台灣心房顫動併失智症患者之抗精神病藥品使用與缺血性腦中風之風險

Abstract

中文摘要 研究背景： 抗精神疾病藥品很普遍的用於治療失智症病人的行為及心裡異常症狀。近年來的一些抗精神疾病藥品與增加缺血性腦中風風險的研究，讓大家開始關注在這群失智症併有心血管疾病的病人中，使用抗精神疾病藥品的安全性。 研究目的： 1. 探討台灣心房顫動併失智症患者在個別抗精神病藥品的使用情形。 2. 探討抗精神病藥品對心房顫動併失智症患者缺血性腦中風風險的影響。 3. 比較第一代和第二代抗精神病藥品對心房顫動併失智症患者缺血性腦中風風險的影響。 4. 研究個別抗精神病藥品對心房顫動併失智症患者缺血性腦中風風險的影響。 5. 探討心房顫動併失智症患者使用抗精神病藥品的劑量反應關係。 研究方法： 本研究採用全民健康保險資料庫(National Health Insurance Research Database，NHIRD)進行觀察性回溯性世代研究。本研究以患有心房顫動併失智症病人作為研究對象。本研究利用 Cox proportional hazards model with time-varying covariates，以non-users作為對照組，分析使用抗精神疾病藥品是否會影響病人發生缺血性腦中風風險。本研究也利用Cox proportional hazards model去比較使用不同抗精神疾病藥品的中風風險。 研究結果： 於上述獲得之研究族群中, 使用第二代抗精神疾病藥品，尤其使用quetiapine 的心房顫動併失智症病人最為普遍，其次是使用haloperidol 及risperidone 的病人。研究發現使用抗精神疾病藥品的病人相對於未使用組有1.3倍的中風風險 (HR=1.293, 95% CI, 1.095-1.527)。第二代抗精神疾病藥品相對於第一代有統計上顯著較低的中風風險 (HR=0.763, 95% CI, 0.625-0.931)。相較於haloperidol, quetiapine (HR=0.689, 95% CI, 0.547-0.868)和risperidone (HR=0.755, 95% CI, 0.578-0.988)都有較低的統計顯著相關之中風風險。 結論： 本研究顯示在心房顫動併失智症病人中使用抗精神疾病藥品相對於未使用者有顯著增加的中風風險。第二代抗精神疾病藥品尤其是quetiapine相對於其他抗精神疾病藥品有較低中風風險。雖然此研究不能證明因果關係，但研究結果提供了更多中風風險證據，以協助臨床醫師選擇不同抗精神疾病藥品用於治療心房顫動併失智症病人的行為及心裡異常症狀。在不可避免使用抗精神疾病藥品的情況下, 此研究建議在這群具有較高中風風險的族群中使用較低劑量的quetiapine。

ABSTRACT Background: Antipsychotic drugs are commonly prescribed to elderly patients with dementia for the treatment of behavioral and psychological symptoms of dementia (BPSD). Evidence accumulated from several studies in recent years have raised strong concern about the association of antipsychotic use and increased risk of stroke in this population especially those with cardiovascular disease. Objectives: 1. Determine the prevalence of antipsychotic use in atrial fibrillation (AF) patients with dementia in Taiwan. 2. Investigate the effect of antipsychotic use on risk of stroke in patients with AF and dementia. 3. Compare the stroke risk between typical and atypical antipsychotic use in patients with AF and dementia. 4. Investigate the effect of individual antipsychotic use on the risk of stroke in patients with AF and dementia. 5. Evaluate the dose-response relationship of antipsychotic use in patients with AF and dementia. Methods: The present study conducted a retrospective cohort study with data from National Health Insurance Research Database (NHIRD). The cohort consisted of patients with AF and dementia. In non-users study, the risk of ischemic stroke associated with the use of antipsychotic drugs was evaluated by using an adjusted multivariate Cox proportional hazards model with time-varying covariates with non-users as the reference. The adjusted Cox regression model was also used for comparative risk between the class of antipsychotics and across individual antipsychotics. Results: Of the cohort, atypical antipsychotic especially quetiapine was the most commonly prescribed antipsychotic drugs followed by haloperidol and risperidone among patients with AF and dementia. Antipsychotic users were associated with almost 1.3 times increased risk of stroke (HR=1.293, 95% CI, 1.095-1.527) compared with non-users in patients with AF and dementia. Patients treated with atypical antipsychotic had a significantly lower risk of ischemic stroke (HR=0.763, 95% CI, 0.625-0.931) than typical antipsychotic. Compared with haloperidol, patients receiving quetiapine (HR=0.689, 95% CI, 0.547-0.868) and risperidone (HR=0.755, 95% CI, 0.578-0.988) were significantly associated with lower risk of ischemic stroke. Conclusion: The present study indicated that antipsychotic use was associated with increased risk of ischemic stroke compared to non-users in patients with AF and dementia. Atypical antipsychotic especially quetiapine had lower hazard ratios compared to other antipsychotics. Although the study cannot prove causality, the findings provide more evidence of the risk, assisting in decision making for clinicians considering antipsychotic for the treatment of BPSD in patients with AF and dementia. When the use of antipsychotic is inevitable, the study suggests prescribing quetiapine in lower possible dose in this population who possess the preexisting high risk of stroke.