基於健保資料庫數據分析抗組織胺藥物與失智症風險

研究目的：過敏性鼻炎患者經常使用H1抗組織胺藥物來緩解症狀，這類藥品具有抗膽鹼特性，與失智症風險相關。多項研究已指出，第一代抗組織胺藥物可能增加失智症風險，但對於第二代抗組織胺藥物是否同樣有此風險，尚無確切證據。此外，無論是第一代還是第二代抗組織胺藥物的累積劑量與失智症之間的關聯性也仍不明確。因此，本研究旨在透過健保資料庫，探討過敏性鼻炎患者使用抗組織胺藥物治療與失智症風險之間的關聯。研究方法及資料：本研究採用回溯性世代研究，資料來源為衛生福利部衛生福利資料科學中心之全人口檔。研究對象為2011至2017年間50歲以上確診過敏性鼻炎的患者，共714,052名，並追蹤至少三年，觀察失智症的發生情形。研究旨在探討第一代與第二代抗組織胺藥物與失智症風險的關聯性，並使用總和標準化每日劑量（Total Standardized Daily Dose, TSDD）將研究對象分成五組分析（未使用者、≤90、91-365、366-1095、>1095），以釐清整體及個別藥物的劑量與失智症風險之間的關係。研究結果：本研究結果顯示，無論是使用第一代或第二代抗組織胺藥物，患者在各個TSDD級距（≤90、91-365、366-1095、>1095）下，罹患失智症的風險均高於未使用者。在TSDD ≤90的情況下，使用第一代抗組織胺藥物的調整後相對風險比（Adjusted Hazard Ratio, aHR）為1.12（95% C.I. 1.08 - 1.16），而第二代抗組織胺藥物為1.10（95% C.I. 1.05 - 1.16）。TSDD介於91-365時，第一代抗組織胺藥物的aHR為1.29（95% C.I. 1.23 - 1.36），第二代則為1.23（95% C.I. 1.17 - 1.30）。在TSDD 366-1095範圍內，第一代抗組織胺藥物的aHR為1.52（95% C.I. 1.41 - 1.65），第二代為1.26（95% C.I. 1.18 - 1.34）。而TSDD大於1095時，第一代抗組織胺藥物的aHR達1.55（95% C.I. 1.32 - 1.81），第二代則為1.18（95% C.I. 1.06 - 1.31）。個別藥物中以Diphenhydramine 風險最高，當TSDD大於1095時aHR為為1.66（95% C.I. 1.12- 2.46）。結論與建議：過敏性鼻炎患者服用抗組織胺藥物會提高罹患失智症風險，且會隨著累積劑量增加而升高。與第二代抗組織胺藥物相比，服用第一代抗組織胺藥物罹患風險更高。臨床上治療過敏性鼻炎，選擇第二代抗組織胺藥物會是較好的選擇，但仍須謹慎注意其增加失智症之風險。

Objective：Patients with allergic rhinitis frequently use H1 antihistamines (AHs) to relief their symptoms. These medications with anticholinergic effect have been associated with an increased risk of dementia. Previous research has showed that first-generation antihistamines (FGAs) may elevate the risk of dementia, evidence regarding the potential impact of second-generation antihistamines (SGAs) remains inconclusive. Additionally, the relationship between the cumulative dosage of either FGAs or SGAs and dementia risk has yet to be fully elucidated. This study aims to investigate the association between AHs use and the risk of dementia in patients with allergic rhinitis, utilizing data derived from national health insurance database.Methods and Materials：This study used a retrospective cohort design, utilizing data from the comprehensive population database provided by the Health and Welfare Data Science Center of the Ministry of Health and Welfare. This study was focused on individuals aged over 50 years who were diagnosed with allergic rhinitis between 2011 and 2017, encompassing a total of 714,052 patients. These individuals were followed for a minimum of three years to monitor the incidence of dementia. The primary objective was to investigate the association between the use of FGAs and SGAs and the risk of dementia. To quantify drug exposure, the Total Standardized Daily Dose (TSDD) was used to categorize participants into five groups: non-users, ≤90, 91–365, 366–1095, and >1095 TSDD. This stratification aimed to elucidate the relationship between both cumulative drug dosage and dementia risk, considering overall and individual AHs use.Results：The result showed that the use of either FGAs or SGAs was associated with an increased risk of dementia across all TSDD intervals (≤90, 91–365, 366–1095, >1095) compared to non-users. For patients with TSDD ≤90, the adjusted Hazard Ratio (aHR) was 1.12 (95% CI: 1.08–1.16) for FGAs and 1.10 (95% CI: 1.05–1.16) for SGAs. When the TSDD was 91–365, the aHR was 1.29 (95% CI: 1.23–1.36) for FGAs and 1.23 (95% CI: 1.17–1.30) for SGAs. For TSDD 366–1095, the aHR increased to 1.52 (95% CI: 1.41–1.65) for FGAs and 1.26 (95% CI: 1.18–1.34) for SGAs. When TSDD >1095, the aHR for FGAs reached 1.55 (95% CI: 1.32–1.81), compared to 1.18 (95% CI: 1.06–1.31) for SGAs. Among individual AHS, diphenhydramine demonstrated the highest risk. For TSDD >1095, the aHR for diphenhydramine was 1.66 (95% CI: 1.12–2.46).Conclusion and Suggestion：The use of antihistamines (AHs) in patients with allergic rhinitis is associated with an increased risk of dementia, with the risk escalating as cumulative dosage increases. Compared to second-generation antihistamines (SGAs), first-generation antihistamines (FGAs) are linked to a significantly higher risk of dementia. Based on these findings, SGAs should be prioritized in the clinical management of allergic rhinitis to reduce cognitive risks and minimize side effects. However, careful consideration and monitoring are still necessary when prescribing SGAs to ensure safe and effective treatment.