Importance Dose-related effects of antipsychotic medications may increase mortality in children and young adults. Objective To compare mortality for patients aged 5 to 24 years beginning treatment with antipsychotic vs control psychiatric medications. Design, Setting, and Participants This was a US national retrospective cohort study of Medicaid patients with no severe somatic illness or schizophrenia or related psychoses who initiated study medication treatment. Study data were analyzed from November 2022 to September 2023. Exposures Current use of second-generation antipsychotic agents in daily doses of less than or equal to 100-mg chlorpromazine equivalents or greater than 100-mg chlorpromazine equivalents vs that for control medications (α agonists, atomoxetine, antidepressants, and mood stabilizers). Main Outcome and Measures Total mortality, classified by underlying cause of death. Rate differences (RDs) and hazard ratios (HRs) adjusted for potential confounders with propensity score-based overlap weights. Results The 2 067 507 patients (mean [SD] age, 13.1 [5.3] years; 1 060 194 male [51.3%]) beginning study medication treatment filled 21 749 825 prescriptions during follow-up with 5 415 054 for antipsychotic doses of 100 mg or less, 2 813 796 for doses greater than 100 mg, and 13 520 975 for control medications. Mortality was not associated with antipsychotic doses of 100 mg or less (RD, 3.3; 95% CI, -5.1 to 11.7 per 100 000 person-years; HR, 1.08; 95% CI, 0.89-1.32) but was associated with doses greater than 100 mg (RD, 22.4; 95% CI, 6.6-38.2; HR, 1.37; 95% CI, 1.11-1.70). For higher doses, antipsychotic treatment was significantly associated with overdose deaths (RD, 8.3; 95% CI, 0-16.6; HR, 1.57; 95% CI, 1.02-2.42) and other unintentional injury deaths (RD, 12.3; 95% CI, 2.4-22.2; HR, 1.57; 95% CI, 1.12-2.22) but was not associated with nonoverdose suicide deaths or cardiovascular/metabolic deaths. Mortality for children aged 5 to 17 years was not significantly associated with either antipsychotic dose, whereas young adults aged 18 to 24 years had increased risk for doses greater than 100 mg (RD, 127.5; 95% CI, 44.8-210.2; HR, 1.68; 95% CI, 1.23-2.29). Conclusions and Relevance In this cohort study of more than 2 million children and young adults without severe somatic disease or diagnosed psychosis, antipsychotic treatment in doses of 100 mg or less of chlorpromazine equivalents or in children aged 5 to 17 years was not associated with increased risk of death. For doses greater than 100 mg, young adults aged 18 to 24 years had significantly increased risk of death, with 127.5 additional deaths per 100 000 person-years.

中文翻译：

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儿童和年轻人的抗精神病药物和死亡率。

重要性 抗精神病药物的剂量相关作用可能会增加儿童和年轻人的死亡率。目的 比较 5 至 24 岁开始接受抗精神病药物与对照精神科药物治疗的患者的死亡率。设计、设置和参与者 这是一项美国国家回顾性队列研究，研究对象为没有严重躯体疾病或精神分裂症或相关精神病且开始研究药物治疗的医疗补助患者。对 2022 年 11 月至 2023 年 9 月的研究数据进行了分析。 暴露 目前使用的第二代抗精神病药每日剂量小于或等于 100 mg 氯丙嗪当量或大于 100 mg 氯丙嗪当量与对照药物（α 激动剂）的比较、阿托莫西汀、抗抑郁药和情绪稳定剂）。主要成果和措施 总死亡率，按根本死因分类。使用基于倾向得分的重叠权重针对潜在混杂因素进行了率差 (RD) 和风险比 (HR) 调整。结果 2 067 507 名患者（平均 [SD] 年龄，13.1 [5.3] 岁；1 060 194 名男性 [51.3%]）开始研究药物治疗，在随访期间开出了 21 749 825 份处方，其中 5 415 054 份抗精神病药物剂量为 100 mg 或以下，剂量大于 100 mg 为 2 813 796，对照药物为 13 520 975。死亡率与 100 mg 或更少的抗精神病药物剂量无关（RD，3.3；95% CI，-5.1 至 11.7 每 10 万人年；HR，1.08；95% CI，0.89-1.32），但与剂量更大相关低于 100 mg（RD，22.4；95% CI，6.6-38.2；HR，1.37；95% CI，1.11-1.70）。对于较高剂量，抗精神病药物治疗与过量死亡（RD，8.3；95% CI，0-16.6；HR，1.57；95% CI，1.02-2.42）和其他意外伤害死亡（RD，12.3；95% CI，0-16.6）显着相关，2.4-22.2；HR，1.57；95% CI，1.12-2.22），但与非过量自杀死亡或心血管/代谢死亡无关。5 至 17 岁儿童的死亡率与任一抗精神病药物剂量均无显着相关性，而 18 至 24 岁的年轻人服用剂量超过 100 mg 的风险增加（RD，127.5；95% CI，44.8-210.2；HR，1.68） ；95% CI，1.23-2.29）。结论和相关性 在这项对超过 200 万没有严重躯体疾病或诊断出精神病的儿童和年轻人进行的队列研究中，剂量为 100 毫克或更少的氯丙嗪当量或 5 至 17 岁儿童的抗精神病治疗与风险增加无关死亡。如果剂量大于 100 毫克，18 至 24 岁的年轻人的死亡风险显着增加，每 10 万人年增加 127.5 人死亡。