研究生: |
鐘盈姍 Chung, Ying-Shan |
---|---|
論文名稱: |
台灣兒童、青少年及年輕成人使用抗精神藥物之心血管代謝作用風險比較 Comparative Cardiometabolic Risk of Antipsychotics in Psychiatric Children, Adolescents and Young Adults: A Population-based Study in Taiwan |
指導教授: |
賴嘉鎮
Lai, Chia-Cheng Edward |
學位類別: |
碩士 Master |
系所名稱: |
醫學院 - 臨床藥學與藥物科技研究所 Institute of Clinical Pharmacy and Pharmaceutical sciences |
論文出版年: | 2017 |
畢業學年度: | 105 |
語文別: | 中文 |
論文頁數: | 175 |
中文關鍵詞: | 兒童與青少年 、年輕成人 、抗精神藥品 、心血管代謝風險 、主要心血管不良事件 |
外文關鍵詞: | children and adolescents, young adults, antipsychotics, cardiometabolic risk, major adverse cardiovascular events. |
相關次數: | 點閱:124 下載:6 |
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研究背景
隨著第二代抗精神藥物發展以及疾病診斷工具進步,越來越多年輕族群使用抗精神藥物。雖然藥物可有效改善病人的精神症狀,但有越來越多研究報告指出藥物有提高代謝症候群、心血管或腦血管事件的發生風險,而對於兒童與青少年、年輕成人族群的影響可能比成人族群更大。目前國內針對這些年輕族群相關的藥物安全資料以及長期評估報告付之闕如,臨床使用安全性仍然未知,亟需針對相關議題建立國人之本土使用安全數據。
研究目的
比較兒童及青少年、年輕成人使用不同抗精神藥物發生代謝失調事件與心血管不良事件之發生率、風險比以及危險因子探討。
研究方法
全民健保資料庫進行藥物比較風險之回溯性世代研究。納入2004年至2011年間,新使用口服抗精神藥品 (首筆處方日為指標日期) 之2歲到30歲精神疾患患者。排除過去糖尿病、高血壓、血脂異常、心血管疾病或相關用藥紀錄者,也排除腫瘤、先天疾病、多囊性卵巢症候群或懷孕者。欲觀察首要綜合心血管代謝事件包含:第二型糖尿病、高血壓、血脂異常以及主要心血管不良事件 (包含缺血性心臟病、缺血性腦中風與死亡),次要結果為個別第二型糖尿病、高血壓、血脂異常以及主要心血管不良事件。依據指標藥物分為九組 (haloperidol, sulpiride, risperidone, olanzapine, quetiapine, paliperidone, ziprasidone, aripiprazol以及amisulpride),分析病患年齡、性別、精神科診斷與精神相關用藥等病人基本特徵,追蹤並計算事件發生率,存活分析以多變項Cox比例風險模型校正干擾因子並估計風險比,以risperidone為對照組。
研究結果
本研究對象共納入79,641人,平均年齡20.4 (±標準差6.8) 歲,男性60%。平均年齡最小者為使用aripiprazole (16.3±6.6歲),最大則是使用quetiapine (23.8±21.歲)。指標藥品使用量之前四名為sulpiride (41%)、risperidone (20%)、haloperidol (12%) 以及quetiapine (11%)。精神診斷以焦慮症(42%)、思覺失調症(18%)、重度抑鬱症(16%) 以及雙極性疾患(13%)為主。經過9年觀察區間,首要綜合心血管代謝事件、第二型糖尿病、高血壓血脂異常以及主要心血管不良事件發生密度整體分別為32.2、3.3、20.5、5.5以及2.8 per 1000 person-years。對照 risperidone 組,在首要觀察結果中,olanzapine 組有較高的心血管代謝風險 (adjusted hazard ratio, 1.64; 95% CI, 1.21 - 2.22);在次要觀察結果中,olanzapine (1.80; 1.24 - 2.62) 與 haloperidol (1.54; 1.10 - 2.14 ) 有較高的高血壓風險; paliperidone (7.75; 2.35 - 25.6) 與 olanzapine (2.10; 0.99 - 4.44) 則有較高第二型糖尿病的風險。心血管代謝事件危險因子包含雙極性疾患、自閉症、焦慮症、物質濫用以及併用鎮靜安眠藥物。
研究結論
在臨床實務執行的情況下,相較於risperidone,患有精神疾患的兒童青少年以及年輕成人選用olanzapine有較高綜合心血管代謝風險;haloperidol有較高高血壓風險;paliperidone有較高第二型糖尿病風險;心血管代謝事件危險因子包含雙極性疾患、自閉症、焦慮症、物質濫用以及併用鎮靜安眠藥物,提供臨床醫師以及政策決策者作為用藥選擇的參考。
It has raised great concerns of cardiometabolic risk in young patients receiving antipsychotics recently. However, relevant evidences for Asian young population with psychiatric disorders remained limited. This study aimed to evaluate the comparative risk and risk factors of cardiometabolic events among psychiatric children, adolescents and young adults receiving antipsychotics.
We analyzed the Taiwan National Health Insurance Research Database from 2001-2012 and identified patients with psychiatric disorders aged 2-30 years newly received single oral antipsychotics. We defined a composite primary outcome of cardiometabolic events by using the diagnoses or medications of type 2 diabetes mellitus (T2DM), hypertension, dyslipidemia, and major adverse cardiovascular events (MACE). We performed Cox proportional hazard models to estimate the risk of cardiometabolic effects.
We identified a cohort of 79,641 patients with mean age of 20.4 (± 6.82) years and 60% of them were male. Most patients received sulpiride (41%), risperidone (31%), haloperidol (12%) and diagnosed with anxiety (42%), schizophrenia (18%), major depressive disorder (16%). The incidence rate of the cardiometabolic events was 32.2 per 1000 person-years. Compared to risperidone, we found patients receiving olanzapine (adjusted hazard ratio, 1.64; 95% CI, 1.21-2.22) had higher risk of cardiometabolic events. Patients receiving olanzapine or paliperidone had higher risk of T2DM; patients receiving haloperidol, olanzapine, or quetiapine had higher risk of hypertension comparing with risperidone. The findings warrant attentions on the patients to avoid unintended outcomes.
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