自閉症譜系障礙兒童與青少年使用利培酮與阿立哌唑的暴力行為與心血管副作用之比較

研究目的：自閉症譜系障礙（Autism Spectrum Disorder, ASD）為神經發展障礙的一種，常伴隨社交互動困難、語言發展遲緩及重複性行為，根據中華民國自閉症基金會2023年的數據指出，自閉症的患病率為 1:36，並且全球自閉症患者估計約有2480萬人，已開發國家約有1.5%的兒童患有自閉症。這些數據表明自閉症的患病率一直在增加。除了傳統的行為症狀外，近年來的研究也顯示，自閉症患者可能會面臨更多的身體健康問題，尤其是心血管方面的風險，如心悸（palpitations）。本研究旨在比較阿立哌唑（Aripiprazole）與利培酮（Risperidone）於ASD兒童及青少年患者之療效與心血管安全性差異，進一步探討特定亞群的風險變化。研究方法與資料：本研究為回溯性觀察性研究，資料來源為美國大型真實世界醫療資料庫TriNetX。研究對象為年齡3至17歲、診斷為ASD之患者，排除具有癲癇、糖尿病病史或同時使用兩藥者。研究採用傾向性分數匹配（Propensity Score Matching, PSM）平衡兩組樣本之基線特徵，最終納入阿立哌唑與利培酮各12,453名使用者，進行Kaplan-Meier分析與Cox比例風險模型評估暴力行為與心悸等不良事件之發生風險。研究結果：結果顯示，兩組在控制暴力行為方面無顯著差異（HR=1.101，p=0.9729），顯示兩藥於行為療效具等效性。在心血管相關疾病方面，阿立哌唑使用者的心悸發生率顯著高於瑞必多組（1.4% vs.1.0%；HR=1.373，95% CI:1.093–1.724，p=0.0292）。亞組分析顯示，心悸風險在男性患者（HR=1.50，p=0.0023）及10歲以下兒童（HR=1.45，p<0.05）中更為顯著；此外，男性與合併焦慮症的患者使用阿立哌唑後，暴力行為風險亦明顯增加（HR=1.38，p<0.05）。結論與建議：我們的研究發現，阿立哌唑與利培酮在ASD患者行為症狀控制方面具相似療效，但阿立哌唑在心血管副作用風險，特別是心悸方面，顯著高於利培酮。建議臨床醫師在處方時，除評估行為療效外，亦應考量個別患者的心血管風險，並針對高風險亞群（如年幼、男性或合併焦慮症者）進行個體化風險評估與長期監測。未來研究亦應針對藥物與ANS失衡機轉進行更深入探討，以優化ASD患者的治療策略與生活品質。

Objective: Autism Spectrum Disorder (ASD) is a common neurodevelopmental disorder with a growing global prevalence, according to the 2023 data from the Autism Foundation of the Republic of China, the prevalence of autism is 1:36, with an estimated global population of 24.8 million individuals with autism. In developed countries, approximately 1.5% of children are affected by autism. These statistics highlight the rising prevalence of autism worldwide. While its core symptoms—such as social deficits, delayed language development, and repetitive behaviors—have been well-documented, emerging evidence suggests that individuals with ASD may also experience heightened physical health risks, particularly involving cardiovascular complications. Palpitations, a common but complex cardiovascular symptom, may be more prevalent in ASD patients due to both pharmacological side effects and underlying neurophysiological characteristics. This study aimed to compare the behavioral efficacy and cardiovascular safety of two widely used antipsychotic medications—aripiprazole and risperidone—in children and adolescents with ASD, with a focus on adverse events such as violent behavior and palpitations.Methods and Materials: We conducted a retrospective observational study using the TriNetX real-world medical database. Included ASD patients aged 3 to 17 years who were prescribed either aripiprazole or risperidone. Patients with a history of epilepsy, diabetes, or concurrent use of both medications were excluded. Propensity score matching (PSM) was employed to balance baseline characteristics between the two treatment groups, resulting in 12,453 patients in each cohort. Kaplan-Meier survival curves and Cox proportional hazards models were used to analyze the long-term risks of behavioral and cardiovascular adverse events.Results: There was no statistically significant difference between the two groups in terms of violent behavior incidence (HR = 1.101, p = 0.9729), indicating equivalent behavioral efficacy. However, the incidence of palpitations was significantly higher in the aripiprazole group compared to the risperidone group (1.4% vs. 1.0%; HR = 1.373, 95% CI: 1.093–1.724, p = 0.0292). Subgroup analyses revealed that the risk of palpitations was notably higher in male patients (HR = 1.50, p = 0.0023) and children under the age of 10 (HR = 1.45, p < 0.05). Furthermore, male patients and those with comorbid anxiety disorders treated with aripiprazole also demonstrated a significantly increased risk of violent behavior (HR = 1.38, p < 0.05).Conclusion and Suggestion: This study highlights that while aripiprazole and risperidone offer comparable effectiveness in managing behavioral symptoms in ASD, aripiprazole may be associated with an increased risk of cardiovascular side effects, particularly palpitations. Clinicians should be vigilant when prescribing aripiprazole, especially to high-risk subgroups such as young children, males, and those with comorbid anxiety disorders. These findings contribute to addressing existing gaps in the literature regarding ASD medication safety and support the development of safer, more personalized treatment strategies to enhance the overall quality of life for vulnerable ASD populations.