研究背景：雖然當欣流（Montelukast成分，商品名Singulair）此非類固醇成分的氣喘維持型藥物於1998年在美國上市後，使用欣流的氣喘患者日漸增加，但隨著越來越多關於欣流導致神經精神類及自殺事件發生的報告，以及探討這兩者之間相關性的研究出現，欣流的安全性受到了疑慮。美國食品及藥物管理局（FDA）評估了多方報告、臨床數據及觀察性研究結果後，最終在2020年將欣流相關風險升級為盒裝警告，以加強患者及醫護人員對於此相關性的認識。在國外已有數篇探討欣流與神經精神類事件及自殺事件的觀察性研究，但是欣流於2000年在台灣上市後，鮮少有針對欣流與此兩種事件之間相關性進行探討的研究。
研究目的：本研究欲探討氣喘患者的欣流使用比例與趨勢，以及探討不同年齡層的氣喘患者使用欣流對於神經精神類事件或自殺事件發生的風險。
研究方法：首先，分析2004年至2017年期間，氣喘患者的欣流使用比例年度趨勢變化。接著，使用巢式病例對照研究分別探討0-59歲使用欣流的氣喘患者，在2005年至2017年的研究期間，首次經由急診或住院診斷發生之神經精神類事件或自殺事件的風險。每個病例以1：4的比例在尚未發生事件且存活的氣喘患者中，配對相同的性別、氣喘診斷年度和出生年度，同時給予相對應的index date。配對後，回顧病例和對照個案在index date前365天的氣喘藥物處方紀錄、就醫、共病情形等。在進行事件發生的風險估計時，納入社會經濟地位、身體健康狀態和氣喘嚴重程度相關因子進行校正。
研究結果：2004年至2017年，使用欣流的氣喘患者呈現逐年上升的趨勢。在2005年至2017年研究期間，診斷發生神經精神類事件的部分共納入10157名病例，經校正干擾因素後，0-59歲有欣流處方紀錄者發生事件的風險是沒有紀錄者的1.16倍（p值<.0001），但沒有發現劑量效應關係，且進一步發現年齡層越低的氣喘患者發生事件的風險越高。在自殺事件的部分共納入531名病例，同樣經校正干擾因素後，0-59歲有欣流處方紀錄者發生自殺的風險是沒有紀錄者的1.28倍（p值=0.0994）。
結論：本研究發現使用欣流可能會增加神經精神類事件發生的風險，其中又以年輕族群效應較大，但欣流對自殺發生的風險目前尚不明確。因此，醫護人員應當更加注意使用欣流作為氣喘治療藥物的氣喘患者，且在開立處方時應該要告知患者以及其照顧者，使用欣流可能會導致的相關神經精神類副作用，以加強對於症狀的認知與監測。

Background: Montelukast (Singulair), a non-steroidal asthma maintenance drug, has been available in the United States since 1998, the number of asthma patients who used montelukast have increased gradually, as the increase of the adverse reactions reports about the neuropsychiatric events or suicide resulting from montelukast, montelukast’s safety has been in dount. After evaluating a variety of reports, clinical data and observational research results, the U.S. Food and Drug Administration (FDA) finally upgraded the risks related to montelukast to a boxed warning in 2020 to strengthen patients and medical staff's’ knowledge of this association. There have been several observational studies about the neuropsychiatric events and suicide resulting from montelukast in foreign countries since 1998. However, after montelukast has been available in Taiwan since 2000, there are still very few studies explore the association between montelukast and neuropsychiatric events and suicide so far.
Objective: To explore the proportion and the trend of asthma patients with montelukast in use, and further evaluate the risks of asthma patients with montelukast in use experiencing neuropsychiatric events or suicide in different age groups.
Methods: Firstly, we analyzed the annual trend of the proportion among asthma patients with montelukast in use from 2004 to 2017. Secondly, a nested case-control study was used to explore the risks of asthma patients with montelukast in use who were diagnosed as new-onset neuropsychiatric events or suicide by emergency department or hospitalization from 2005 to 2017. Cases were matched up to 4 controls on sex, the year of diagnosis as asthma and the year of birth from asthma patients who were still alive and had not experienced events, and the corresponding index date was given at the same time. After matching, we reviewed asthma drugs prescriptions, medical care and health condition in 365 days before index date among all cases and controls. Covariates in the adjusted model included sociodemographic factors, health condition and measures of asthma severity.
Results: The proportion of asthma patients with montelukast in use was rising from 2004 to 2017. In total, 10157 cases with neuropsychiatric events and 531 cases with suicide were included. Patients aged 0-59 years old who experienced a new-onset neuropsychiatric events had 1.16 times the odds of having been prescribed montelukast, compared with controls (p <.0001), however, we did not find the dose-response relationship. Furthermore, we also found that the younger patients get higher risk than older patients. In addition, patients aged 0-59 years old who experienced a new-onset suicide had 1.28 times the odds of having been prescribed montelukast, compared with controls (p=0.0994).
Conclusions: The research found taking montelukast may increase the risk of experiencing neuropsychiatric events, especially in younger patients. However, the risk to suicide was not clear for now. Therefore, medical staffs should pay more attention to those patients who are montelukast in use.

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