Department of Pharmacology and Pharmacy, Centre for Safe Medication Practice and Research, The University of Hong Kong, Office 02-08, 2/F Laboratory Block, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China.
Global Medical Affairs, Merck Research Laboratories, Shanghai, China.
CNS Drugs. 2020 Nov;34(11):1165-1175. doi: 10.1007/s40263-020-00767-9. Epub 2020 Oct 3.
Neuroleptic malignant syndrome (NMS) is a rare and acute adverse drug reaction associated with antipsychotic therapy. However, few data on the risk and epidemiology of NMS are available.
The aim of this study was to ascertain the incidence risk and all-cause mortality of NMS associated with antipsychotic use, and to assess the association of recent antipsychotic exposure and NMS.
We did a population-based study using data from the Hong Kong Hospital Authority's Clinical Data Analysis and Reporting System database. Cases had a first diagnosis of NMS between 1 January 2004 and 30 November 2017. A case-crossover analysis was used to compare antipsychotic exposure 30 days before the diagnosis of NMS (index date) and a reference period 91-120 days before the index date. To adjust for potential time trends in antipsychotic exposure, we sampled from cases to match current cases and future cases, and further adjusted for select medications and acute medical conditions.
297,647 patients were prescribed antipsychotics, and the incidence risk of NMS was 0.11%. Of the 336 cases included in the case-crossover analysis, 20 (6%) died within 30 days after the index date; only one case had NMS recorded as the primary cause of death. When compared with the reference period, cases were more frequently prescribed multiple antipsychotics (15.8% vs 26.8%; standardized mean difference [SMD] 0.27) and short-acting injectable antipsychotics (3.6% vs 13.7%; SMD 0.37) during the 30 days prior to the diagnosis of NMS. Odds ratios for antipsychotic exposure in the case-crossover, case-crossover adjusted for time trend, and case-crossover adjusted for time trend and potential confounders analysis were 8.00 (95% confidence interval 3.42-18.69), 5.88 (2.46-14.04), and 4.77 (1.95-11.66).
Our results suggest that recent use of antipsychotics is associated with NMS. Although a case-only design inherently controls for confounding by time-invariant factors, residual confounding by acute medical conditions with similar presentations to NMS cannot be fully excluded.
神经阻滞剂恶性综合征（NMS）是一种罕见的、与抗精神病药物治疗相关的急性药物不良反应。然而，目前关于 NMS 的风险和流行病学数据有限。
本研究旨在确定与抗精神病药物使用相关的 NMS 的发病率风险和全因死亡率，并评估近期抗精神病药物暴露与 NMS 的关系。
我们使用香港医院管理局临床数据分析及报告系统数据库中的数据进行了一项基于人群的研究。病例的 NMS 首次诊断时间为 2004 年 1 月 1 日至 2017 年 11 月 30 日。采用病例交叉设计比较 NMS 诊断前 30 天（索引日期）和索引日期前 91-120 天的抗精神病药物暴露情况。为了调整抗精神病药物暴露的潜在时间趋势，我们从病例中抽取样本，匹配当前病例和未来病例，并进一步调整了选择的药物和急性医疗状况。
297647 名患者被处方了抗精神病药物，NMS 的发病率风险为 0.11%。在纳入病例交叉分析的 336 例病例中，有 20 例（6%）在索引日期后 30 天内死亡；仅有 1 例病例的 NMS 被记录为主要死因。与参考期相比，病例在 NMS 诊断前 30 天内更频繁地服用多种抗精神病药物（15.8%比 26.8%；标准化均数差值 [SMD] 0.27）和短期注射用抗精神病药物（3.6%比 13.7%；SMD 0.37）。病例交叉、病例交叉调整时间趋势和病例交叉调整时间趋势和潜在混杂因素分析的抗精神病药物暴露比值比分别为 8.00（95%置信区间 3.42-18.69）、5.88（2.46-14.04）和 4.77（1.95-11.66）。
我们的结果表明，近期使用抗精神病药物与 NMS 有关。尽管病例仅设计从本质上控制了时间不变因素引起的混杂，但仍不能完全排除具有类似 NMS 表现的急性医疗状况引起的残余混杂。
