量和 c) 并发中枢神经系统抑制剂而异。