進階搜尋


下載電子全文  
系統識別號 U0026-0108201220352000
論文名稱(中文) 臺灣小兒癲癇用藥順從性之研究
論文名稱(英文) Adherence of anti-epileptic drugs in pediatric patients in Taiwan
校院名稱 成功大學
系所名稱(中) 臨床藥學與藥物科技研究所
系所名稱(英) Institute of Clinical Pharmacy and Pharmaceutical sciences
學年度 100
學期 2
出版年 101
研究生(中文) 邵時傑
研究生(英文) Shih-Chieh Shao
學號 S66991029
學位類別 碩士
語文別 中文
論文頁數 124頁
口試委員 指導教授-高雅慧
口試委員-黃朝慶
口試委員-葉鳳英
中文關鍵字 小兒  新診斷癲癇  抗癲癇藥品  用藥順從性 
英文關鍵字 pediatrics  newly diagnosed with epilepsy  anti-epileptic drugs  adherence 
學科別分類
中文摘要 研究背景:病人確診為癲癇後,建議應連續使用抗癲癇藥品達到至少兩年無再發作,才可逐漸停藥。用藥順從性差可能會造成病人癲癇頻繁發作和死亡風險。目前小兒癲癇用藥順從性相關資料並不多,故需加以研究了解其現況,以提供臨床醫師診治參考。
研究目的:調查臺灣新診斷癲癇小兒病人第一年抗癲癇藥品用藥順從性,分析順從性隨時間改變的情況,並評估造成不同順從性的潛在因素。
研究方法:分析2006至2007年臺灣全民健保資料庫,於至少有一次就醫紀錄的小兒中,以每三人隨機抽樣一人的承保對象資料。納入小於18歲、新診斷為癲癇 (ICD-9:345.xx),並接受兩筆以上抗癲癇藥品處方(ATC code: N03A, N05BA09)者。追蹤研究對象一年時間,計算medication possession ratio (MPR)作為抗癲癇藥品用藥順從性之測量,定義MPR<0.8為順從性差,並以多變項羅吉氏迴歸分析造成不同用藥順從性的潛在因素,包含研究對象人口學特徵等。
研究結果:研究納入424位研究對象,其中54.3%為男性,平均年齡為9.9±4.9歲。研究對象第一年平均抗癲癇藥品MPR為0.62,且平均MPR會隨時間逐漸下降。用藥順從性差者共占58.7%,以多變項羅吉氏迴歸分析發現,相對於傳統抗癲癇藥品,起始使用新型抗癲癇藥品治療者會顯著地減少用藥順從性差的風險 (multivariate OR: 0.44, 95% CI: 0.23, 0.83)。
結論:臺灣新診斷癲癇小兒病人第一年平均抗癲癇藥品用藥順從性並不理想。起始抗癲癇藥品的選擇可能為影響用藥順從性的潛在因素。對於順從性不佳所造成的影響與改善策略,則需未來更多研究與思考。
關鍵字: 小兒;新診斷癲癇;抗癲癇藥品;用藥順從性。
英文摘要 Background: Regarding poor adherence may lead to poor seizure control or mortality, patients are diagnosed with epilepsy are suggested to be adherent to anti-epileptic drugs (AEDs) regimen for at least two years. However, the information on AEDs adherence in pediatric patients with epilepsy remained insufficient nowadays.
Purpose: This study aimed to investigate the trend of adherence of AEDs and factors associated with adherence in pediatric patients within one-year period after epilepsy was newly diagnosed.
Methods: We conducted a retrospective cohort study by using claims data which contained one third pediatric patients randomly sampled from Taiwan National Health Insurance Research Database (NHIRD) in the year 2006 and 2007. Patients were aged 18 or less, newly diagnosed with epilepsy (ICD-9: 345.xx), and received more than two AEDs prescriptions (ATC code: N03A, N05BA09). Patients were followed one year from index date to measure the adherence of AEDs using the medication possession ratio (MPR), and non-adherence was defined as MPR less than 0.8. We evaluated factors associated with adherence by using multivariate logistic regression including patient demographics, comorbidities and index drug.
Results: 424 patients were identified with 54.3% of male patients nd the mean age of epilepsy diagnosed was 9.9±4.9 years. MPR was decreased with time. The one-year mean MPR was 0.62, and 58.7% of patients were non-adherent. The factor associarted with adherence was receiving newer AEDs initially. Compared to old AEDs, receiving newer AEDs initially had significantly lower non-adherence risk (multivariate OR: 0.44, 95% CI: 0.23, 0.83).
Conclusion: The first one-year AEDs adherence in pediatrics newly diagnosed with epilepsy was suboptimal, and patients received new AEDs initially had significantly lower non-adherence risk. However, it still needs further studies to investigate the impact of this finding.
論文目次 中文摘要 i
Abstract ii
誌謝 iv
目錄 v
表目錄 ix
圖目錄 xi
附錄 xii
第一篇、新診斷癲癇小兒病人抗癲癇藥品的用藥順從性 1
第一章、研究背景 1
第二章、文獻回顧 3
第一節、小兒癲癇簡介 3
一、定義、病因與分類 3
二、流行病學研究 4
三、治療方式 5
第二節、抗癲癇藥品 5
一、藥理機轉與臨床療效 5
二、副作用 7
三、臨床重要交互作用 9
四、治療指引 10
第三節、小兒癲癇用藥順從性 12
一、順從性的定義 12
二、抗癲癇藥品順從性的測量方式 12
三、抗癲癇藥品用藥順從性情形與影響因素 16
四、抗癲癇藥品用藥順從性的重要性 21
第四節、結論 22
第三章、研究目的及重要性 23
第一節、研究目的 23
第二節、研究重要性 23
第四章、研究方法 24
第一節、研究設計 24
一、研究類型 24
二、研究材料及工具 24
三、研究對象與排除條件 26
四、基本資料與分組 26
五、研究流程 27
第二節、研究名詞、研究變項與操作定義 29
第三節、資料處理流程 35
第四節、統計方法 36
一、統計工具 36
二、統計模式設定 36
三、統計資料分析 36
第五章、研究結果 39
第一節、研究對象納入、排除 39
第二節、研究對象基本資料 41
第三節、抗癲癇藥品用藥順從性 48
一、平均用藥順從性與時間的關係 48
二、一年平均用藥順從性 51
第四節、影響用藥順從性的因素 55
一、單變項羅吉氏回歸 55
二、多變項羅吉氏複回歸 55
第五節、敏感度分析 59
一、敏感度分析一:排除起始使用口服抗癲癇藥品液劑者 59
二、敏感度分析二:排除年平均用藥順從性偏低者 59
第六章、研究討論 61
第一節、研究對象納入與排除情況之分析 61
第二節、研究對象基本資料特性之分析 63
第三節、抗癲癇藥品用藥順從性分析 64
第四節、影響抗癲癇藥品用藥順從性之因素分析 70
第五節、研究限制 72
第七章、結論與建議 74
第八章、未來研究方向 75
第二篇、臨床藥事服務: 小兒癲癇門診藥事服務暨用藥順從性探討 76
第一章、服務背景 76
第二章、服務目的與進行方法 77
第一節、服務目的 77
第二節、服務進行方法 77
一、照會方式與進行流程 77
二、服務時間 78
三、問卷與資料來源 82
四、衛教工具與資料來源 86
第三章、服務結果 87
第一節、研究對象基本資料 87
第二節、研究對象抗癲癇藥品之疑慮 89
第三節、研究對象抗癲癇藥品之知識 91
第四節、研究對象抗癲癇藥品之用藥順從性探討 93
一、MMAS-8-item問卷結果 93
二、MPR結果 95
第五節、抗癲癇藥品用藥順從性一致性結果 97
第六節、討論 98
第四章、感想與心得 101
參考資料 102
附錄一、小兒癲癇病人用藥指導單張 108
附錄二、抗癲癇藥品指導單張 109
參考文獻 1. French JA, Pedley TA, Initial management of epilepsy. N Engl J Med, 2008. 359: p. 166-76.
2. Chen CC, Chen LS, Yen MF, Chen HH, Liou HH, Geographic variation in the age- and gender-specific prevalence and incidence of epilepsy: Analysis of Taiwanese National Health Insurance-based data. Epilepsia, 2012. 53(2): p. 283-290.
3. Hay W, Levin M, Deterding R, Sondheimer J (2010), Current diagnosis & treatment: pediatrics (20th ed), New York : McGraw-Hill Medical.
4. Raspall-Chaure M, Neville BG, Scott RC, The medical management of the epilepsies in children: conceptual and practical considerations. Lancet Neurol, 2008. 7(1): p. 57-69.
5. Garnett WR, Antiepileptic drug treatment: outcomes and adherence. Pharmacotherapy, 2000. 20(8 Pt 2): p. 191S-199S.
6. Koumoutsos JE, Poor AED compliance may lead to seizures and dosage increases in children with epilepsy. Neurology Reviews, 2008. 16(2):p. 13.
7. Chang YH, Li CY, Tung TH, Tsai JJ, Lu TH., Age-period-cohort analysis of mortality from epilepsy in Taiwan, 1971-2005. Seizure, 2011. 20(3): p. 240-3.
8. Modi AC, Rausch JR, Glauser TA, Patterns of nonadherence to antiepileptic drug therapy in children with newly diagnosed epilepsy. JAMA, 2011. 305(16): p. 1669-1676.
9. Modi AC, Morita DA, Glauser TA, One-month adherence in children with new-onset epilepsy: white-coat compliance does not occur. Pediatrics, 2008. 121(4): p. e961-6.
10. Modi AC, Ingerski LM, Rausch JR, Glauser TA, Drotar D, White coat adherence over the first year of therapy in pediatric epilepsy. J Pediatr, 2012.
11. Campbell JP, Maxey VA, Watson WA, Watson, Hawthorne effect: implications for prehospital research. Ann Emerg Med, 1995. 26(5): p. 590-4.
12. Shorvon SD, The causes of epilepsy: changing concepts of etiology of epilepsy over the past 150 years. Epilepsia, 2011. 52(6): p. 1033-44.
13. Shorvon SD, The etiologic classification of epilepsy. Epilepsia, 2011. 52(6): p. 1052-7.
14. Kasper DL, Braunwald E, Longo D, Longo DL, Hauser S, Fauci AS, Jameson JL (2004), Harrison's principles of internal medicine (16th ed), New York : McGraw-Hill Medical.
15. Berg AT, et al., Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE commission on classification and terminology, 2005-2009. Epilepsia, 2010. 51(4): p. 676-85.
16. Guerrini R, Epilepsy in children. Lancet, 2006. 367(9509): p. 499-524.
17. Mac TL, Tran DS, Quet F, Odermatt P, Preux PM, Tan CT, Epidemiology, aetiology, and clinical management of epilepsy in Asia: a systematic review. Lancet Neurol, 2007. 6(6): p. 533-543.
18. Pellock JM, Dodson WE, Bourgeois BFD. (2007), Pediatric Epilepsy: Diagnosis and Therapy (3rd ed.), New York : Demos Medical Pub.
19. 姜采玲 (2008),「以台灣全民健保資料庫分析門診新癲癇個案診斷率與藥物處方趨勢」,臺北醫學大學藥學研究所碩士論文。
20. Miller V, Palermo TM, Grewe SD, Quality of life in pediatric epilepsy: demographic and disease-related predictors and comparison with healthy controls. Epilepsy & Behavior, 2003. 4(1): p. 36-42.
21. Shorvon, SD (2010), Handbook of Epilepsy Treatment (3rd ed), Chichester, West Sussex, UK : Wiley-Blackwell.
22. Absoud M, McShane T, When should epilepsy be treated? Paediatrics and Child Health., 2009. 19(5): p. 216-224.
23. Dipiro J, Talbert RL (2011), Pharmacotherapy: a pathophysiologic approach (8th ed.), New York : McGraw-Hill Medical.
24. Connock M, et al., The clinical effectiveness and cost-effectiveness of newer drugs for children with epilepsy. A systematic review. Health Technol Assess, 2006. 10(7): p. iii, ix-118.
25. Kwan P, Brodie MJ, Combination therapy in epilepsy: when and what to use. Drugs, 2006. 66(14): p. 1817-29.
26. Zaccara G, Franciotta D, Perucca E, Idiosyncratic adverse reactions to antiepileptic drugs. Epilepsia, 2007. 48(7): p. 1223-44.
27. Perucca E, Meador KJ, Adverse effects of antiepileptic drugs. Acta Neurol Scand Suppl, 2005. 181: p. 30-5.
28. Eatock J, Baker GA, Managing patient adherence and quality of life in epilepsy. Neuropsychiatr Dis Treat, 2007. 3(1): p. 117-31.
29. Patsalos PN, et al., The importance of drug interactions in epilepsy therapy. Epilepsia, 2002. 43(4): p. 365-85.
30. Johannessen SI, Landmark CJ, Antiepileptic drug interactions - principles and clinical implications. Curr Neuropharmacol, 2010. 8(3): p. 254-67.
31. Patsalos PN, Perucca E, Clinically important drug interactions in epilepsy: interactions between antiepileptic drugs and other drugs. Lancet Neurol, 2003. 2(8): p. 473-481.
32. Glauser T, et al., ILAE treatment guidelines: evidence-based analysis of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia, 2006. 47(7): p. 1094-120.
33. National Institute of Health and Clinical Excellence. The epilepsies: the diagnosis and management of the epilepsies in adults and children in primary and secondary care. (Cited on May 23, 2012. Available form: http://publications.nice.org.uk/the-epilepsies-the-diagnosis-and-management-of-the-epilepsies-in-adults-and-children-in-primary-and-cg137).
34. 全民健康保險藥品給付規定:續言與第一章神經系統藥物 (Cited on May 13, 2012. Available form: http://www.nhi.gov.tw/02hospital/hospital_file/chap1.doc).
35. Paschal AM, et al., Measures of adherence to epilepsy treatment: review of present practices and recommendations for future directions. Epilepsia, 2008. 49(7): p. 1115-1122.
36. Rapoff, M.A. (2010), Adherence to pediatric medical regimens (2nd ed.), Boston, MA : Springer-Verlag US.
37. 詹季臻 (2010),「國人服藥順從性與醫療人員互動影響因素之探討」,國立成功大學臨床藥學研究所碩士論文。
38. Osterberg L, Blaschke T, Adherence to Medication. N Engl J Med, 2005. 353: p. 487-97.
39. Peterson AM, et al., A checklist for medication compliance and persistence studies. Value Health, 2007. 10 (1): p. 3-12.
40. Friedman IM, et al., Compliance with anticonvulsant therapy by epileptic youth. Relationships to psychosocial aspects of adolescent development. J Adolesc Health Care, 1986. 7(1): p. 12-7.
41. Hazzard A, Hutchinson SJ, Krawiecki N, Factors related to adherence to medication regimens in pediatric seizure patients. J Pediatr Psychol, 1990. 15(4): p. 543-55.
42. Mitchell WG, Scheier LM, Baker SA, Adherence to treatment in children with epilepsy: who follows "doctor's orders"? Epilepsia, 2000. 41(12): p. 1616-25.
43. Asadi-Pooya AA, Drug compliance of children and adolescents with epilepsy. Seizure, 2005. 14(6):393-5.
44. 葉錦瑩、陳怡樺、王豊裕編譯 (2009),「流行病學」,臺北市:臺灣愛思唯爾,p.199。
45. Perucca P, Hesdorffer DC, Gilliam FG, Response to first antiepileptic drug trial predicts health outcome in epilepsy. Epilepsia, 2011. 52(12): p. 2209-15.
46. Wirrell E, et al., Prognostic significance of failure of the initial antiepileptic drug in children with absence epilepsy. Epilepsia, 2001. 42(6): p. 760-3.
47. Al-Aqeel S, Al-Sabhan J, Strategies for improving adherence to antiepileptic drug treatment in patients with epilepsy Cochrane Database Syst Rev, 2011(1): p. CD008312.
48. Faught RE, et al., Impact of nonadherence to antiepileptic drugs on health care utilization and costs: Findings from the RANSOM study. Epilepsia, 2009. 50(3): p. 501-509.
49. 國家衛生研究院全民健康保險資料庫:各檔案間串檔變項說明 (Cited on May 13, 2012. Available form: http://www.nhri.org.tw/nhird/file_date/connect2.gif).
50. 高雅慧、鄭靜蘭 (2011),健保給付藥品品項的藥品藥理治療分類代碼之建立,100年度委託科技研究計畫期末報告。
51. 中央健康保險局 / 醫事機構 / 2001年ICD-9-CM疾病碼一覽表 (Cited on May 13, 2012. Available form: http://www.nhi.gov.tw/Resource/webdata/Attach_3469_2_ICD2001-更新版.pdf).
52. 行政院衛生署中央健康保險局業務執行報告: 100年度11月份 (Cited on May 13, 2012. Available form: http://www.nhi.gov.tw/Resource/webdata/20756_2_199執行報告11月(送印版).pdf).
53. Guidelines for ATC classification and DDD assignment, 2011. (Cited on May 23, 2012. Available form: http://www.whocc.no/filearchive/publications/2011guidelines.pdf).
54. 林為森等譯 (2008),「生物統計原理」,臺北市:新加坡商聖智學習出版,p.163。
55. 全民健康保險研究資料庫之服務簡介 (Cited on May 13, 2012. Available from: http://nhird.nhri.org.tw/brief_01.htm).
56. Manjunath R, et al., Association of antiepileptic drug nonadherence with risk of seizures in adults with epilepsy. Epilepsy Behav, 2009. 14(2): p. 372-8.
57. Ettinger AB, et al., Prevalence and cost of nonadherence to antiepileptic drugs in elderly patients with epilepsy. Epilepsy Behav, 2009. 14(2): p. 324-9.
58. Davis KL, Candrilli SD, Edin HM, Prevalence and cost of nonadherence with antiepileptic drugs in an adult managed care population. Epilepsia, 2008. 49(3): p. 446-54.
59. Berg AT, et al., Newly diagnosed epilepsy in children: presentation at diagnosis. Epilepsia, 1999. 40(4): p. 445-52.
60. Beilmann A, et al., Incidence of childhood epilepsy in Estonia. Brain Dev, 1999. 21(3): p. 166-74.
61. Pellock JM, Understanding co-morbidities affecting children with epilepsy. Neurology, 2004. 62(5 Suppl 2): p. S17-23.
62. Noeker M, Haverkamp-Krois A, Haverkamp F, Development of mental health dysfunction in childhood epilepsy. Brain and Development, 2005. 27(1): p. 5-16.
63. Wong V, Study of seizure and epilepsy in Chinese children in Hong Kong: period prevalence and patterns. J Child Neurol, 2004. 19(1): p. 19-25.
64. Steiner JF, et al., A general method of compliance assessment using centralized pharmacy records. Description and validation. Med Care, 1988. 26(8): p. 814-23.
65. Hansen RA, et al., Comparison of methods to assess medication adherence and classify nonadherence. Ann Pharmacother, 2009. 43(3): p. 413-22.
66. World Health Organization. Adherence to Long-Term Therapy: Evidence for Action, 2003. (Cited on Jul 13, 2012. Available from: http://apps.who.int/medicinedocs/pdf/s4883e/s4883e.pdf).
67. Sanz EJ, Concordance and children's use of medicines. BMJ, 2003. 327(7419): p. 858-60.
68. Baker GA, et al., Quality of life of people with epilepsy: a European study. Epilepsia, 1997. 38(3): p. 353-62.
69. Kuan YC, et al., Treatment-seeking behavior of people with epilepsy in Taiwan: a preliminary study. Epilepsy Behav, 2011. 22(2): p. 308-12.
70. Camfield PR, et al., If a first antiepileptic drug fails to control a child's epilepsy, what are the chances of success with the next drug? J Pediatr, 1997. 131(6): p. 821-4.
71. Ma MS, et al., Effectiveness of the first antiepileptic drug in the treatment of pediatric epilepsy. Pediatr Neurol, 2009. 41(1): p. 22-6.
72. St Louis EK, Truly "rational" polytherapy: maximizing efficacy and minimizing drug interactions, drug load, and adverse effects. Curr Neuropharmacol, 2009. 7(2): p. 96-105.
73. Bautista RE, Rundle-Gonzalez V, Effects of antiepileptic drug characteristics on medication adherence. Epilepsy Behav, 2012. 23(4): p. 437-41.
74. Cheng SH, Chiang TL, The effect of universal health insurance on health care utilization in Taiwan. Results from a natural experiment. JAMA, 1997. 278(2): p. 89-93.
75. 顧漢凌 (2006),「全民健保體系下醫療資源分佈對個人醫療使用的影響」,國立東華大學國際經濟研究所碩士論文。
76. Koch MW, Polman SK, Oxcarbazepine versus carbamazepine monotherapy for partial onset seizures. Cochrane Database Syst Rev, 2009(4): p. CD006453.
77. Muller M, Marson AG, Williamson PR, Oxcarbazepine versus phenytoin monotherapy for epilepsy. Cochrane Database Syst Rev, 2006(2): p. CD003615.
78. Shorvon S, Oxcarbazepine: a review. Seizure, 2000. 9(2): p. 75-9.
79. Ettinger AB, Baker GA, Best clinical and research practice in epilepsy of older people: focus on antiepileptic drug adherence. Epilepsy Behav, 2009. 15 Suppl 1: p. S60-3.
80. 行政院衛生署中央健保局網站:健保用藥品項查詢 (Cited on May 13, 2012. Available form: http://www.nhi.gov.tw/).
81. 任佩蓉 (2011),「癲癇病患抗癲癇藥物替換之探討」,嘉南藥理科技大學醫療資訊管理研究所碩士論文。
82. Dawood OT, et al., Medication compliance among children. World J Pediatr, 2010. 6(3): p. 200-2.
83. 醫院以病人為中心門診整合照護試辦計畫 (Cited on May 13, 2012. Available form: http://www.nhi.gov.tw/Resource/webdata/19419_2_1000004644A-%E5%85%AC%E5%91%8A%E9%99%84%E4%BB%B6-100%E5%B9%B4%E9%86%AB%E9%99%A2%E4%BB%A5%E7%97%85%E4%BA%BA%E7%82%BA%E5%BF%83%E6%95%B4%E5%90%88%E7%85%A7%E8%AD%B7%E8%A8%88%E7%95%AB.pdf).
84. Sweileh WM, et al., Self-reported medication adherence and treatment satisfaction in patients with epilepsy. Epilepsy Behav, 2011. 21(3):301-5.
85. Liu L, Yiu CH, Yen DJ, Chou MH, Lin MF, Medication education for patients with epilepsy in Taiwan. Seizure, 2003. 12(7):473-7.
86. Munoz SR, Bangdiwala SI, Interpretation of Kappa and B statistics measures of agreement. Journal of Applied Statistics, 1997. 24(1): p. 105-112.
87. Carpay JA, Aldenkamp AP, van Donselaar CA, Complaints associated with the use of antiepileptic drugs: results from a community-based study. Seizure, 2005. 14(3): p. 198-206.
88. Guenette L, et al., Measures of adherence based on self-report exhibited poor agreement with those based on pharmacy records. J Clin Epidemiol, 2005. 58(9): p. 924-33.
89. Morris AB, et al., Factors associated with drug adherence and blood pressure control in patients with hypertension. Pharmacotherapy, 2006. 26(4): p. 483-92.
90. Koshy S, Role of pharmacists in the management of patients with epilepsy. Int J Pharm Pract, 2012. 20(1): p. 65-8.
論文全文使用權限
  • 同意授權校內瀏覽/列印電子全文服務,於2017-08-20起公開。
  • 同意授權校外瀏覽/列印電子全文服務,於2017-08-20起公開。


  • 如您有疑問,請聯絡圖書館
    聯絡電話:(06)2757575#65773
    聯絡E-mail:etds@email.ncku.edu.tw