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

• 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
• 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

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130万人≤24岁的人会接受700万个抗精神病药 尽管抗精神病药的主要迹象是精神分裂症和相关的 精神病没有其他治疗替代方案，估计有90％的抗精神病药处方 儿童和青少年适合其他严重的条件，包括注意力缺陷/多动症障碍 （多动症），破坏性或侵略性行为，包括躁郁症和动画在内的情感障碍。 但是，针对这些疾病的儿童和青少年的其他建议的治疗干预措施是 被认为具有较少的不利影响。 抗精神病药会增加成人心血管和全因死亡率的风险 儿童和青少年的不良心血管，代谢，呼吸和神经系统作用 可能会增加该人群死亡的风险。我们最近发现 剂量> 50mg氯丙嗪当量（中位开始剂量）的风险增加了3倍以上 意外死亡，导致总死亡率增加64％（HR = 1.64 [1.03-2.63]）。相反， 受伤或自杀死亡的调整风险没有增加，也没有增加死亡风险 较低剂量抗精神病药的任何原因。 我们的数据表明，抗精神病药会增加意外死亡的风险，尤其是心血管死亡。 风险增加在临床上有意义：高剂量抗精神病药物中意外死亡的事件 用户等于受伤和自杀，这是儿童死亡的三分之二的 青少年。那就是在开处方抗精神病药时，应将死亡视为潜在的伤害 儿童和青年。但是，为指导临床实践，需要数据定义抗精神病药 死亡率：1）根据抗精神病药的指示； 2）根据从业者的重要因素 可以控制：a）单个药物，b）剂量和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物（MAX）数据库解决这些问题，该数据库 包括超过15年的纵向数据，可以链接到估计的死亡证书 美国有39％的儿童参加了医疗补助。有两个具体的目标： 目的1：检验以下假设：儿童和青少年发生意外死亡和全死死亡的风险 是具有A）ADHD或行为/行为障碍的抗精神病药新用户，b）单极抑郁症或 焦虑症，或c）双相情感障碍大于可比患者的焦虑症 药物。 目标2：定义抗精神病药的儿童和青少年意外死亡和总死亡率的风险如何 新用户随a）单独药物，b）剂量和c）同时发生的CNS抑制剂而变化。