Department of Health Policy, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Department of Psychiatry and Behavioral Science, Division of Child and Adolescent Psychiatry, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
J Child Adolesc Psychopharmacol. 2024 Nov;34(9):397-406. doi: 10.1089/cap.2024.0047. Epub 2024 Sep 13.
The incidence of neuroleptic malignant syndrome (NMS), a rare, potentially fatal adverse effect of antipsychotics, among children and youth is unknown. This cohort study estimated NMS incidence in antipsychotic users age 5-24 years and described its variation according to patient and antipsychotic characteristics. We used national Medicaid data (2004-2013) to identify patients beginning antipsychotic treatment and calculated the incidence of NMS during antipsychotic current use. Adjusted hazard ratios (HRs) assessed the independent contribution of patient and antipsychotic characteristics to NMS risk. The 1,032,084 patients had 131 NMS cases during 1,472,558 person-years of antipsychotic current use, or 8.9 per 100,000 person-years. The following five factors independently predicted increased incidence: age 18-24 years (HR [95% CI] = 2.45 [1.65-3.63]), schizophrenia spectrum and other psychotic disorders (HR = 5.86 [3.16-10.88]), neurodevelopmental disorders (HR = 7.11 [4.02-12.56]), antipsychotic dose >200mg chlorpromazine-equivalents (HR = 1.71 [1.15-2.54]), and first-generation antipsychotics (HR = 4.32 [2.74-6.82]). NMS incidence per 100,000 person-years increased from 1.8 (1.1-3.0) for those with none of these factors to 198.1 (132.8-295.6) for those with 4 or 5 factors. Findings were essentially unchanged in sensitivity analyses that restricted the study data to second-generation antipsychotics, children age 5-17 years, and the 5 most recent calendar years. In children and youth treated with antipsychotics, five factors independently identified patients with increased NMS incidence: age 18-24 years, schizophrenia spectrum and other psychotic disorders, neurodevelopmental disorders, first-generation drugs, and antipsychotic doses greater than 200 mg chlorpromazine-equivalents. Patients with 4 or 5 of these factors had more than 100 times the incidence of those with none. These findings could improve early identification of children and youth with elevated NMS risk, potentially leading to earlier detection and improved outcomes.
神经阻滞剂恶性综合征（NMS）是一种罕见的、潜在致命的抗精神病药物不良反应，在儿童和青少年中的发病率尚不清楚。本队列研究估计了 5-24 岁年龄组抗精神病药物使用者中 NMS 的发病率，并根据患者和抗精神病药物的特点描述了其变化。我们使用国家医疗补助数据（2004-2013 年）来确定开始抗精神病药物治疗的患者，并计算了抗精神病药物当前使用期间 NMS 的发生率。调整后的风险比（HRs）评估了患者和抗精神病药物特征对 NMS 风险的独立贡献。在 1032084 名患者中，有 131 例在 1472558 人年的抗精神病药物当前使用中发生 NMS，每 100000 人年 8.9 例。以下五个因素独立预测发病率增加：年龄 18-24 岁（HR [95%CI] = 2.45 [1.65-3.63]）、精神分裂症谱系和其他精神病性障碍（HR = 5.86 [3.16-10.88]）、神经发育障碍（HR = 7.11 [4.02-12.56]）、抗精神病药物剂量>200mg 氯丙嗪等效物（HR = 1.71 [1.15-2.54]）和第一代抗精神病药物（HR = 4.32 [2.74-6.82]）。每 100000 人年的 NMS 发病率从无上述因素者的 1.8（1.1-3.0）增加到有 4 或 5 个因素者的 198.1（132.8-295.6）。在将研究数据限制为第二代抗精神病药物、5-17 岁儿童和最近的 5 个日历年内进行敏感性分析后，结果基本不变。在接受抗精神病药物治疗的儿童和青少年中，五个因素独立确定了 NMS 发病率增加的患者：年龄 18-24 岁、精神分裂症谱系和其他精神病性障碍、神经发育障碍、第一代药物和大于 200mg 氯丙嗪等效物的抗精神病药物剂量。有 4 或 5 个这些因素的患者发病率是无这些因素的患者的 100 多倍。这些发现可以改善对 NMS 风险升高的儿童和青少年的早期识别，可能导致更早的发现和更好的结果。
