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系統識別號 U0007-0607201101311000
論文名稱(中文) 臺灣老年失智症病人之行為與精神症狀的用藥管理與照顧: 回溯性研究
論文名稱(英文) Medication Management and Care for Geriatric Patients with Behavioral and Psychological Symptoms of Dementia in Taiwan: A Retrospective Study
校院名稱 臺北醫學大學
系所名稱(中) 藥學研究所
系所名稱(英) Graduate Institute of Pharmacy
學年度 99
學期 2
出版年 100
研究生(中文) 林嘉恩
研究生(英文) Chia-En Lin
電子信箱 JohnLin1207@gmail.com
學號 M301098025
學位類別 碩士
語文別 英文
口試日期 2011-06-23
論文頁數 72頁
口試委員 委員-陳榮基
委員-闕壯卿
共同指導教授-胡朝榮
指導教授-何意
中文關鍵字 抗憂鬱劑  抗精神病劑  失智症的行為與精神症狀  實證醫學  老年醫學  非核准仿單標示用法  精神科藥物  鎮靜安眠劑 
英文關鍵字 Antidepressants  antipsychotics  behavioral and psychological symptoms of dementia (BPSD)  evidence-base medicine  geriatric medicine  off-label use  psychotropic drugs  sedative/hypnotic drugs 
學科別分類
中文摘要 研究背景:有鑑於第一代與第二代抗精神病劑可能增加伴隨有行為與精神症狀的失智症病人罹患心血管疾病與吸入性肺炎之機率,因而提高致死風險,自2003年起,美國食品藥物管理局陸續針對此問題發出警訊。儘管多次嚴重警訊,抗精神病劑於失智症病人的處方率仍高居不下。目前,加拿大失智症病人的抗精神病劑處方率相對於其他國家低,但在警訊之後處方率並無下降 (2000 [1.1%]vs.2007 [1.8%])。至於美國 (14.93%-17.7%) 與臺灣 (48.8%) 失智症病人的抗精神病劑處方率更遠高於加拿大。研究目的:藉由臺灣全民健康保險研究資料庫與臺北醫學大學教學醫院失智症病人的病歷回溯,分析臺灣老年失智症病人各種精神科用藥的處方率。此外,基於病人用藥安全與實證醫學,透過文獻回顧對臺灣伴隨有行為與精神症狀的失智症病人提出一套治療與照顧原則來改善臺灣失智症病人的用藥安全與臨床處置。研究方法:本研究為一個回溯性研究並分為兩部分。第一,全民健康保險研究資料庫的百萬人歸人檔分析部分,本研究擷取2004至2006年連續追蹤三年的1,449位六十五歲以上的失智症老人資料,分析其三年間每年的精神科用藥處方率。第二,病歷回溯部分,本研究亦回顧2005年至2011年間,來臺北醫學大學教學醫院的精神科或神經內科門診且大於65歲的70位失智症病人的精神科用藥處方率。研究結果:全民健康保險研究資料庫分析部分,1,449位失智症病人中發現抗精神病劑 (2004 [41.6%]; 2005 [43.0%]; 2006 [40.2%], p > 0.05) 的處方率皆高達40%以上,且在三年間沒有顯著改變。鎮靜安眠劑的處方率亦超過50% (2004 [59.4%]; 2005 [56.2%]; 2006 [50.7%], p < 0.05) ,其中又以 benzodiazepine 類的處方居多(benzodiazepine 類的處方率:49.9%-50.2%)。抗癲癇劑於三年間的處方率(7.6%-8.2%) 亦無改變。然而,抗憂鬱劑的處方率 (2004 [33.8%]; 2005 [30.6%]; 2006 [27.1%], p < 0.05) 在這三年間有顯著下降。此外,在這三年間,有24%-29% 的失智症病人沒有使用任何精神科用藥。教學醫院失智病患病歷回溯的部分,70位失智症病人的精神科藥物處方率分別為抗精神病劑75.7%,鎮靜安眠劑58.6%,抗憂鬱劑52.9%與抗癲癇劑5.7%。只有7%的失智症病人沒有接受任何精神科用藥處方。研究結論:本研究顯示美國食品藥物管理局所發佈的警訊對臺灣醫生開立非仿單核准適應症的抗精神病劑於失智症病人的情形並無改善。另外,教學醫院使用抗精神病劑來治療失智症病人的行為與精神症狀的處方率遠比全民健康保險研究資料庫分析的結果高出將近一倍;推測可能的原因是來醫院就診的失智症病人的行為與精神症狀的病情相對較嚴重,與兩資料庫的規模大小程度不同所造成的誤差。抗精神病劑只可短期用來處置伴隨有行為與精神症狀失智症病人的激躁,妄想與幻覺等症狀,但目前文獻與治療指引仍不建議長期使用。醫師與藥師應盡告知病患與照顧者非仿單適應症的抗精神病劑用於失智症病人會增加死亡率。有鑑於病人用藥安全與生活品質的提升,尋找其他替代的藥物 (像是較新的抗憂鬱劑,citalopram與milnacipran) 取代抗精神病劑來處置失智症病人的行為與精神症狀是當務之急。此外,本研究發現臺灣有高達 50% 以上的失智病患接受鎮靜安眠劑處方,但其處方適當性與目前治療指引是不符合的。
英文摘要 Background: There are repeated U.S. Food and Drug Administration(FDA) warnings (2003, 2005, and 2006) on the off-label use of both first and secondary generation antipsychotics for behavioral and psychological symptoms of dementia (BPSD) in geriatric patients worldwide due to increasing mortality rate caused by high incidence of cardiovascular events and aspiration pneumonia. Despite U.S. FDA warnings on the improper use of antipsychotics for the geriatric patients with dementia, the prescription rate of antipsychotics for dementia in Canada is relatively lower comparing with other countries, while the prescription rate of antipsychotics significantly increase from 1.1% in 2000 to 1.8% in 2007. Moreover, the prescription rates of antipsychotics for dementia in U.S. (14.93%-17.7%) and Taiwan (48.8%) are much higher than such prescription rate in Canada. Objectives: The aim of the present study was to determine the prescription rates of psychotropic drugs in geriatric patients with dementia in Taiwan based on the National Health Insurance Research Database (NHIRD, from 2004 to 2006) and the review of medical records at Taipei Medical University (TMU) teaching hospitals. According to the current finding and evidence-base medicine, the present study might provide physicians and pharmacists a new management and care protocol for BPSD to improve patient safety and quality of life. Methods:
The present study was designed as a retrospective study, including the analyses of NHIRD and the review of medical records of TMU-teaching hospitals. First, the present study analyzed 1,449 follow-up patients with dementia who were more than 65 year old from the 1,000,000-people population-wide NHIRD covering 2004 to 2006 to determine the prescription rates of psychotropic drugs in patients with dementia in Taiwan. Second, the present study also reviewed 70 medical records of patients with dementia who were more than 65 year old from the TMU-teaching hospitals (including Wan Fang Medical Center and Shuang Ho Hospital) to investigate the prescription rates of psychotropic drugs from 2005 to 2011. Results: The current results based on a follow-up NHIRD covering 2004 to 2006 indicate that there was no significant change in the high prescription rates of antipsychotics which was up to 40% in patients with dementia (2004 [41.6%]; 2005 [43.0%]; 2006 [40.2%], p > 0.05). Moreover, the prescription rate of sedative/hypnotic drugs (2004 [59.4%]; 2005 [56.2%]; 2006 [50.7%], p < 0.05) was over 50% due to the possible abuse of benzodiazepine derivatives (The prescription rate of benzodiazepine: 49.9%-50.2%). The prescription rate of anticonvulsants (7.6%-8.2%) was not changed during the three-year period. However, the prescription rate of antidepressants (2004 [33.8%]; 2005 [30.6%]; 2006 [27.1%], p < 0.05) was significantly decreased in those follow-up patients with dementia from 2004 to 2006. There were 24%-29% of patients with dementia who received no psychotropic drugs. Moreover, the prescription rates of centrally active drugs in the teaching hospitals were antipsychotics (75.7%), sedative/ hypnotics (58.6%), antidepressants (52.9%), and anticonvulsants (5.7%), respectively. Only 7% of these patients with dementia in teaching hospitals received no psychotropic drugs. Conclusion: This retrospective survey indicates that most Taiwanese clinicians did not follow the FDA warnings on the improper off-label use of antipsychotics for BPSD. Most of Taiwanese physicians prescribed the off-label use of antipsychotics for patients with BPSD in patient population of both the NHIRD and the TMU-teaching hospitals. The prescription rate of antipsychotics in geriatric patients with dementia from the teaching hospitals was two times higher than those patients with dementia from the NHIRD. This may be due to more severe BPSD in the patients with dementia who visited psychiatry/neurology clinics, and the different size of these two databases may be a bias. Antipsychotics should be used only in acute management for agitation, delusions, and hallucinations in patients with dementia, while the long-term use of antipsychotics for PWD is not recommended by the guidelines. Accordingly, physicians and pharmacists should follow the guideline of off-label use of medicine and inform patients and their caregivers that antipsychotics are known to increase the mortality rate in patients with dementia. Eventually, finding an alternative medication such as newer antidepressants (eg. citalopram and milnacipran) for managing BPSD as well as improving patients’ safety and quality of life is imperative. Finally, a possible over prescription and prolong use of sedative/hypnotic drugs in greater than 50% of elderly patients was observed in patients with dementia, which is apparently against the guidelines in the management and use of benzodiazepine derivatives.
論文目次 Chapter I. Introduction....................................1
1.1. Rationales............................................1
1.2. Working Hypotheses....................................2
1.3. Research Goals........................................3
Chapter II. Literature Review..............................4
2.1. Behavioral and Psychological Symptoms of Dementia
(BPSD)................................................4
2.2. Clinical Presentation of BPSD.........................4
2.2.1. Assessment of BPSD..................................4
2.2.2. Clinical Stages of BPSD.............................7
2.3. Etiology and Pathophysiology of BPSD..................9
2.4. Treatment Guidelines and Recommendations for BPSD.....9
2.5. Overview of Pharmacologic Therapy for BPSD...........12
2.5.1. Antipsychotic Drugs: Continuation and
Discontinuation of Treatment for Patients with BPSD12
2.5.2. Antidepressant Drugs...............................17
2.5.3. Other Psychotropic Drugs...........................21
2.6. Clinical Issues......................................21
2.6.1. Early Warnings on Improper Use of Antipsychotics for
Patients with BPSD.................................21
2.6.2. High Mortality Rate in Patients with Dementia due to
Antipsychotic Use..................................22
Chapter III. Methods......................................24
3.1. Data Sources and Study Subjects......................24
3.1.1. Analyses of NHIRD Covering 2004 to 2006............24
3.1.2. Review of Medical Records from TMU-Teaching
Hospitals..........................................26
3.2. Study Endpoints......................................28
3.2.1. Analyses of NHIRD Covering 2004 to 2006............28
3.2.2. Review of Medical Records from TMU-Teaching
Hospitals..........................................28
3.3. Statistical Analyses.................................28
Chapter VI. Results.......................................29
4.1. Demographic Characteristics of Patients with Dementia29
4.1.1. Analyses of NHIRD Covering 2004 to 2006............29
4.1.2. Review of Medical Records from TMU-Teaching
Hospitals..........................................31
4.2. The Primary and Secondary Outcomes...................34
4.2.1. Analyses of NHIRD Covering 2004 to 2006............34
4.2.2. Review of Medical Records from TMU-Teaching
Hospitals..........................................38
Chapter V. Discussion.....................................44
5.1. The Findings of High Prescription Rate of
Antipsychotics for BPSD in Taiwan....................44
5.2. Prescription Rates of Antipsychotics for BPSD in Other
Countries............................................44
5.2.1. General PWD Population.............................44
5.2.2. PWD Living in Long-term Care Institution...........45
5.3. Different Etiology and Treatment between BPSD and
Schizophrenia........................................46
5.3.1. Different Etiology between BPSD and Schizophrenia..46
5.3.2. Slowing down BPSD: A Putative Mechanism of
Neuroprotective Effects by Antidepressants.........46
5.5. Palliative and Symptomatic Management for BPSD.......47
5.6. Ethic Consideration..................................51
5.6.1. Informed Consent: Off-labeled Use of Antipsychotics
for BPSD...........................................51
5.7. Limitations..........................................52
5.7.1. Analyses of NHIRD Covering 2004 to 2006............52
5.7.2. Review of Medical Records from TMU-teaching
hospitals..........................................52
Chapter VI. Conclusions...................................54
References................................................55
Appendix..................................................69
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