台灣美沙冬替代療法之成效評估

Evaluation on the Effectiveness of Methadone Maintenance Treatment Program in Taiwan

李欣雅(Hsin-Ya Lee)

指導教授 ： 李志恒

高雄醫學大學/藥學院/藥學研究所/博士(2012年)

摘要

美沙冬維持療法計畫（Methadone Maintenance Treatment Program, MMTP）在台灣始於2005年之減害計畫（Harm reduction），而減害計畫執行過程中，可能包含其他影響人類免疫缺乏病毒（Human Immunodeficiency Virus, HIV）控制的變數，因此，我們想要先探討減害試辦計畫（Pilot Harm Reduction Program, PHRP）實施對於HIV發生率控制之影響。我們發現實施PHRP的地區及時間，對於HIV發生率的確是呈現保護作用，而HIV強制篩檢及衛生教育實為有效控制HIV所不可或缺的因素。而MMTP卻成為HIV發生率的危險因子，此外，MMTP的政策執行也耗費大量的國家醫療成本，因此，也促使我們想要進一步探究MMTP的成效及相關影響因子。
本研究共招募178位MMTP個案。先透過系統性方式連結健保資料庫、疾管局美沙冬給藥系統、病歷資料及面對面會談以評估MMTP個案藥物交互作用及藥物併用的情形，研究結果顯示個案於MMTP可能會併用一些可能會影響methadone作用的藥物，而可能會導致withdrawal症狀、增加呼吸抑制的危險及導致嚴重QT interval prolongation。
本研究進一步利用橫斷式研究方式，探討台灣美沙冬個案之美沙冬藥物交互作用、共併疾病、血中美沙冬濃度、維持劑量、CYP 2B6、CYP 2C19、ABCB1基因多型性與治療成效（非法濫用鴉片類藥物）之間關係。為了要排除美沙冬與HIV抗病毒藥物之間嚴重的藥物交互作用，本研究僅招募非HIV個案進入本研究，我們利用stepwise multiple linear regression方式分析，結果顯示methadone維持劑量、CYP 2B6 A785G（A/G及G/G）及ABCB1 G2677T（G/T及T/T）對於methadone血中濃度的影響呈現正向關係。而進一步使用multiple logistic regression with stepwise selection探討MMTP治療的影響變因，也就是對於非法鴉片類物質濫用的情形，當個案帶有ABCB1 G2677T（G/T及T/T）時，對於非法鴉片類使用的情形呈現保護的作用，但是曾經有精神疾病、酒精濫用歷史、HCV感染、CYP2B6 A785G（A/G及G/G）對於非法鴉片類濫用的情形則呈現危險的因子。
1年長期追蹤的結果則顯示參與MMTP個案對於感染性指標，如：HIV、HBV、HCV及梅毒轉陽率並沒有惡化的趨勢；鴉片類物質及安非他命濫用的情形則是在第6個月的評估改善許多；在MMTP的留治情形至第12個月則為64.0 ％，較高的使用劑量可能可以增加個案於MMTP的留治率，但是低劑量的使用對於服藥順從性則有強烈關係。
透過多方面探討影響MMTP成效之相關原因，藉由對於MMTP個案的特性了解，於未來將可以對於MMTP治療提供有效的治療對策，以減少醫療資源的浪費。

關鍵字

減害計畫 ； 美沙冬替代療法 ； 美沙冬藥物交互作用 ； 單核苷酸多型性

並列摘要

In 2005, a national harm reduction program including a methadone maintenance treatment program (MMTP) was implemented in Taiwan. There were variables associated with HIV incidences among a national pilot harm reduction program (PHRP). We conducted this study to evaluate the effectiveness of harm reduction measures on HIV control. The result showed that the implementation of the PHRP did result in a significant difference in the monthly HIV incidence between areas with and without the PHRP, and HIV testing and education were essential for effective HIV control upon implementing the PHRP. However, a MMTP not only contributed to a higher HIV incidence and the implementation of a MMTP but also may cost huge national health care resources. Thus, these controversial results motivated us to investigate the effectiveness and the variables of a MMTP in Taiwan.
There were 178 patients in this study. First, we used credible data sources, including the National Health Insurance (NHI) database, face-to-face interviews, medical records, and methadone computer databases to determine the prevalence and clinical characteristics of MDIs and comedications. The results showed that clinically significant MDIs included withdrawal symptoms, severe QTc prolongation effect, and additive CNS and respiratory depression.
Furthermore, we used cross-sectional method to investigate the associations among methadone-drug interactions (MDIs), comorbidity diseases, substance abuse history, methadone maintenance doses, methadone plasma concentrations, CYP 2B6, CYP2 C19, and ABCB1 gene polymorphism, and illicit opioid consumption. To decrease the pharmacokinetic effects of antiretroviral drugs on methadone, we recruited non-HIV MMTP clients in this study. The results of our study demonstrated that the methadone maintenance dose, CYP2B6 785G allele, and ABCB1 2677T allele have positive effects on the methadone plasma concentrations. Furthermore, a positive indicator of the treatment responses is the ABCB1 2677T allele. In contrast, patients with HCV co-infection, alcohol problems, and psychiatric diseases may have a negative response to treatment.
In addition, the results showed that HIV, HBV, HCV, and syphilis seroconversions did not deteriorate after one year follow-up assessment. Opiate drug and amphetamine abuse among MMTP patients improved at 6th month than 1st month. The retention rate in MMTP decreased from 100 % at 1st month to 64.0 % at 12th month, and patients used higher methadone maintenance doses may increase the retention rate. However, patients used lower doses represented higher adherence to MMTP.
In summary, we used different variables, regarding pharmacogenetic factors, substance abuse history, methadone maintenance doses, methadone plasma concentrations, and methadone-drug interactions, to investigate the effectiveness of a MMTP. To understand the characteristics of MMTP patients can assist physicians in defining the efficient treatment strategy and can decrease the waste of medical care resources.

並列關鍵字

Harm reduction ； Methadone Maintenance Treatment Program ； Methadone-Drug Interactions ； Single Nucleotide Polymorphism

參考文獻

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