Antipsychotics and the Risk of Unexpected Death in Children and Youth

据估计，每年有130万24岁的≤人服用700万抗精神病药物 美国的处方。尽管抗精神病药物的主要适应症是精神分裂症和相关疾病 在没有其他治疗选择的情况下，估计90%的抗精神病药物处方用于 儿童和青少年患有其他不太严重的疾病，包括注意力缺陷/多动障碍 多动症(ADHD)、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，对于患有这些疾病的儿童和青少年，其他推荐的治疗干预措施有 被认为有较少的不良反应。 抗精神病药物会增加成人心血管疾病和各种原因死亡的风险，具有严重的 对儿童和青少年的心血管、代谢、呼吸系统和神经系统的不良影响 合理地增加了这一人群的死亡风险。我们最近发现抗精神病药物的使用者 剂量为50毫克的氯丙嗪当量(起始量的中位数)使患病风险增加3倍以上。 意外死亡导致总死亡率增加%(HR=1.64[1.03-2.63])。相比之下， 调整后的受伤或自杀死亡风险没有增加，也没有增加 任何导致较低剂量抗精神病药物的原因。 我们的数据表明，抗精神病药物增加了意外死亡的风险，特别是心血管死亡。 增加的风险具有临床意义：大剂量抗精神病药物意外死亡的发生率 用户与受伤和自杀人数持平，后者占儿童死亡人数的三分之二， 青少年。因此，在给患者开抗精神病药物时，应将死亡视为潜在的危害。 儿童和青年。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)根据抗精神病药物的适应症；2)根据从业者的重要因素 可以控制：a)单独用药，b)剂量，c)同时服用中枢神经系统(CNS)抑制剂。 我们将使用国家医疗补助分析摘录(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，这些数据可以与估计的 在美国参加医疗补助的儿童中，有39%。有两个具体目标： 目标1：检验以下假设：儿童和青年意外死亡和总死亡率 抗精神病药物的新使用者是否患有a)ADHD或行为/品行障碍，b)单相抑郁或 焦虑症，或c)双相情感障碍比开始替代治疗的可比患者更严重 药物。 目标2：确定服用抗精神病药物的儿童和青年意外死亡的风险和总死亡率 新使用者因a)单独用药、b)剂量和c)同时服用中枢神经系统抑制剂而异。

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.