抗憂鬱劑與非類固醇抗發炎劑併用與顱內出血風險之探討

Abstract

摘要 背景：抗憂鬱劑與非類固醇抗發炎劑在臺灣皆是普遍使用的藥物。然而，抗憂鬱劑與非類固醇抗發炎劑的合併使用與顱內出血風險的關聯性仍不確定。 目的：評估抗憂鬱劑與非類固醇抗發炎劑使用對顱內出血的影響，以及探討不同種類的抗憂鬱劑與不同種類的非類固醇抗發炎劑使用對顱內出血的影響。 方法：使用臺灣全民健康保險研究資料庫，分析從2005年01月01日至2013年12月31日新使用抗憂鬱劑的病人，之後發生顱內出血的風險。利用嵌入型病例對照研究與病例交叉研究，探討抗憂鬱劑與非類固醇抗發炎劑對顱內出血的影響。本研究使用SAS 9.4 (SAS Institute Inc., Cary, North Carolina, USA)進行分析。 結果與討論：本研究納入2,945位顱內出血病人，並與之配對11,780位對照組。病人合併使用抗憂鬱劑與非類固醇抗發炎劑組與單獨使用抗憂鬱劑組比較，合併使用組在30天內會增加50%顱內出血的風險 (odds ratio: 1.53; 95% confidence interval: 1.31 - 1.80)。在非類固醇抗發炎劑分層分析中，使用非選擇性非類固醇抗發炎劑與抗憂鬱劑併用組相較選擇性COX-2抑制劑與抗憂鬱劑併用組有著更高的顱內出血風險。在抗憂鬱劑分層分析中，選擇性血清素再回收抑制劑、血清素與正腎上腺素回收抑制劑或是其他種類的憂鬱劑，與非類固醇抗發炎劑併用30天內均增加顱內出血風險。總結而言，無論使用哪一種對照組，合併使用抗憂鬱劑與非類固醇抗發炎劑有最高的顱內出血風險，單獨使用非類固醇抗發炎劑有次高的顱內出血風險，單獨使用抗憂鬱劑有最低的顱內出血風險。除此之外，30天內抗憂鬱劑與非類固醇抗發炎劑使用所造成的顱內出血風險最高 結論：非類固醇抗發炎劑在顱內出血中扮演重要的腳色，特別是非選擇性的非類固醇抗發炎劑。此之外，已使用抗憂鬱劑治療的病人再加上非類固醇抗發炎劑可能會增加顱內出血的風險。

ABSTRACT Background: Both the antidepressant drugs and non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed in Taiwan. However, association between the combination use of these two types of drugs and the risk of intracranial hemorrhage are still uncertain. Objective: First, to assess the effect of antidepressants and NSAIDs use on the risk of intracranial hemorrhage. Second, to evaluate the risk of intracranial hemorrhage by the different kinds of antidepressant and NSAID. Method: We applied National Health Insurance Research Database (NHIRD) to evaluate patients who were new antidepressant users from January 1, 2005, to December 31, 2013. We performed the nested case-control and case-crossover design to access the effect of antidepressants and NSAIDs use on the risk of intracranial hemorrhage. All statistical procedures were performed by the SAS software version 9.4 (SAS Institute Inc., Cary, North Carolina, USA). Result and Discussion: Among the study cohort, 2,945 patients were identified as eligible cases and matched to 11,780 controls. Patients receiving both antidepressants and NSAIDs had an 80% increased risk of intracranial hemorrhage compared to patients receiving antidepressants alone within 1 to 30 days before the index date (odds ratio=1.53; 95% confidence interval: 1.31 - 1.80). The risk of intracranial hemorrhage was found to be the highest in patients within 1 to 30 days before the index date. In stratified analyses, patients receiving non-selective NSAID/antidepressant combination had a higher risk of intracranial hemorrhage compared to patients receiving selective COX-2 inhibitor/antidepressant combination. Furthermore, an increased risk of intracranial hemorrhage with patients receiving SSRI, SNRI, or other types of antidepressants and NSAID combination as compared to antidepressant-only users within 1 to 30 days before the index date. To sum up, no matter what comparisons we chose, the highest risk of intracranial hemorrhage was in patients receiving antidepressant/NSAID combination, moderate in patients receiving NSAID alone, and lowest in patients receiving antidepressant alone. In addition, the risk of intracranial hemorrhage in each group was found to be highest within 1 to 30 days before the index date. Conclusion: NSAIDs use played an important role in the risk of intracranial hemorrhage, especially the non-selective NSAIDs. Furthermore, the addition of NSAIDs to antidepressant treatment may cause higher risk of intracranial hemorrhage.