藥價政策對於處方行為及病人權益影響之研究— 以抗憂鬱劑為例

The impact of drug price policy on prescribing behaviors and patients right--Analysis of antidepressants

李宗蓁(Zong-Jhen Li)

指導教授 ： 高純琇

國立臺灣大學/醫學院/臨床藥學研究所/碩士(2007年)

https://doi.org/10.6342/NTU.2007.02144

摘要

研究背景：憂鬱症是一種高盛行率且失能程度嚴重的慢性疾病，藥物治療為憂鬱症之主要治療方式。第二代抗憂鬱劑特點為副作用小且療效和三環類抗鬱劑(tricyclic antidepressants, TCA)和單胺氧化酶抑制劑(monoamine oxidase inhibitor, MAOI)相當，故迅速成為臨床治療的第一選擇。健保局曾在2003年3月1日，單獨將第二代抗憂鬱劑fluoxetine 20 mg/tab之原廠藥(Prozac®)由每錠43.8元調降為18.7元，但其他第二代抗憂鬱劑僅微幅調降，因此造成抗憂鬱劑市場大變動。此種單一品項藥品大幅降價的措施，是否能有效達到健保控制藥費的目的？且對SSRI類及其他相關抗憂鬱劑的臨床使用的影響，一直受到醫藥界的關心與質疑。
研究目的：第一部份由醫學文獻資料庫搜尋第二代抗憂鬱劑療效相關文獻並比較第二代抗憂鬱劑各個藥物間及療效。第二部份針對使用fluoxetine病人進行研究，分析單一品項藥價大幅調降後對於醫師處方行為和病人權益的影響。
研究方法：第一部份利用系統性文獻回顧(systematic review)方法，分析比較第二代抗憂鬱劑藥物間的臨床療效。第二部份則利用向中央健康保險局申請的特殊主題健保資料庫檔「處方fluoxetine病患歸人檔(PMCDF)」為研究材料。由PMCDF資料庫中取得2003年1、2月連續兩個月處方Prozac®或fluoxetine學名藥大於7天，並且無處方其他第二代抗憂鬱劑的病人資料。分析在3月1日大幅調降Prozac®藥價之六個月內，Prozac®組或fluoxetine學名藥組病人的換藥情形，計算換藥率、續用率，進而分別分析換藥病人與續用病人的就醫次數、醫療資源耗用情況，並進行比較。
研究結果：由文獻搜尋找出Hansen RA et al(Ann Intern Med. 2005;143: 415-26.)為重鬱症綜合分析之代表性著作，並依據該篇的納入、排除條件，由所收集的文獻中，增加了5篇新的藥物和藥物直接作比較的研究，連同原收錄之46篇第二代抗憂鬱劑藥物和藥物直接作比較的文獻，共51篇文獻。综合分析結果顯示，fluoxetine vs.paroxetine (relative benefit(RB)= 1.05 (95% CI = 0.92 to 1.20))，兩組的最後反應率並沒有顯著的不同。Citalopram vs. escitalopram (RB= 1.06 (95% CI = 0.90 to 1.25))，也並沒有顯著的不同。Sertraline療效優於fluoxetine (RB= 1.10 (95% CI = 1.01to 1.20))。Venlafaxine療效優於fluoxetine (RB= 1.10 (95% CI = 1.01to 1.20))。
由PMCDF資料庫擷取出病人資料，Prozac®組5025位，fluoxetine學名藥組8739位，兩組的女性比例較高（56.75％、57.57％），平均年齡為47.0歲、48.8歲。兩組病人之換藥有90％以上皆為單一藥品品項的取代，Prozac®組換藥病人，以其他SSRI類藥物（50.86％）為主，且集中在區域醫院和醫學中心；fluoxetine學名藥組換藥病人，則以TCA+TeA類藥物（50.92％）為主，且集中在基層院所。Prozac®換藥組病人相較於同組續用病人，有較高之平均就醫次數(門診、精神科門診、急診、住院、精神科住院)。Fluoxetine學名藥組換藥病人相較於同組續用病人，在平均就醫次數，兩組無顯著差別。Prozac®組換藥病人相較於同組續用病人，有較高之醫療資源耗用。但fluoxetine學名藥組病人，卻呈現相反狀況；續用組病人相較於同組換藥病人，在門診、精神科門診有較高之醫療資源耗用，兩組無顯著差別。
結論：由第一部份的研究結果顯示，SSRI類藥物之間對於重鬱症的療效無顯著的差別。SSRI類的藥物和其他類藥物(SNRI, NaSSA, NDRI)的比較對於重鬱症的療效也無顯著差別。由第二部份的研究結果顯示，此種單一藥品藥價大幅調降措施，在初期（前三個月）有高於憂鬱症病人在常態下之換藥率。而且，所觀察到的換藥行為，有部分醫師係改為開立有較高藥價差利潤之高健保支付價之其他SSRI類藥物，對健保醫療資源的使用及分配，整體而言並非有益。此外，不同醫療機構層級別，有不同的健保藥品支付制度及進藥原則，也可能影響到醫師的處方行為，在基層院所有較多醫師可能因選擇使用簡表申請，而改採更低藥費之TCA+TeA類藥品。由病人及家屬的角度來看，單一藥品藥價大幅調降措施所可能導致的病人換藥，而有較多的就醫次數，都會產生一些有形、無形的負擔，進而影響到病人的權益。

關鍵字

藥價政策 ； 處方行為 ； 健保資料庫 ； 抗憂鬱劑 ； 選擇性血清促進素再吸收抑制劑

並列摘要

Background：Depression is a chronic mental disorder with high social burden due to its high prevalence rate and significant disability. Currently, drug therapy is the major strategy toward the depression treatment. Among those antidepressants, the second generation antidepressants quickly became the first drug choice in clinical therapy since they have less side effect profile and have similar efficacy when compared to tricyclic antidepressants (TCA) and monoamine oxidase inhibitor (MAOI). The reimbursement price of the 20 mg/tab branded fluoxetine (Prozac®) was reduced from NTD 43.8 to NTD 18.7 by the Bureau of National Health Insurance (BNHI) in March 1, 2003, but not to the other second generation antidepressants. It led to the redistribution of antidepressants market in Taiwan. Can this drug price reduction in deed achieve the goal to reduce the health insurance fee? Will this policy affect the usage of selective serotonin reuptake inhibitors (SSRI)?
Objective：Part I: To collect the papers related to the efficacy of second generation antidepressants and to compare the efficacy of them. Part II: Take fluoxetine as an example to analyze the impacts of dramatic price reduction in single SSRI antidepressant upon the doctor prescribing behaviors and patients benefits.
Methods：Part I: The clinical efficacy of second generation antidepressants was analyzed through a systematic review of literature searched from Medline. Part II: The Patients Medical Claim Dataset with Fluoxetine (PMCDF) in Taiwan provided by BNHI was used for data analysis. Patients prescribed with Prozac® or generic fluoxetine more than or equal to 7 days in both January and February of 2003 with no prescription of any other antidepressants at the same time were retrieved. The changes of antidepressant prescriptions were analyzed after the implementation of fluoxetine price reduction policy on March,1 2003. Drug change ratio and the continuous use ratio for patients in Prozac® group and in generic fluoxetine group were calculated. In both groups, patients under changed prescription or continuous use were further sub-grouped into 2 antidepressant utilization cohorts: (1) continuous use and (2) drug change. The total number of medical visit, medical resource consumptions of those patients were then compared between the two antidepressant utilization cohorts for Prozac® patient group and generic fluoxetine patient group.
Results：Part I: After literature search, the meta analysis for major depressive disorder (MDD), including 46 head to head clinical trials as indicated in the paper by Hansen RA et al. and 5 newly found head to head trials, were carried out. The rate of being a responder at study end did not differ significantly between fluoxetine and paroxetine (relative benefit,1.09 [95% CI, 0.97 to 1.21]). The efficacy of citalopram and escitalopram is similar. (relative benefit,1.06 [95% CI, 0.9 to 1.25]). A modest additional treatment effect (relative benefit, 1.10 [95% CI, 1.01 to 1.22]) for sertraline compared with fluoxetine; and modest additional treatment effect (relative benefit, 1.12 [95% CI, 1.02 to 1.23]) for venlafaxine compared with fluoxetine, were recognized. Part II: A total of 5025 patients and 8739 patients were included for Prozac® group and generic fluoxetine group, respectively. There were more woman in both two groups(56.75％ and 57.57％) in both groups. The mean age of these patients in two groups was 47.0 year old and 48.8 year old. In drug change cohorts of both groups, more than 90％ patients’ fluoxetine prescriptions were replaced by one other drug. The drug for replacement were mainly the SSRIs (50.86％) for Prozac® group and TCA+TeA (50.92％) for generic fluoxetine group. The prescription change patterns are different for both groups and depend on the type of medical institutions. In Prozac® group, the mean number of total medical visit in drug change cohorts was significantly higher than that in continuous use cohorts (general department, psychiatric department, emergency department, hospital admissions and psychiatric admissions). In generic fluoxetine group, there were no significant difference between the drug change cohorts and continuous use cohorts in terms of medical visits. In Prozac® group, the mean medical resource consumptions in drug change cohorts were significantly higher than those in continuous use cohorts. However, in generic fluoxetine group, the mean medical resource consumptions in drug change cohorts were significantly higher than those in continuous use cohorts with no significant difference.
Conclusions：Part I: In MDD, the clinical efficacy in SSRIs is similar and the clinical efficacy between SNRIs SNRI, NaSSA, NDRI and SSRIs is similar. Part II: The policy of dramatic drug price reduction for single agent had significantly affect the prescription switched for the first three months after the policy implemented. There was a high percentage of the antidepression prescriptions switching to the other SSRIs with higher drug price profit. This is not necessarily beneficial for the use and distribution of BNHIs’ medical resources. Besides, different type of medical institution, different drug payment system and different drug inclusion principles may also influence doctors’ prescribing behaviors. For instance, the fixed-drug daily payment may lead doctors in clinics to use drugs with lower prices such as TCA with TeA. For patients and their family, they may not be informed with the change of antidepressant prescription, even worse that, such change may result in more medical visits and hence have impact on patients’ benefits.

並列關鍵字

Drug price policy ； prescribing behaviors ； national health insurance database ； antidepressants ； selective serotonin reuptake inhibitor

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