不同血清素親和性抗憂鬱劑與上消化道出血之相關性研究

Variability of serotonin reuptake inhibition of antidepressants and the risk of upper gastrointestinal bleeding : retrospective cohort study

李彥潔(Yen-Chieh Lee)

指導教授 ： 賴美淑

國立臺灣大學/公共衛生學院/預防醫學研究所/碩士(2010年)

https://doi.org/10.6342/NTU.2010.10102

摘要

過去許多觀察性研究發現，選擇性血清素回收抑制劑 (selective serotonin reuptake inhibitors, SSRI)的使用，會增加上消化道出血住院之風險，其研究多侷限於西方國家，對於相關藥物(如非類固醇類抗發炎藥物NSAID/Coxib：選擇性或非選擇性，胃酸抑制劑PPI/H2RA)之交互作用亦未有一致定論。
本研究利用全民健保資料庫執行一回朔性世代研究，研究族群為2005-2006年同時合併精神科共病之抗憂鬱劑新使用者，依抗憂鬱劑之使用分類為三組：高、中、及低親和性抗憂鬱劑使用者，以使用低血清素親和性抗憂鬱劑之病患做為基準，分別於高和中血清素親和性抗憂鬱組別中配對propensity score相近者，成功於兩組中找到配對者即與其配對者一起納入配對後世代做結果分析；族群觀察始於藥物使用日，若發生上消化道出血住院，停藥，換別組藥物或研究結束日(2006-12-31)則觀察終止。
配對後世代各組各包含65133名抗憂鬱劑之新使用者，研究期間共有526例上消化道出血病例，分別占三組比例為0.34%、0.24%及0.23%，使用高及中親和性血清素抗憂鬱劑，對照於低血清素親和性使用者分別造成1.32(1.07-1.63) 及 1.13(0.90-1.41)之相對風險，且隨著血清素親和性的增加，隨著趨勢性上升(p=0.0081)，於敏感度分析(sensitivity analysis)中亦有相似結論，在次族群分析中，發現老年人及有上消化道出血病史之病患對高血清素親和性之抗憂鬱劑有較高之易感性，在藥物交互作用方面，則未見NSAID/Coxib或H2RA/PPI有風險調控之效果。
隨著對血清素親和性的增加，抗憂鬱劑之使用亦趨勢性增加上消化道出血之風險，臨床上開立處方應考量相關危險因子做個別評估，在本篇研究中未能發現胃酸抑制劑有風險調控之效益。

關鍵字

抗憂鬱劑 ； 上消化道出血 ； 世代研究 ； 血清素

並列摘要

Background
Previous studies have shown that use of selective serotonin reuptake inhibitions(SRIs) was associated with increased risk for upper gastrointestinal bleeding (UGIB). Our study aims to examine the association of UGIB with use of antidepressants with different serotonin affinity in psychiatric patients
Material and Method
We conducted a retrospective cohort study using the Taiwan National Health Insurance claims database. We identified 304,789 adults who initiated antidepressants during 2005-2006 and had a diagnosis of psychiatric diseases. Antidepressants were classified into 3 groups according to affinity to serotonin transporters (High, Intermediate and Low affinity_SRIs, HA_SRIs, IA_SRIs, LA_SRIs). Patients in LA_SRIs groups were matched in 1:1 fashion respectively to those in HA_SRIs and IA_SRIs groups with similar propensity score based on patients’ demographic, co-morbidities and medical utilization characteristics. Those successfully matched in 3 groups were followed from date of antidepressants initiation to first hospitalization for UGIB, drug discontinuation, shift of antidepressants from one group to another, or study end. We estimated crude and adjusted hazard ratios with a Cox proportional hazards model.
Result
In the propensity score matched cohort, 526 patients had experienced their first episode of hospitalization for UGIB, which accounts for 0.34, 0.24 and 0.23% in HA_SRIs, IA_SRIs and LA_SRIs group respectively. Use of HA_SRIs and IA_SRIs was associated with a HR of 1.32(1.07-1.63) and 1.13(0.90-1.41) for UGIB. Elderly and those with a history of upper GI bleeding were more susceptible. No effect modification was noticed with NSAID and acid suppressing agents
Conclusion
Use of high affinity serotonin reuptake inhibitors ,as compared with antidepressants with low serotonin transporter affinity, was associated with increased risk for admission for UGIB in psychiatric patients.

並列關鍵字

antidepressants ； selective serotonin reuptake inhibitors ； upper gastrointestinal bleeding ； cohort study ； serotonin

參考文獻

1.Longstreth GF. Epidemiology of hospitalization for acute upper gastrointestinal hemorrhage: a population-based study. Am J Gastroenterol. Feb 1995;90(2):206-210.

2.Boonpongmanee S, Fleischer DE, Pezzullo JC, et al. The frequency of peptic ulcer as a cause of upper-GI bleeding is exaggerated. Gastrointest Endosc. Jun 2004;59(7):788-794.

3.Harman JS, Edlund MJ, Fortney JC. Trends in antidepressant utilization from 2001 to 2004. Psychiatr Serv. May 2009;60(5):611-616.

4.Li N, Wallen NH, Ladjevardi M, Hjemdahl P. Effects of serotonin on platelet activation in whole blood. Blood Coagul Fibrinolysis. Nov 1997;8(8):517-523.

5.Wessinger S, Kaplan M, Choi L, et al. Increased use of selective serotonin reuptake inhibitors in patients admitted with gastrointestinal haemorrhage: a multicentre retrospective analysis. Aliment Pharmacol Ther. Apr 1 2006;23(7):937-944.