探討進行治療之慢性C型肝炎患者開立抗憂鬱藥物、鎮定安眠藥物處方與治療成效之相關性

Antidepressant and benzodiazepines are associated with the outcome of antiviral therapy in patients with chronic hepatitis C

蒲芊妤(Chien-Yu Pu)

指導教授 ： 白其卉

共同指導教授 ： 曹瓊文(Chiung-Wen Tsao)

臺北醫學大學/公共衛生暨營養學院/公共衛生學系暨研究所/碩士(2014年)

摘要

研究背景：慢性C肝患者(chronic hepatitis C, CHC)在干擾素治療期間常使用精神藥物用以減緩干擾素所產生之副作用以利完成治療。有研究指出血清素回收抑制劑(selective serotonin reuptake inhibitor, SSRI)類抗鬱劑、苯二氮泮類安眠鎮靜劑 (benzodiazepine, BZD)可以改善副作用如憂鬱、失眠。有研究指出SSRI會改變CHC患者干擾素治療的成效，但其相關機制尚不清楚。本研究嘗試觀察干擾素治療期間暴露於精神相關處方用藥是否改善CHC患者的治療效果及肝發炎指標。

材料與方法：本研究為病歷回溯之世代研究，收集民國92年11月至103年3月於新光醫院進行干擾素治療之CHC患者為378人。研究者進行病歷查閱並紀錄，內容包括基本特性資料、臨床療程紀錄及用藥資料、臨床檢驗報告等。暴露組定義為治療期間處方抗憂鬱劑或鎮靜安眠劑或是其他精神相關藥物。非暴露組定義為治療期間並無處方上述精神相關用藥者。追蹤時間點在基線、治療中第一個月、治療中第三個月、治療結束以及治療後六個月等五個時間點進行資料收集與分析。

結果：干擾素治療期間的CHC患者處方精神用藥佔44.77%。抗憂鬱劑用藥佔曾開藥者5.8%，BZD用藥則佔36.24%。雖然暴露於不分類之處方精神藥物者僅在第一個月時達到病毒反應(Early virological response)的比例顯著高於非暴露組(P=0.0305)，使用重複測量進行多變項校正後，暴露不分類之處方精神用藥者有顯著較高能力達到病毒反應(OR=1.37, P=0.0077)。將藥品種類分為暴露抗憂鬱劑(OR=2.47, P=0.0050)、BZD (OR=1.43, P=0.0013)後，也保持有顯著較高能力達到病毒反應。但是在有脂肪肝者、有肝硬化者、基線時有暴露精神處方用藥者達到病毒反應的顯著性就消失了。在多變項校正後，暴露不分類精神處方用藥者的麩草醋酸轉胺脢 (Glutamic oxaloacetic transaminase, GOT)比非暴露組多下降7.40 U/L (P=0.0398)，而麩丙酮酸轉胺脢(Glutamate Pyruvate Transaminase, GPT)則下降12.39 U/L (P=0.0518)。

討論：本研究結果顯示，不論是使用不分類精神藥物、抗憂鬱劑或BZD，相較於非暴露組，暴露組可達到較好的病毒反應，顯示協助完成治療即可提高達成病毒反應。

關鍵字

慢性C型肝炎 ； 干擾素治療 ； 病毒反應 ； 苯二氮泮類安眠鎮靜劑

並列摘要

Background: Interferon (IFN)-based therapy in patient with chronic hepatitis C (CHC) may cause psychiatric symptoms. Selective serotonin reuptake inhibitor (SSRI) and benzodiazepines are common to reduce the effect of fatigue, insomnia, depression in CHC patients. Several studies indicated SSRI improved the sustained virological response (SVR) in CHC patient, but the mechanism is not clear. The aim of this study was to evaluate the association of psychiatric medications and the effects of virological responses or liver damages among CHC patient during Peg-IFN therapy.

Method: This study was a retrospective cohort study. The consecutive CHC patients were treated with Peg-IFN combination with ribavirin at Shin Kong Wu Ho Su Memorial Hospital from 2003 to 2013. Totally, 378 patients were recruited. They were assessed at baseline, and followed at 1st month, 3rd month, end of treatment and the following 6th month after treatment. The exposure group was defined as those CHC patients had the treatment with related psychiatric medicine. Then we separated them into 2 subgroups: antidepressant or benzodiazepines. The nonexposure group was defined as these CHC patients who had never psychiatric medicine. All charts were reviewed. Basic characteristics, outpatient records and laboratory data were recorded.

Result: Among 378 CHC patients, 44.77% of the subjects ever used the psychiatric medicine during Peg-IFN therapy. Of them, 5.8% have prescribed antidepressant and 36.24% benzodiazepines. Among 4 time points, psychiatric medicine user had only a significantly increased proportion achieved varological response at 3rd month, compared with non-user during the Peg-IFN therapy. Psychiatric medicine user was benefited to achieved virological response (OR=1.37, P=0.0077) under the repeated analysis. Antidepressant and benzodiazepines also had the similar, effective virological responses (antidepressant: OR=2.47, P=0.0050. bezodiazepines: OR=1.43 P=0.0013). Those subjects with the fatty liver, liver cirrhosis or the usage of psychiatric medicine at baseline were worse in virological response than others. Besides, in multivariate analysis, psychiatric medicine user had more declined levels of GOT 7.40 U/L (P=0.0398) and GPT 12.39 U/L (P=0.0518).

Conlusion: Our results showed the psychiatric drugs had a significant improventment in achieving virological responses among CHC patients during Peg-IFN therapy.

並列關鍵字

chronic hepatitis C ； interferon-based therapy ； virological response ； benzodiazepine

參考文獻

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