https://scholars.lib.ntu.edu.tw/handle/123456789/112348
DC 欄位 | 值 | 語言 |
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dc.contributor | 賴美淑 | en |
dc.contributor | 臺灣大學:預防醫學研究所 | zh_TW |
dc.contributor.author | 詹宏裕 | zh |
dc.contributor.author | Chan, Hung-Yu | en |
dc.creator | 詹宏裕 | zh |
dc.creator | Chan, Hung-Yu | en |
dc.date | 2006 | en |
dc.date.accessioned | 2007-11-28T01:23:47Z | - |
dc.date.accessioned | 2018-06-29T17:52:39Z | - |
dc.date.available | 2007-11-28T01:23:47Z | - |
dc.date.available | 2018-06-29T17:52:39Z | - |
dc.date.issued | 2006 | - |
dc.identifier | zh-TW | en |
dc.identifier.uri | http://ntur.lib.ntu.edu.tw//handle/246246/59234 | - |
dc.description.abstract | 背景:第一代抗精神病藥物常會產生錐體外路徑副作用(EPS),臨床上常會使用第二代抗精神病藥物來加以取代,但是要轉換為何種第二代抗精神病藥物,過去的研究或是各國的治療指引結論不一,而且也沒有華人的轉換研究。本研究以隨機分配有對照組的研究,來比較risperidone以及olanzapine這兩種第二代抗精神病藥物,對於無法耐受第一代抗精神病藥物所產生錐體外路徑副作用中的急性肌張力異常或巴金森氏症,轉換後其發生急性肌張力異常或巴金森氏症且需使用抗膽鹼藥物來加以治療的比例是否有所差別。另外收集risperidone及 olanzapine在不同時間點的平均劑量變化,來作為擬定此類病患的起始劑量、加藥速度及維持劑量的參考。 方法: 本研究是由行政院衛生署桃園療養院在民國八十九年七月至九十二年五月期間收案。對象是符合DSM-IV schizophrenia的精神分裂症診斷標準,並且發生符合DSM-IV neuroleptic-induced acute dystonia or parkinsonism診斷標準的副作用,且其嚴重度達到global impression of dystonia or parkinsonism of ESRS (extrapyramidal syndrome rating scale)的中度以上所有個案。並符合以下條件:女性必須同意試驗期間避孕;年齡18-65歲;個案或法定代理人同意參加研究且簽署同意書。排除條件為個案目前有DSM-IV其他第一軸的診斷;個案目前有主要系統性身體疾病,或需併用相關治療藥物,而無法配合研究藥物之治療及評估;個案目前有相關神經學疾病而影響錐體外路徑副作用評估;個案一年內除香煙及咖啡外,有其它物質濫用或依賴的診斷。共收案70人,以隨機分配的方式分派到risperidone或olanzapine,兩組各35人。個案研究期間最長為八週,因此研究結束時間為九十二年七月。本研究為任意劑量評分者單盲的研究,risperidone的平均起始劑量為1.8 mg/d,之後逐漸增加到研究結束的平均劑量為3.5 mg/d,olanzapine的平均起始劑量為7.7 mg/d,之後逐漸增加到研究結束的平均劑量為11.7 mg/d。主要的研究變項包括發生顯著acute dystonia或parkinsonism副作用而需使用抗膽鹼藥物的比例,ESRS評量表以測量錐體外路徑副作用的嚴重度,BPRS(brief psychiatric rating scale)以及CGI-S(clinical global impression-severity)評量表以評估精神症狀的嚴重度。以Chi-square 或Fisher’s exact test來比較兩組使用抗膽鹼藥物的比例及其他binominal data是否有統計上的差異;若考慮使用抗膽鹼藥物發生的時間以及存活的狀態,則以Kaplan-Meier method以及Cox regression來加以分析;以independent t-test來比較兩組間之研究起始與研究結束連續性變項的改變程度是否有統計上的差異;精神症狀評量表重複測量的資料將以mixed model for repeated measurement處理。 結果:使用研究藥物後發生顯著acute dystonia或parkinsonism副作用而需使用抗膽鹼藥物,risperidone組顯著高於olanzapine組(OR=5.17, 95%CI=1.49-17.88, p=0.013);以存活資料來分析,發生事件的機率risperidone組仍顯著高於olanzapine組(log-rank test: p=0.0023; hazard ratio: 4.60, 95% CI: 1.70-11.52)。分析精神症狀的改善幅度,兩組並無統計顯著差異。 結論:本研究結果支持以olanzapine來作為此類病患的優先選擇,與英國的Maudsley prescription guideline建議使用第二代抗精神病藥物於此類病患仍應有科學證據做為優先選擇之參考的論點一致。 | zh_TW |
dc.description.abstract | Background: First genergation antipsychotics frequently induced extrapyramidal side effects(EPS). Second generation antipsychotics were the choices for EPS intolerant schizophrenic patients. But which one of second generation antipsychotic was the better choice did not have definitive results. There was no such shifting study in Chinese populations. We wish to establish local data to help clinical decision in such patients by a well designed randomized controlled trial. We used risperidone and olanzapine in schizophrenic patients with acute dystonia or parkinsonism side effects and copmared the incidence of needing concomitat anticholinergic drugs. We also collected the average dose in different assessment periods of risperidone and olanzapine to establish the dosing strategy guidelines for EPS intolerant schizophrenic patients. Materials and Methods: We collected patients at Taoyuan Mental Hospital since July 2000 to May 2003. The target populations of this study were patients met the schizophrenia criteria of DSM-IV. Patients also needed to meet the research criteria of neuroleptic-induced acute dystonia or parkinsonism research criteria of DSM-IV and greater than moderate severity of global impression of dystonia or parkinsonism of extrapyramidal syndrome rating scale(ESRS). The inclusion criteria were(1)Female patients need to use reliable methods to prevent preganacy(2)Age between 18-65 y/o(3)Patients or legal responsible person agree to attend study and sign inform consent. The exclusion criteria were(1)Have other axis I diagnosis of DSM-IV(2)Have major systemic disease and influence to assessment or the use of study medications(3)Have neurological disease and influence to assessment of EPS(4)Have substance abuse or dependence in recent 1 year except tobacco or coffee. The total numbers of pateints were 70 and random assignment to risperidone or olanzapine. This study ended at July 2003 due to the study period was 8 weeks. This is a flexible dose, rater-blinded, randomized, controlled trial. The average dose of risperidone and olanzapine from baseline to study end point were 1.8 to 3.5 mg/d and 7.7 to 11.7 mg/d respectively. The primary outcome was to compare the incidence of concomitant anticholinergics to manage acute dystonia or parkinsonism in these 2 groups. The secondary outcomes were to comapre the results of rating scales in these 2 groups. The severity of EPS was assessed by ESRS. The severity of psychotic symptoms was assessed by BPRS (brief psychiatric rating scale) and CGI-S (clinical global impression-severity). The statistical methods included Chi-square or Fisher’s exact test for binominal data, Kaplan-Meier method or Cox regression for survival data, independent or paired t-test for continous variables, mixed model for repeated measures. Results: Risperidone had significant higher incidence to use anticholinergics to manage acute dystonia or parkinsonism(OR=5.17, 95%CI=1.49-17.88, p=0.013). Risperidone also had significant higher incidence to use anticholinergics to manage acute dystonia or parkinsonism if consider time and censor cases(log-rank test: p=0.0023; hazard ratio: 4.60, 95% CI: 1.70-11.52). There was no significant difference in change of psychotic symptoms. Conclusion: The results of our study favor olanzapine as better choice for schizophrenic patients with acute dystonia or parkinsonism side effects. This result was compatible with the suggestion of Maudsley prescription guideline of United Kingdom as some second generation antipsychotics as priority choice for EPS sensitive populations. | en |
dc.description.tableofcontents | 中文摘要 8 English Abstract 11 1. 前言 15 1.1. 背景 15 1.2. 目的 17 2. 文獻回顧 18 2.1. 抗精神病藥物的演進及作用機轉 18 2.2. 抗精神病藥物引發錐體外路徑副作用 21 2.2.1. 分類及診斷標準 21 2.2.2. 評估工具 22 2.2.3. 嚴重度的判定及需使用抗膽鹼藥物的時機 25 2.3. 抗精神病藥物引發急性肌張力異常或巴金森氏症 28 的危險因子以及過去處理的問題 2.4. Risperidone 和olanzapine之相關臨床試驗 30 2.4.1. 第三期臨床試驗劑量與療效及副作用的結果 30 2.4.2. 一般精神分裂症病患比較性試驗結果 31 2.4.3. 錐體外路徑副作用研究的結果 32 2.5. 錐體外路徑副作用的治療指引 34 2.6. 文獻回顧整理及未解決的問題 35 3. 材料及方法 37 3.1. 研究族群及收案標準 37 3.2. 研究進行方式 39 3.2.1. 隨機分派過程及評估者單盲的方法 39 3.2.2. 研究過程及參與者流程圖 40 3.2.3. 研究藥物劑量及禁止併用藥物 41 3.3. 評量工具及療效指標的測量 42 3.4. 統計方法及樣本數估算 44 4. 結果 46 4.1. 研究族群之描述性資料分析 46 4.2. 研究藥物劑量 47 4.3. 研究藥物對精神症狀的療效及 48 錐體外路徑副作用的變化 4.3.1. 精神症狀的療效 48 4.3.2. 錐體外路徑副作用的變化 49 4.4. 藥物不良反應之分析及其他併用藥物 51 5. 總結及討論 53 5.1. 總結 53 5.2. 討論 54 5.2.1. 評量工具測量結果與併用藥物結果的差異 54 5.2.2. 精神分裂症病患出現急性肌張力異常或 55 巴金森氏症副作用的劑量問題 5.2.3. 與過去研究結果的比較 55 5.2.4. 本研究的優點及限制 56 參考文獻 58 表 65 圖 84 附錄 87 | zh_TW |
dc.format.extent | 791250 bytes | - |
dc.format.mimetype | application/pdf | - |
dc.language | zh-TW | en |
dc.language.iso | en_US | - |
dc.subject | 抗精神病藥物 | en |
dc.subject | 精神分裂症 | en |
dc.subject | 錐體外路徑副作用 | en |
dc.subject | antipsychotic | en |
dc.subject | schizophrenia | en |
dc.subject | extrapyramidal side effects | en |
dc.subject.classification | [SDGs]SDG3 | - |
dc.title | 藥物引發急性肌張力異常或巴金森氏症之精神分裂症病患對Risperidone及Olanzapine的隨機分配對照研究 | zh |
dc.title | A Randomized Controlled Trial study of Risperidone and Olanzapine for the Schizophrenic Patients with Neuroleptic-induced Acute Dystonia or Parkinsonism | en |
dc.type | thesis | en |
dc.identifier.uri.fulltext | http://ntur.lib.ntu.edu.tw/bitstream/246246/59234/1/ntu-95-R93846010-1.pdf | - |
dc.relation.reference | 1. Chouinard G, Johns B, Remington G, et al.: A Canadian multi-center placebo-controlled study of fixed dose of risperidone and haloperidol in the treatment of chronic schizophrenia. J Clin Psychopharmacol 1993; 13:25-40 2. Marder SR, Meibach RC:Risperidone in the treatment of schizophrenia.Am J Psychiatry 1994;151(6);825-835 3. Peuskens P: Risperidone in the treatment of patients with chronic schizophrenia. Br J Psychiatry 1995; 166: 712-26 4. Beasley CM, Tollefson GD, Tran PV, et al.: Olanzapine versus placebo and haloperidol: acute phase results of the North American double-blind olanzapine trial. Neuropsychopharmacology 1996; 14: 111-23 5. Beasley CM, Hamilton SH, Crawford AM, et al.: Olanzapine versus haloperidol: acute phase results of the international double-blind olanzapine trial. Eur Neuropsychopharmacol 1997; 7: 125-37 6. Tollefson GD, Beasley CM, Tran PV: Olanzapine versus haloperidol in the treatment of schizophrenia and schizoaffective and schizophreniform disorders. Am J Psychiatry 1997; 154: 457-65 7. Heck AH, Haffmans PM, De Groot IW , et al: Risperidone versus holoperidol in psychotic patients with disturbing neuroleptic-induced extrapyramidal symptoms:a double-blind , multi-center trial . Schizo Res 2000 Dec 15;46(2-3);97-105 8. Costa e Silva JA, Alvarez N, Mazzotti G, et al. Olanzapine as alternative therapy for patients with haloperidol-induced extrapyramidal symptoms. J Clin Psychopharmacol 2001: 21; 375-81 9. Lane HY, Lin HN, Hwu HG, et al. Haloperidol plasma concentrations in Taiwanese psychiatric patients. J Formosan Med Association 1995;94:671-678 10. Lin KM, Poland RE, Lau JK, et al. Haloperidol and prolactin concentrations in Asians and Caucasians. J Clin Psychopharmacol 1988;8:195-201 11. American psychiatric association:Practice guideline for the treatment of schizophrenia patients. Second edition, 2004 12. The south London and Maudskey NHS trust: The Mandsley 2003 prescribing guidelines. Seventh edition, 2003 13. Compton WM 3rd, Helzer JE, Hwu HG, et al.: New methods in cross-cultural psychiatry: psychiatric illness in Taiwan and the United States. Am J Psychiatry 1991;148:1697-1704 14. Bunney WE, Meltzer HY. Schizophrenia: overview. Clin Neurosci 1995;3:55-56 15. Creese I, Burt DR, Snyder SH. Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science 1976;192:481-483 16. Richelson E. Receptor pharmacology of neuroleptics; relation to clinical effects. J Clin Psychiatry 1999;60(suppl 10):5-14 17. Meltzer HY. Treatment of the neuroleptic-nonresponsive schizophrenic patients. Schizophr Bull 1992;18:515-542 18. Casey DE: Neuroleptic drug-induced extrapyramidal syndromes and tardive dyskinesia. Schizophr Res 1991;4:109-130 19. Ayd Fj Jr: A survey of drug-induced extrapyramidal reactions. JAMA 1961; 75:1054-60 20. Gupta S, Mosnik D, Black DW, et al: Tardive dyskinesia: Review of treatments past, present, and future. Annals of clinical psychiatry 1999; 11(4):257-66. 21. Weiden PJ, Miller AL: Which side effects really matter? Screening for common and distressing side effects of antipsychotic medications. J Psych Pract 2001; 7:41-7 22. Kane J, Honigfeld G, Singer J, Meltzer H: Clozapine for the treatment-resistant schizophrenia. Arch Gen Psychiatry 1988; 45: 789-96 23. Glazer WM: Extrapyramidal side effects, tardive dyskinseia, and the concept of atypicality. J Clin Psychiatry 2000; 61(suppl 3): 16-21 24. Huttunen M: The evolution of the serotonin-dopamine antagonist concept. J Clin Psychopharmacol 1995;15(suppl 1):4-10 25. Kinon BJ, Lieberman JA. Mechanisms of action of atypical antipsychotic drugs: a critical analysis. Psychopharmacology 1996;124:2-34 26. Seeman P, Tallerico T: Antipsychotic drugs which elicit little or no parkinsonism bind more loosely than dopamine to brain D2 receptors, yet occupy high levels of these receptors. Mol Psychiatry 1998;3:123-134 27. Stahl SM. Psychopharmacology of antipsychotics. 1999. 28. Lane RF. Blaha CD. Rivet JM: Selective inhibition of mesolimbic dopamine release following chronic administration of clozapine. Brain Research. 460(2):398-401, 1988 Sep 20 29. Caroff SN, Mann SC, Campbell EC, et al: Movement disorder associated with atypical antipsychotic drugs. J Clin Psychiatry 2002; 63(suppl 4): 12-19 30. Sharma T. Antonova L: Cognitive function in schizophrenia. Deficits, functional consequences, and future treatment. Psychiatric Clinics of North America 2003;26:25-40 31. Awad AG, Voruganti LN: Impact of atypical antipsychotics on quality of life in patients with schizophrenia. CNS Drugs 2004;18:877-893 32. American psychiatric association: Diagnostic and statistical manual of mental disorders. Fourth edition, 735-749 33. World Health Organization: The ICD-10 Classification of Diseases of Nervous System. World Health Organization 1992 34. Simpson GM, Angus JWS: A rating scale for extrapyramidal side effects. Acta Psychiatr Scand 1970; 212: 9 35. Chouinard G, Ross-Chouinard A, Annable L, et al: The extrapyramidal symptom rating scale. Can J Neurol Sci 1980; 7: 233 36. Chouinard G, Margolese HC. Manual for the extrapyramidal symptom rating scale (ESRS). Schizo Res 2005;76:247-65 37. Chouinard G, Ross-Chouinard A, Gauthier S, et al. An extrapyramidal rating scale for idiopathic and neuroleptic-induced Parkinsonism and dyskinesia. CINP 14th congress 1984, Book of abstracts, p.16. 38. Chouinard G, Annable L, Mercier P, et al. Long-term effects of L-dopa and procyclidine on neuroleptic-induced extrapyramidal and schizophrenic symptoms. Psychopharmacol Bull 1987;9;247-253. 39. Tran PV, Hamilton MS, Susan H, et al: Double-blind comaprison of olanzapine versus risperidone in the treatment of schizophrenia. J Clin Psychopharmacol 1997; 17: 408-18 40. Conley RR, Mahmoud R: A randomized-double blind study of risperidone and olanzapine in the treatment of schizophrenia. Am J Psychiatry 2001; 158: 765-74 41. Lippincott Williams & Wilkins: Synopsis of Psychiatry. Ninth edition, 2003 42. Bondolfi G, Dufour H, Patris M, et al.: Risperidone versus clozapine in treatment-resistant chronic schizophrenia: a randomized double-blind study. Am J Psychiatry 1998 ; 155: 499-504 43. Guy W: ECDEU Assessment manual for psychopharmacology -revised 1976: 218-22 44. Overall JE, Gorham DR: The brief psychiatric rating scale (BPRS). Psychopharmacol Bull 1988; 24: 97-9 45. Kasper S: Risperidone and olanzapine: optimal dosing for efficacy and tolerability in patients with schizophrenia. Int Clin Psychopharmacol 1998; 13: 253-62 46. Natioal Disease and Therapeutic Index. Plymouth meeting, Penn., IMS America, Jun 1999 47. Robinowitz J, Lichtenberg P, Kaplan Z. Comparison of cost, dosage and clinical preference for risperiodne and olanzapine. Schizophr Res 2000;46:91-6 | en |
item.languageiso639-1 | en_US | - |
item.cerifentitytype | Publications | - |
item.fulltext | with fulltext | - |
item.openairecristype | http://purl.org/coar/resource_type/c_46ec | - |
item.openairetype | thesis | - |
item.grantfulltext | open | - |
顯示於: | 流行病學與預防醫學研究所 |
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