抗精神病藥物治療的臨床抉擇

Abstract

背景：臨床醫師在日常診療中常會遇到與用藥相關的臨床複雜難題，這些問題可能不只牽涉到藥效及安全性，也與藥價、生活品質等相關。成本效果分析及成本效用分析可能有助於解決這些問題，因為它們能將這些因素一起考慮進去。 研究目的：本研究將運用成本效果分析及成本效用分析來協助解決兩個重要臨床問題：（1）對於精神分裂症的急性激動，肌肉注射olanzapine好還是肌肉注射haloperidol加上lorazepam好？（2）對於失智症的急性激動或精神病症，傳統的抗精神病藥物好？還是新一代抗精神病藥物好？還是不用藥好？ 研究方法：將執行兩個研究來回答這兩個問題。在第一個研究，我們先做一個隨機控制試驗，比較肌肉注射olanzapine及肌肉注射haloperidol加上lorazepam的療效，然後將得到的參數，運用Markov決策模型加以分析，並進行成本效果分析及成本效用分析。在第二個研究，我們先從文獻搜尋老年失智症急性激動或精神病症時，用抗精神病藥物治療的相關資料及數據，將得到的參數運用Markov決策模型加以模擬，並進行成本效果分析及成本效用分析，比較三種治療策略：傳統抗精神病藥，新一代抗精神病藥物，安慰劑（假設安慰劑相當於非藥物的支持性治療）。 研究結果：總共67位精神分裂症或情感性精神分裂症病患參加第一個研究。隨機控制試驗發現兩組在藥效及安全性上無統計上差異。成本效果分析發現olanzapine比較貴，而且有效反應率沒有更高。就生活品質而言，成本效用分析發現olanzapine治療較能提高生活品質，比起肌肉注射haloperidol加上lorazepam，每增加一單位品質需要多付出4387.5元新台幣。第二個研究發現，用Markov決策模型模擬一年之後，傳統及新一代抗精神病藥物兩組在存活率上很接近，但比安慰劑組低，不過花費也比安慰組少。成本效用分析發現，傳統抗精神病藥物組效用最高，在模擬的一年追蹤中，安慰劑組的總生活品質最差，且花費最多。 討論：第一個研究雖然發現兩種治療療效相當，但以副作用而言，olanzapine組比haloperidol加上lorazepam組少。然而olanzapine的價格是haloperidol加上lorazepam的9倍。當考慮生活品質時，成本效用分析發現olanzapine治療較能提高生活品質，比起肌肉注射haloperidol加上lorazepam，其增加成本效用比為4387.5元新台幣。在不同國家的醫師也許會因此價格而有不同臨床決策。第二個研究發現傳統與新一代抗精神病藥物組的一年存活率相當，可能是因為雖然傳統藥物組有略高的整體死亡率，但其中風機會又略低於新一代組。安慰劑組有最高的一年存活率，但花費也很多。成本效用分析發現，傳統藥物組比其他兩組有的成本效用好。雖然安慰劑組有較低的中風機率，但也有較高激動的機率，這會降低生活品質。因此整體來說，最後還是會減低總生活品質調整人年。當對生活品質的參數進行敏感分析，仍然發現一致的結論。 結論：這兩個研究都支持使用成本效果分析及成本效用分析能協助臨床決策。當面對複雜臨床難題時，這些方法能協助臨床醫師較完整地評估問題，不但考慮藥效及安全性，也同時考慮藥價及生活品質。

Background: In real life, physicians frequently face complex clinical problems or even dilemmas in pharmacological treatment of patients. These problems may involve not only efficacy and safety, but also cost, quality of life and others. Cost-effectiveness analysis (CEA) and cost-utility analysis (CUA) may be helpful in this regard because these methods can take into consideration all relevant factors. Objectives: We aimed to apply the CEA and CUA method to help solve two important clinical questions: (1) “Intramuscular (IM) olanzapine versus intramuscular haloperidol plus lorazepam for the treatment of agitation in schizophrenia: which one to choose?” and (2)“Atypical and typical antipsychotic agents for the treatment of agitation/ psychosis in dementia: which to prescribe or not to prescribe?” Methods: We conducted 2 studies to answer the 2 questions. In study one, we implemented a randomized controlled trial (RCT) comparing IM olanzapine versus IM haloperidol plus lorazepam in the treatment of acute agitation of schizophrenia, and then performed Marcov decision model, CEA and CUA based on data from the RCT. In study two, we searched relevant information from literature regarding the antipsychotic treatment of agitation/ psychosis in patients with dementia, and performed Marcov decision model, CEA and CUA on 3 different strategies: typical antipsychotic treatment, atypical antipsychotic treatment and placebo (assumed to be equivalent to non-pharmacological supportive care). Results: In study one, a total of 67 agitated patients with schizophrenia or schizoaffective disorder were enrolled. The RCT showed that both treatments were not significantly different in terms of efficacy and safety measurements. Regarding response, CEA showed the olanzapine treatment was dominated by haloperidol plus lorazepam treatment because the former had higher cost and marginally lower response proportion. However, in terms of quality, CUA showed olanzapine treatment had higher quality of life and the incremental cost was 4387.5 NTD per utility-gained compared to the haloperidol plus lorazepam treatment. Study two found that the 2 antipsychotic treatments were very similar in total survival life-years in one-year follow-up, but the survival life-years were shorter than that in the placebo group. However, the 2 antipsychotic treatment groups also spent much less money than the placebo group. CUA showed that both atypical antipsychotic treatments and placebo treatment were dominated by typical antipsychotic treatment. After one-year follow-up, the placebo group had worst quality of life and biggest expenditure. Discussion: Study one found the 2 treatments are similar in efficacy, but IM olanzapine treatment seems to be better than IM haloperidol plus lorazepam treatment because of its relatively lower incidence of significant adverse drug reactions. However, the cost of IM olanzapine is about 9 times as that of haloperidol plus lorazepam treatment. When quality of life is considered, IM olanzapine treatment has higher utility and the incremental cost-utility ratio (ICUR) indicates one extra utility can be gained at the price of 4387.5 NTD for one time intervention. Depending on economical status and government policy, physicians of different countries may make different decisions. Study two showed the 2 antipsychotic treatments were similar in terms of one-year survival. This might be due to that facts that, compared with typical antipsychotic treatment, the atypical antipsychotic treatment was associated with slightly lower all-cause mortality, but also slightly higher risk of cerebrovascular accidents (CVAs). Compared with the 2 antipsychotic treatment groups, the placebo treatment group had the biggest expenditure and longest survival after one-year follow-up. When we took quality of life into consideration, both placebo and atypical antipsychotic treatment were dominated by typical antipsychotic treatment. This was demonstrated by the CUA. Although the placebo group had lower risk for CVAs, it also had higher risk for agitation (higher probability of “non-response”), which would impair the quality of life significantly. Therefore, the overall quality adjusted life-years (QALY) of the placebo group was still low. A sensitivity analysis on the assigned utility of “non-responder” also showed consistent findings that the placebo group had the lowest QALY during one-year follow-up. Conclusions: These 2 studies provide support to the use of CEA and CUA in making clinical decisions. By using these methods, physicians can examine a clinical complex treatment issue in a more comprehensive manner, not only considering efficacy and safety, but also taking cost and quality of life into account.