Department of Pharmacy, St. Peter's Hospital, Hamilton Health Sciences, Hamilton, ON, Canada.
School of Pharmacy, University of Waterloo, Waterloo, ON, Canada.
Int J Clin Pharm. 2021 Feb;43(1):212-219. doi: 10.1007/s11096-020-01135-9. Epub 2020 Sep 10.
Background Best practice guidelines recommend regular evaluation of antipsychotics in managing behaviours for dementia patients with a view to de-prescribing, given its significant mortality and adverse outcomes (Reus et al. in Am J Psychiatry 173(5):543-546, 2016, Deprescribing Guidelines and Algorithms in https://deprescribing.org/resources/deprescribing-guidelines-algorithms/ , 2019). The relationship between the dose of antipsychotic and the probability of discontinuation remains unknown in hospitalized dementia patients. Objectives This study aims to examine the relationship between high dose antipsychotic (greater than 62 mg chlorpromazine equivalent daily dose) and antipsychotics discontinuation in hospitalized dementia patients. Setting Specialized Dementia Behavioral Health Program in Hamilton, Ontario, Canada. Method A retrospective chart review was completed from August to December of 2019. A univariate logistic regression model was applied to antipsychotic doss (in chlorpromazine equivalent) and antipsychotic discontinuation outcome at 60 days (Narayan and Nishtala in Eur J Clin Pharmacol 73(12):1665-1672, 2017). A multivariant model was used to assess potential confounders, including other psychiatric medication exposure and Medicines Comorbidity Index (Luthra in J Gerontol Geriatr Res 4(260):2, 2015). Regression and dose-response models were utilized to identify the threshold dose (maximum daily dose). Main outcome measures Antipsychotic discontinuation at 60 days after the last dose. Results A total of 42 patients were eligible for outcome analysis. High dose antipsychotic was associated with worse discontinuation outcomes in both unadjusted (odds ratio, 0.09; 95% confidence interval, 0.02-0.37; p < 0.01) and adjusted generalized estimation equation models (odds ratio 0.65; 95% confidence interval, 0.59-0.72; p = 0.01). There were no statistically significant associations between baseline comorbidities (Medicines Comorbidity Index) (p = 0.68), mood stabilizer (p = 0.14), benzodiazepines (p = 0.93) and antidepressant exposure (p = 0.68) with antipsychotic discontinuation. The logistic regression model identified 40.7 mg of quetiapine, 1.7 mg of olanzapine and 0.51 mg of risperidone as the threshold dose, balancing sensitivity and specificity. The dose-response model also identified similar doses of 42 mg of quetiapine, 1.76 mg of olanzapine and 0.53 mg of risperidone. Conclusion The use of high dose antipsychotics is associated with worse discontinuation outcomes in hospitalized dementia patients. Therefore, our results suggest not exceeding a daily dose of 50 mg of quetiapine, 1.75 mg of olanzapine and 0.5 mg of risperidone when used for responsive behaviours and reassess the benefits and risks for each patient regularly.
最佳实践指南建议定期评估抗精神病药物在治疗痴呆患者行为方面的效果,以便减药,因为其具有显著的死亡率和不良后果(Reus 等人,《美国精神病学杂志》173(5):543-546, 2016,《Deprescribing Guidelines and Algorithms in https://deprescribing.org/resources/deprescribing-guidelines-algorithms/, 2019)。在住院痴呆患者中,抗精神病药物剂量与停药概率之间的关系尚不清楚。目的:本研究旨在研究高剂量抗精神病药物(大于 62mg 氯丙嗪等效日剂量)与住院痴呆患者停药之间的关系。地点:加拿大安大略省汉密尔顿的专门痴呆行为健康计划。方法:2019 年 8 月至 12 月进行了回顾性图表审查。应用单变量逻辑回归模型分析抗精神病药物剂量(以氯丙嗪当量表示)和 60 天停药结局(Narayan 和 Nishtala,《欧洲临床药理学杂志》73(12):1665-1672, 2017)。使用多变量模型评估潜在混杂因素,包括其他精神药物暴露和药物共病指数(Luthra,《老年学杂志:老年医学研究》4(260):2, 2015)。回归和剂量-反应模型用于确定阈值剂量(最大日剂量)。主要观察指标:末次剂量后 60 天的抗精神病药物停药。结果:共有 42 名患者符合结局分析标准。在未调整(比值比,0.09;95%置信区间,0.02-0.37;p<0.01)和调整后的广义估计方程模型(比值比 0.65;95%置信区间,0.59-0.72;p=0.01)中,高剂量抗精神病药物与停药结局较差相关。基线合并症(药物共病指数)(p=0.68)、心境稳定剂(p=0.14)、苯二氮䓬类(p=0.93)和抗抑郁药暴露(p=0.68)与抗精神病药物停药之间无统计学显著关联。逻辑回归模型确定了喹硫平 40.7mg、奥氮平 1.7mg 和利培酮 0.51mg 为阈值剂量,兼顾了敏感性和特异性。剂量-反应模型还确定了类似剂量的喹硫平 42mg、奥氮平 1.76mg 和利培酮 0.53mg。结论:在住院痴呆患者中,使用高剂量抗精神病药物与停药结局较差相关。因此,我们的结果表明,在治疗反应性行为时,使用的喹硫平、奥氮平和利培酮的日剂量不应超过 50mg、1.75mg 和 0.5mg,并且应定期重新评估每位患者的获益和风险。