臺灣博碩士論文加值系統

研究背景：抗精神病藥物治療是精神分裂症成功治療的一個重要因素，然而，在藥物持續治療過程中大約有40%到60%的精神分裂症患者，因不遵從藥物治療，而成為主要的問題，所以，不遵從藥物治療對於精神分裂症的成功治療是一個很重要的障礙，而且導致臨床及醫療支出成本上沉重的負擔，因此本研究之目的在探討及預測精神分裂症病患藥物遵從性的影響因素及特徵。
方法：研究設計為相關性研究，採立意取樣，以台灣南部一所醫學中心及一所區域教學醫院之精神分裂症病患為對象，資料收集於2007年7月至2008年2月，分析共90位依據DSM-IV診斷為精神分裂症患者，利用結構式問卷量表，進行橫斷性訪談，測量結果包括藥物治療態度、藥物遵從性、藥物副作用、病識感及社會支持度等，將所得資料經由SPSS Windows 12.0中文版之統計軟體，運用描述性統計、t-test、單因子變異數分析、Kruskal-Wallis 檢定、皮爾森積差相關和逐步迴歸分析等方法進行統計分析。
結果：研究結果顯示年齡、教育程度和抗精神病藥物種類對藥物遵從性有顯著性差異 (p<0.05)，年輕者、教育程度較低者及使用第二代抗精神病藥物者其藥物遵從性較差。在變項與藥物遵從性之相關性分析中，結果顯示對於藥物的正向(r=0.39, p<0.001)及負向態度(r=－0.32, p=0.002)、整體藥物副作用(r=－0.42, p<0.001)及病識感(r=0.28, p=0.009)具有顯著相關性，但是社會支持度顯示與藥物遵從性之間並無相關性。在逐步迴歸的分析中，顯示抗膽鹼激素藥物副作用(p=0.002)、藥物正向態度(p=0.011)與病識感中接受治療的情況(p=0.013)，三者為影響精神分裂症病患藥物遵從性的重要預測因子。
結論：探討精神分裂症病患藥物遵從性預測因子，可以提供最佳的遵從性介入治療之參考，研究資料可以提供臨床人員未來在改善精神分裂症病患藥物遵從性介入治療的方向，並且在這個領域中進一步設計出提高患者藥物遵從性的治療策略。

Background: Antipsychotic medication is a critical component of successful treatment for schizophrenia. However, nonadherence to these medications continues to be a major problem for 40% to 60% of patients with schizophrenia. Antipsychotic nonadherence is an important barrier to the successful treatment of schizophrenia and can lead to clinical and economic burdens for health services. The aim of this study was to identify the features of schizophrenia that predict antipsychotic medication adherence.
Method: A correlation research design and purposive sampling were used in the study. Schizophrenia patients in a medical center and a regional teaching hospital in the south part of Taiwan were chose. The data was collected from July 2007 to February 2008. Analyses included 90 patients with DSM-IV diagnoses of schizophrenia, using structural questionnaire and cross section interview. Outcome measures included attitudes toward treatment, self-reported medication adherence, drug adverse effects, insight and social support. Statistical analyses were performed with descriptive statistics, t-test, one-way ANOVA, Kruskal-Wallis test, Pearson’s correlation coefficient and stepwise regression by SPSS for Windows 12.0.
Results: The results indicated significant difference in the proportion of patients with age, education level and prescribed antipsychotic medication (p＜0.01). Younger patients, lower education level and second-generation antipsychotic had showed poor medication adherence. Correlation analysis was carried out to examine associations of variables with adherence to medication. Positive attitudes toward medication (r=0.39, p<0.001) and negative attitudes toward medication (r=－0.32, p=0.002) were correlated significantly with medication adherence. In addition, there were significant correlation between adherence and antipyschotic side effects (r=－0.42, p<0.001) and total insight (r=0.28, p=0.009). However, Social support showed no significant correlation with adherence. In a stepwise regression analysis, adverse effects of anticholinergic (p=0.002), positive attitude toward medication (p=0.011) and insight of need for treatment (p=0.013) were major predictors of medication adherence in patient of schizophrenia.
Conclusion：It may be possible to identify patients most likely to benefit from adherence intervention. The data presented here will help to inform future research of clinical interventions to improve medication adherence in schizophrenia and help to design further work and treatment strategies for medication adherence enhancement in this area.

中文摘要 ………………………………………………………………I
英文摘要 ……………………………………………………………III
致謝 ……………………………………………………………………V
目次……………………………………………………………………VI
表目錄…………………………………………………………………XI
圖目錄………………………………………………………………XIII
第一章 緒論……………………………………………………………1
　　第一節 研究背景…………………………………………………1
　　第二節 研究目的…………………………………………………3
第三節 研究問題…………………………………………………3
第二章 文獻探討………………………………………………………4
　　第一節 精神分裂症之相關研究…………………………………4
　　　　一、精神分裂症 ……………………………………………4
　　　　二、精神分裂症之流行病學 ………………………………5
　　　　三、精神分裂症之診斷 ……………………………………6
　　　　四、精神分裂症之臨床表徵 ………………………………9
　　　　五、精神分裂症之病因學 …………………………………9
　　　　六、精神分裂症之病程與預後 ……………………………13
　　第二節 抗精神病藥物之相關研究………………………………14
　　　　一、抗精神病藥物之發展史 ………………………………14
　　　　二、抗精神病藥物之種類 …………………………………17
　　　　三、抗精神病藥物之藥理作用 ……………………………22
　　　　四、抗精神病藥物之動力學及藥效學特性 ………………25
　　　　五、抗精神病藥物之副作用 ………………………………33
　　第三節 藥物遵從性之相關研究…………………………………36
　　　　一、藥物遵從性之定義與概念 ……………………………36
　　　　二、藥物遵從性之測量與方法 ……………………………37
　　　　三、藥物遵從性之相關影響因素 …………………………39
　　　　　　(一)社會人口學對藥物遵從性的影響 ………………39
　　　　　　(二)疾病特性對藥物遵從性的影響 …………………44
　　　　　　(三)藥物治療對藥物遵從性的影響 …………………44
　　　　　　(四)病識感對藥物遵從性的影響 ……………………45
　　　　　　(五)社會支持度對藥物遵從性的影響 ………………46
第三章 研究架構………………………………………………………48
第四章 研究方法………………………………………………………49
　　第一節 研究設計…………………………………………………49
　　第二節 研究對象…………………………………………………49
　　第三節 研究工具及信效度………………………………………50
　　第四節 研究步驟…………………………………………………56
　　第五節 研究變項之定義…………………………………………57
　　第六節 資料分析方法……………………………………………58
　　第七節 倫理考量…………………………………………………60
第五章 研究結果………………………………………………………61
　　第一節 研究對象基本屬性之描述………………………………61
　　第二節 精神分裂症病患藥物態度、藥物遵從性、藥物副作用
　　　　　 、病識感、社會支持度之評量結果……………………66
　　　　一、精神分裂症病患藥物態度之評量結果 ………………66
　　　　二、精神分裂症病患藥物遵從性之評量結果 ……………67
　　　　三、精神分裂症病患藥物副作用之評量結果 ……………69
　　　　四、精神分裂症病患社會支持度之評量結果 ……………71
　　　　五、精神分裂症病患病識感之評量結果 …………………73
　　第三節 精神分裂症病患基本屬性、藥物種類、藥物態度、藥物
副作用、病識感、社會支持度與藥物遵從性之相關性…75
　　　　一、精神分裂症病患基本屬性、疾病因素與藥物遵從性
　　　　　　之相關性 ………………………………………………75
　　　　二、精神分裂症病患藥物種類與藥物遵從性之相關性 …78
　　　　三、精神分裂症病患藥物態度與藥物遵從性之相關性 …78
　　　　四、精神分裂症病患藥物副作用與藥物遵從性之相關性 80
　　　　五、精神分裂症病患病識感與藥物遵從性之相關性 ……81
　　　　六、精神分裂症病患社會支持度與藥物遵從性之相關性 81　　第四節 精神分裂症病患藥物遵從性之重要預測因子…………82
第六章 討論……………………………………………………………85
　　第一節 精神分裂症病患之個人基本屬性、疾病因素與藥物
遵從性之關係 ……………………………………………………85
　　第二節 精神分裂症病患之藥物態度與藥物遵從性之關係……87
　　第三節 精神分裂症病患之藥物種類、藥物副作用與藥物遵
從性之關係 ………………………………………………………88
　　第四節 精神分裂症病患之社會支持度與藥物遵從性之關係…90
　　第五節 精神分裂症病患之病識感與藥物遵從性之關係………91
　　第六節 精神分裂症病患藥物遵從性之預測因子………………92
　　第七節 研究限制…………………………………………………94
第七章 建議與結論……………………………………………………96
第一節 建議………………………………………………………96
第二節 結論………………………………………………………97
參考文獻 ………………………………………………………………99
附錄一 受訪者同意書 ………………………………………………108
附錄二 研究問卷 ……………………………………………………109
附錄三 人體試驗委員會研究計畫同意書 …………………………115

1.Patel MX, David AS. Medication adherence: predictive factors and enhancement strategies. Psychiatry 2007; 6(9): 357-361.
2.Fenton WS, Blyler CR, Heinssen RK. Determinants of medication compliance in schizophrenia: empirical and clinical findings. Schizophr. Bull. 1997; 23: 637-651.
3.Lacro JP, Dunn LB, Dolder CR, Leckband SG, Jeste DV. Prevalence of and risk factors for medication nonadherence in patients with schizophrenia: a comprehensive review of recent literature. J. Clin. Psychiatry 2002; 63: 892-909.
4.Valenstein M, Blow FC, Copeland LA, McCarthy JF, Zeber JE, Gillon L, Bingham R. Poor antipsychotic adherence among patients with schizophrenia: medication and patient factors. Schizophr. Bull. 2004; 30(2): 255-264.
5.Knapp M, King D, Pugner K, Lapuerta P. Non-adherence to antipsychotic medication regimens: associations with resource use and costs. Br. J. Psychiatry 2004; 184: 509-516.
6.Gilmer TP, Dolder CR, Lacro JP, Folsom DP, Lindamer L, Garcia P, Jeste DV. Adherence to treatment with antipsychotic medication and health care costs among medical beneficiaries with schizophrenia. Am. J. Psychiatry 2004; 161(4): 692-699.
7.Sun SX, Liu GG, Christensen DB, Fu AZ. Review and analysis of hospitalization costs associated with antipsychotic nonadherence in the treatment of schizophrenia in the United States. Curr. Med. Res. Opin. 2006; 23(10): 2305-2312.
8.Donohoe G. Adherence to antipsychotic treatment in schizophrenia. Dis. Manage. Health Outcomes 2006; 14(4): 207-214.
9.Lieberman JA, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, Keefe RSE, Davis SM, Davis CE, Lebpwitz BD, Severe J, Hasiao JK, the CATIE Investigators. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N. Engl. J. Med. 2005; 353(12): 1209-1223.
10.Stroup TS, Lieberman JA, McEvoy JP, Swartz MS, Davis SM, Rosenheck RA, Perkins DO, Keefe RSE, Davis CE, Severe J, Hsiao JK, the CATIE Investigators. Effectiveness of olanzapine, quetiapine, risperidone, and ziprasidone in patients with chronic schizophrenia following discontinuation of a previous atypical antipsychotic. Am. J. Psychiatry 2006; 163(4): 611-622.
11.McEvoy JP, Lieberman JA, Perkins DO, Hamer RM, Gu H, Lazarus A, Sweitzer D, Weiden COP, Strakowski SD. Efficacy and tolerability of olanzapine, quetiapine, and risperidone in the treatment of early psychosis: a randomized, double-blind 52-week comparison. Am. J. Psychiatry 2007; 164(7): 1050-1060.
12.Lieberman JA, Perkins D, Belger A, Chakos M, Jarskog F, Boteva K, Gilmore J. The early stages of schizophrenia: speculations on pathogenesis, pathophysiology, and therapeutic approaches. Biol. Psychiatry 2001; 50(11): 884–897.
13.Emsley R, Rabinowitz J, Medori R. Time course for antipsychotic treatment response in first episode schizophrenia. Am. J. Psychiatry 2006; 163(4): 743-745.
14.Robinson D, Woerner MG, Alvir JMJ, Bilder R, Goldman R, Geisler S, Koreen A, Sheitman B, Chakos M, Mayerhoff D, Lieberman JA. Predictors of relapse following response from a first episode of schizophrenia or schizoaffective disorder. Arch. Gen. Psychiatry 1999; 56(3): 241-247.
15.李明濱．實用精神醫學．國立台灣大學醫學院，1999，227-245。
16.Waener R, Girolamo G. Epidemiology of mental discorders and psychosocial problems: Schizophrenia. World Health Organization, Geneva. 1995.
17.Mueser KL, Mc Gurk SR. Schizophrenia. Lancet 2004; 363(9426): 2063-2072.
18.Kaplan HI, Sadock BJ. Synopsis of Psychiatry, 9th ed. Williams &Wilkins, New York. 2003.
19.Lin TY. A study of incidence of mental disorders in Chinese and other cultures. Psychiatry 1953; 16: 315-335.
20.Lin TY, Rin H, Yeh EK, Chen CC. Mental disorders in Taiwan fifteen year later: a preliminary report. Mental Health Research in Asia and the Pacific. East-Wet Center Press, Honolulu. 1969.
21.Hwu HG, Yeh EK, Chang LY. Prevalence of psychiatric disorders in Taiwan defined by the Chinese Diagnostic Interview Schedule. Acta Psychiatry Scand. 1989; 19: 136-147.
22.Chien IC, Chou YJ, Lin CH, Bih SH, Chou P, Chang HJ. Prevalence and incidence of schizophrenia among national health insurance enrollees in Taiwan, 1996-2001. Psychiatry Clin. Neurosci. 2004; 58: 611-618.
23.胡海國．精神分裂症之社區流行病學．當代醫學，2002，29 (9），717-727。
24.王俊凱、周元華．精神分裂症．臨床醫學，2005，55，455-425。
25.孔繁鐘．DSM-IV 精神疾病的診斷與統計．合紀圖書出版社，2000。
26.楊立光、李文貴．抗精神病藥物之發展沿革及最新趨勢．臨床醫學，2007，59，231-237。
27.Davis KL, Kahn RS, Ko G, Davidson M. Dopamine in schizophrenia: a review and reconceptualization. Am. J. Psychiatry 1991; 148(11): 1474-1486.
28.Harrison PJ. The neuropathology of schizophrenia: a critical review of the data and their interpretation. Brain 1999; 122: 593-624.
29.張明峰．非典型抗精神病藥物之臨床探討．藥學雜誌，2003，77(2)，106-113。
30.Shen WW. A history of antipsychotic drug development. Compr. Psychiatry 1999; 11: 145–158.
31.周元華、蘇東平．抗精神病藥物之最近發展．臨床醫學，2005， 55，247-252。
32.沈武典．21世紀臨床精神藥物學．合紀圖書出版社，2004。
33.Horacek J, Valesova VB, Kopecek M, Palenicek T, Dockery C, Mohr P, Hoschl C. Mechanism of action of atypical antipsychotic drug and the neurobiology of schizophrenia. CNS Drugs 2006; 20(5): 389-409.
34.Markowitz JS, Brown CS, Moore TR. Atypical antipsychotics parI: pharmacology, pharmacokinetics, and efficacy. Ann. Pharmacother. 1999; 33(1): 73-85.
35.Brown C, Markowitz J, Moore TR, Parker NG. Atypical antipsychotics part II: adverse effects, drug interaction and costs. Ann. Pharmacother. 1999; 33(2): 210-217.
36.Koda-Kimble MA, Young LY, Kradjan WA, Guglielmo BJ, Allredge BK, Corelli RL. Applied Therapeutics: the clinical use of drugs. Eighth Edition. 1217-1288.
37.Spina E, Leon JD. Metabolic drug interactions with newer antipsychotics: a comparative review. Basic Clin. Pharmaco. Toxicol. 2007; 100(1): 4-22.
38.Mauri MC, Volonteri LS, Colasanti A, Fiorentini A, Gaspari IF, Bareggi SR. Clinical pharmacokinetics of atypical antipsychotics. Clin. Pharmacokinet. 2007; 46(5): 359-388.
39.Kinon BJ, Ahl J, Stauffer VL, Hill AL, Buckley PF. Dose response and atypical antipsychotics in schizophrenia. CNS Drugs 2004; 18(9): 597-616.
40.Chang WH. Selection of antipsychotics for treatment of schizophrenia. Taiwanese H. Psychiatry 2005; 19: 264-282.
41.Sprague DA, Loewen PS, Raymond CB. Selection of antipsychotics for the management of schizophrenia. Ann. Pharmacother. 2004; 38: 313-319.
42.Dolder CR, Lacro JP, Leckband S, Jeste DV. Intervention to improve antipsychotic medication adherence: review of recent literature. J. Clin. Psychophar. 2003; 23(4): 389-399.
43.Haynes RB, Taylor DW, Sackett DL, editors. Determinants of compliance: the disease and the mechanics in treatment. In: Compliance in health care. Baltimore (MD): Johns Hopkins University Press. 1979; 3-18.
44.Hughes CM. Medication non-adherence in the elderly. Drugs Aging 2004; 21(12): 793-811.
45.Velligan DI, Francis Lam YM, Glahn DC, Barrett JA, Maples NJ, Ereshefsky L, Miller AL. Defining and assessing adherence to oral antipsychotics: A review of the literature. Schizophr. Bull. 2006; 32(4): 724-742.
46.Farmer KC. Methods for measuring and monitoring medication regimen adherence in clinical trials and clinical practice. Clin. Therapeutics 1999; 21(6): 1074-1090.
47.Ascher-Svanum H, Zhu B, Faries D, Lacro JP, Dolder CR. A prospective study of risk factors for nonadherence with antipsychotic medication in the treatment of schizophrenia. J. Clin. Psychiatry 2006; 67: 1114-1123.
48.Day JC, Bentall RP, Roberts C, Randall F, Rogers A, Cattell D, Healy D, Rae P, Power C. Attitudes toward antipsychotic medication. Arch. Gen. Psychiatry 2005; 62: 711-724.
49.Dolder CR, Lacro JP, Dunn LB, Jeste DV. Antipsychotic medication adherence: is there a difference between typical and atypical agents? Am. J. Psychiatry 2002; 159(11): 103-108.
50.Freudenreich O, Cather C, Evins AE, Henderson DC, Goff DC. Attitudes of schizophrenia outpatients toward psychiatric medications: relationship to clinical variables and insight. J. Clin. Psychiatry 2004; 65: 1372-1367.
51.Hudson TJ, Owen RR, Thrush CR, Han X, Pyne JM, Thapa P, Sullivan G. A pilot study of barriers to medication adherence in schizophrenia. J. Clin. Psychiatry 2004; 65: 211-216.
52.Hui CLM, Chen EYH, Kan CS, Yip KC, Law CW, Chiu CPY. Detection of non-adherent behaviour in early psychosis. Aus. N. Z. J. Psychiatry 2006; 40(5): 446-451.
53.Janssen B, Gaebel W, Martin H, Komaharadi F, Lindel B, Weinmann S. Evaluation of factors influencing medication compliance in inpatient treatment of psychotic disorders. Psychopharmacol. 2006; 187: 229-236.
54.Kamali M, Kelly BD, Clarke M, Browne S, Gervin M, Kinsella A, Lane A, Larkin C, O’callaghan E. A prospective evaluation of adherence to medication in first episode schizophrenia. Eur. Psychiatry 2006; 21: 29-33.
55.Lan CM, Shiau SJ, Lin LC. Knowledge, beliefs, attitude, and drug compliance in schizophrenic patients. Tzu. Chi. Med. J. 2003; 15: 369-375.
56.Mutsatsa SH, Joyce EM, Hutton SB, Webb E, Gibbins H, Paul S, Barnes TRE. Clinical correlated of early medication adherence: West London first episode schizophrenia study. Acta Psychiatry Scand. 2003; 108: 439-446.
57.Perkins DO, Johnson JL, Hamer RM, Zipirsky RB, Keefe RS, Centorrhino F, Green AI, et al. Predictors of antipsychotic medication adherence in patients recovering from a first psychotic episode. Schizophr. Res. 2006; 83: 53-63.
58.Vauth R, Loschmann C, Rusch N, Corrigan PW. Understanding adherence to neuroleptic treatment in schizophrenia. Psychiatry Res. 2004; 126: 43-49.
59.Yamada K, Watanabe K, Nemoto N, Hidechika F, Chikaraishi C, Yamauchi K, Yagi Gobei, Asai M, Kanaba S. Prediction of medication noncompliance in outpatient with schizophrenia: 2-year follow-up study. Psychiatry Res. 2006; 14: 61-69.
60.Yen CF, Chen CS, Ko CH, Yeh ML, Yang SJ, Yen JY, Huang CF, Wu CC. Relationships between insight and medication adherence in outpatients with schizophrenia and bipolar disorder: prospective study. Psychiatry Clin. Neurosci. 2005; 59(4): 403-409.
61.洪佳偉．抗精神病藥物於精神分裂症患者之使用評估．國立成功大學臨床藥學研究所碩士論文，2005。
62.鄭湘茹．精神分裂症患者服藥遵從行為與服藥種類副作用及症狀之相關研究．慈濟大學護理研究所碩士論文，2003。
63.黃瑞媛．服用非傳統抗精神病藥物之精神分裂症病患對藥物態度及其相關因素探討．國立台灣大學護理學研究所碩士論文， 2000。
64.Lieberman JA, Perkins D, Belger A, Chakos M, Jarskog F, Boteva K, Gilmore J. The early stages of schizophrenia: speculations on pathogenesis, pathophysiology and therapeutic approaches. Biol. Psychiatry 2001; 50(11): 884-897.
65.David A, Buchanan A, Reed A, Almeida O. The assessment of insight in psychosis. Br. J. Psychiatry 1992; 161: 599-602.
66.Simmons S. Social networks: their relevance to mental health nursing. J. Adv. Nurs. 1994; 19: 281-289.
67.藍菊梅、林信男、蕭淑貞．精神分裂症服藥結盟行為之預測因子． 台灣精神醫學，2004，18(3)，200-206。
68.藍菊梅．精神分裂症的治療結盟行為及其相關因素探討．國立台灣大學護理學研究所碩士論文，1996。
69.Amador XF, Strauss DH, Yale SA. Awareness of illness in schizophrenia. Schizophr. Bull. 1991; 17: 113-132.
70.Thompson K, Kulkarni J, Sergejew AA. Reliability and validity of a new Medication Adherence Rating Scale (MARS) for the psychoses. Schizophr. Res. 2000; 42: 241-247.
71.黃瑞琦．社區精神分裂症病患之病識感、社會支持度與生活適應．高雄醫學大學護理學研究所碩士論文，2001。
72.劉玉雲．精神分裂症病患之疾病不確定感及相關因素探討．國立台灣大學護理學研究所碩士論文，1998。
73.Norbeck JS, Lindesy AM, Carrieri VL. The development of an instrument to measure social support. Nurs. Res. 1981; 30(5): 264-269.
74.David AS. Insight and psychosis. Br. J. Psychiatry 1990; 156: 798-808.
75.楊淑瑜．精神分裂症病患的處方模式-多重用藥及不良反應．高雄醫學大學醫學研究所博士論文，2007。
76.Diaz E, Neuse E, Sullivan MC, Pearsall HR, Woods SW.Adherence to conventional and atypical antipsychotics after hospital discharge. J. Clin. Psychiatry 2004; 65(3): 354-360.
77.Menzin J, Boulanger L, Friedman M, Mackell J, Lioyd JR. Treatment adherence associated with conventional and atypical antipsychotics in a large state Medicaid program. Psychiatry Serv. 2003; 54(5): 337-339.
78.Amador XF, Flaum M, Andreasen NC, Strauss DH, Yale SA, Clark SC, Gorman JM. Awareness of illness in schizophrenia and schizoaffective and mood disorders. Arch. Gen. Psychiatry 1994; 51(10): 826-836.
79.David A, Buchanan A, Reed A, Almedida O. The Assessment of insight in psychosis. Br. J. Psychiatry 1992; 161: 599-602.
80.Smith TE, Hull JW, Israel LM, Wilson DF. Insight, symptoms and neurocognition in schizophrenia and schizoaffective disorder. Schizophr. Bull. 2000; 26(1): 193-200.
81.林立寧、何曉旭、謝明憲．第二代抗精神病藥物對精神分裂症患者病識感的影響．台灣醫學，2004，8(3)，411-415。
82.Day JC, Wood G, Dewey M, Bentall RP. A self-rating scale for measuring neuroleptic side-effects, Validation in a group of schizophrenia patients. Br. J. Psychiatry 1995; 166: 650-653.