抗精神病薬による認知症患者のリスク(Dementia patients at risk from antipsychotic drugs)

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2024-04-19 エディンバラ大学

認知症の患者によく見られる行動や心理的症状の管理に抗精神病薬が用いられますが、これらの薬剤は脳卒中や死亡リスクの増加と関連しているため、処方には注意が必要です。エディンバラ、マンチェスター、ノッティンガム、ダンディーの各大学の研究者による共同研究で、1998年から2018年にかけて認知症と診断された17万人以上のデータを基に、抗精神病薬の使用と健康リスクの関連が調査されました。この研究では、特に治療初週に肺炎のリスクが最も高く、6ヶ月間の治療で9人に1人が追加で肺炎を発症し、167人に1人が心筋梗塞を発症する可能性があることが示されました。

<関連情報>

認知症患者における抗精神病薬使用に関連する複数の有害転帰:集団ベースのマッチドコホート研究 Multiple adverse outcomes associated with antipsychotic use in people with dementia: population based matched cohort study

Pearl L H Mok, research fellow;   Matthew J Carr, research fellow;   Bruce Guthrie, professor;   Daniel R Morales, Wellcome Trust clinical research fellow;   Aziz Sheikh, professor;   Rachel A Elliott, professor;   Elizabeth M Camacho, senior research fellow;   Tjeerd van Staa, professor;   Anthony J Avery, professor;   Darren M Ashcroft, professor
The BMJ  Published: 17 April 2024
DOI:https://doi.org/10.1136/bmj-2023-076268

Fig 1

Abstract

Objective To investigate risks of multiple adverse outcomes associated with use of antipsychotics in people with dementia.

Design Population based matched cohort study.

Setting Linked primary care, hospital and mortality data from Clinical Practice Research Datalink (CPRD), England.

Population Adults (≥50 years) with a diagnosis of dementia between 1 January 1998 and 31 May 2018 (n=173 910, 63.0% women). Each new antipsychotic user (n=35 339, 62.5% women) was matched with up to 15 non-users using incidence density sampling.

Main outcome measures The main outcomes were stroke, venous thromboembolism, myocardial infarction, heart failure, ventricular arrhythmia, fracture, pneumonia, and acute kidney injury, stratified by periods of antipsychotic use, with absolute risks calculated using cumulative incidence in antipsychotic users versus matched comparators. An unrelated (negative control) outcome of appendicitis and cholecystitis combined was also investigated to detect potential unmeasured confounding.

Results Compared with non-use, any antipsychotic use was associated with increased risks of all outcomes, except ventricular arrhythmia. Current use (90 days after a prescription) was associated with elevated risks of pneumonia (hazard ratio 2.19, 95% confidence interval (CI) 2.10 to 2.28), acute kidney injury (1.72, 1.61 to 1.84), venous thromboembolism (1.62, 1.46 to 1.80), stroke (1.61, 1.52 to 1.71), fracture (1.43, 1.35 to 1.52), myocardial infarction (1.28, 1.15 to 1.42), and heart failure (1.27, 1.18 to 1.37). No increased risks were observed for the negative control outcome (appendicitis and cholecystitis). In the 90 days after drug initiation, the cumulative incidence of pneumonia among antipsychotic users was 4.48% (4.26% to 4.71%) versus 1.49% (1.45% to 1.53%) in the matched cohort of non-users (difference 2.99%, 95% CI 2.77% to 3.22%).

Conclusions Antipsychotic use compared with non-use in adults with dementia was associated with increased risks of stroke, venous thromboembolism, myocardial infarction, heart failure, fracture, pneumonia, and acute kidney injury, but not ventricular arrhythmia. The range of adverse outcomes was wider than previously highlighted in regulatory alerts, with the highest risks soon after initiation of treatment.

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