抗精神病药物恶性综合征(NMS)是一种与抗精神病药物治疗相关的罕见急性不良反应。然而,关于NMS的风险和流行病学的数据很少。
这项研究的目的是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的相关性。
我们使用香港医院管理局的临床数据分析和报告系统数据库中的数据进行了一项基于人群的研究。病例在2004年1月1日至2017年11月30日期间首次诊断为NMS。病例交叉分析用于比较NMS诊断前30天(索引日期)和索引日期前91-120天的参考期的抗精神病药物暴露。为了调整抗精神病药物暴露的潜在时间趋势,我们从病例中取样,以匹配当前病例和未来病例,并进一步调整选择药物和急性医疗条件。
297,647名患者服用了抗精神病药,NMS发生率为0.11%。在病例交叉分析中包括的336例病例中,20(6%)在索引日期后30天内死亡;只有一例NMS被记录为主要死亡原因。与参考期相比,在诊断NMS前30天,患者更频繁地服用多种抗精神病药(15.8%vs26.8%;标准化平均差异[SMD]0.27)和短效可注射抗精神病药(3.6%vs13.7%;SMD0.37).在病例交叉中,抗精神病药物暴露的几率,根据时间趋势调整的案例交叉,根据时间趋势和潜在混杂因素分析调整后的病例交叉为8.00(95%置信区间3.42-18.69),5.88(2.46-14.04),和4.77(1.95-11.66)。
我们的研究结果表明,最近使用抗精神病药物与NMS有关。尽管仅针对案例的设计固有地控制着时间不变因素的混杂,无法完全排除与NMS表现相似的急性医学状况造成的残留混杂因素.
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.