摘要：研究背景：最近一大型研究指出抗憂鬱藥物及非類固醇抗發炎藥物併用時會增加顱内出血的風險。 由於目前關於此兩項藥品併用時的安全性研究相當有限，許多問題尚未釐清，如：併用時間長短及 併用藥品種類對於顱内出血風險的影響，無法為醫師進行臨床治療時提供相關證據做參考，因此需 進一步研究此兩種藥品併用時的安全性。研究目的：以不同研究設計模式（世代研究、病例對照設計、時間相依暴露模式）比較抗憂鬱藥物及 非類固醇抗發炎藥物併用時與單獨使用時的顱内出血風險，並評估老年人或是具有較高腦血管風險 的人併用此兩種藥時顱内出血的風險。研究方法：本實驗利用2005至2014年衛生福利資料科學中心的健康加值資料為資料來源，進行回 溯性世代研究及病例交叉研究。評估對象為20歲以上、初次診斷的憂鬱症患者，並排除在憂鬱症診 斷前有顱内出血病史、使用過精神相關藥物、或有其他精神疾病診斷之病人。各組間可能的干擾因 素將以傾向分數配對校正。Cox比例風險回歸模型及條件式羅輯斯回歸將用於比較使用單方及併用藥 品患者間的顱内出血風險。預期結果：本實驗結果將對於抗憂鬱藥物及非類固醇抗發炎藥物併用時是否會增加顱内出血的風險 提供進一步的證據，將有助於醫師評估此兩種藥品併用時的風險。
Abstract: Background: A recent large-scale study reported a significant increase in the risk of intracranial hemorrhage among patients treated with both antidepressants and NSAIDs compared to patients received antidepressants alone. However, present evidence does not suggest the use of either antidepressants or NSAIDs alone increases the risk of intracranial hemorrhage, and there is currently only one study available on this issue. In addition, many questions remain unanswered, including the long-term risk of combination treatment and the types of combination that might lead to the higher risk. Given that both antidepressants and NSAIDs are widely prescribed, a further investigation on the safety of the concurrent use of these two types of drugs is warranted.Objectives: 1) To compare the incidence of intracranial hemorrhage between patients with depression who received antidepressants alone and both antidepressants and NSAIDs, 2) to evaluate the association between the duration of the combination use of antidepressants and NSAIDs and the risk of intracranial hemorrhage, 3) to understand the risk of intracranial hemorrhage associated with the combination use of antidepressants and NSAIDs in potentially high-risk groups and the elderly, 4) to evaluate the risk of intracranial hemorrhage among patients with depression using a time-variant exposure approach, and 5) to compare the risk of intracranial hemorrhage between patients with depression who received NSAIDs alone and both antidepressants and NSAIDs.Method: This will be a nationwide claims-based study using the 2005-2014 Health and Welfare Data. Patients aged 20 years old or older who were newly diagnosed with depression will be included. Both cohort design and case-crossover design will be applied. Patients will be excluded if they had a history of intracranial hemorrhage, schizophrenia, bipolar disorder, or dementia, used psychotropic medications, or used injected antidepressants at any time during the study period. The cohort design will be used to compare the risk of intracranial hemorrhage between patients receiving antidepressant alone and combination of antidepressants and NSAIDs. Given that NSAIDs are often for intermittent or short-term use, the case-crossover design will be used to evaluate the association between intracranial hemorrhage and NSAID versus antidepressant/NSAID combination use. Propensity score matching technique will be applied to balance the baseline characteristics. Cox proportional hazards models and conditional logistic regressions will be used to generate the adjusted results. Several subgroup and stratification analyses will be performed to evaluate the risk of intracranial hemorrhage among the elderly or patients with high cerebrovascular baseline risk.Expected Results: Findings from this study will advance our knowledge about the risk of intracranial hemorrhage associated with the combination use of antidepressants and NSAIDs. By using the Health and Welfare claims data, our results will be highly generalizable to the population in Taiwan. Since little is known about the safety of combination use of antidepressants and NSAIDs, especially among the elderly, the study results will provide valuable information to the clinical practice. Results from this study will be turned into publications on peer-review journals and international conferences.
non-steroidal anti-inflammatory drugs
Health and Welfare Database