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研究生： 張惠華
Chang, Hui-Hua
論文名稱： Lithium與Valproate對雙極性疾患病人血糖、血脂、體重影響之研究
Effects of Lithium and Valproate on Blood Sugar, Blood Lipids, and Body Weight in Bipolar Patients
指導教授： 陳柏熹
Chen, Po-See
周辰熹
Chou, Chen-Hsi
林嘉音
Lin, Chia-Yin
楊延光
Yang, Yen-Kuang
學位類別： 碩士
Master
系所名稱： 醫學院 - 臨床藥學研究所
Institute of Clinical Pharmacy
論文出版年： 2007
畢業學年度： 95
語文別： 英文
論文頁數： 120
中文關鍵詞： 體重 、血脂 、血糖 、雙極性疾患 、鋰鹽 、情緒穩定劑 、代謝症候群
外文關鍵詞： blood sugar, body weight, blood lipid, bipolar disorder, valproate, lithium, metabolic syndrome, mood stabilizers
相關次數： 點閱：270  下載：5 
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    • 研究目的：本研究為調查於門診追蹤之雙極性疾患病人，在使用情緒穩定劑（以lithium和valproate為主）情況下，其血糖、血脂、體重與代謝症候群之盛行率。
    研究方法：本研究為橫斷面研究，自民國九十五年三月一日至九十六年二月二十八日期間，於國立成功大學附設醫院精神科門診追蹤治療之雙極性疾患且使用情緒穩定劑的病患為對象，主要調查患者之血糖、血脂、或體重異常之情況，並進一步以國際糖尿病協會訂定之標準評估代謝症候群之盛行率。
    研究結果：共有117位病患納入分析，其中有16位(13.7%)有高血糖，43位(36.8%)的三酸甘油脂過高，而有62位(53.0%)的高密度膽固醇過低，36位(61.0%)有腹部肥胖，11位(18.6%)有高血壓；共有20位病患符合代謝症候群之條件。利用邏輯性回歸分析，控制其他危險因子計算勝算比(odds ratio；OR)後發現，過去三個月和三至六個月暴露於非典型抗精神病藥物之代謝症候群的OR分別為1.687 (95% CI: 0.382- 7.442)和1.393 (95% CI: 0.237- 8.177)；在情緒穩定劑方面，以valproate為指標，使用lithium之OR為1.585 (95% CI: 0.266- 9.449)，而合併lithium和valproate的OR為15.507 (95% CI: 0.958- 251.011)。
    結論：與一般大眾相比，雙極性疾患病人之血糖、血脂、體重異常比例，和代謝症候群之盛行率均較高。因此，醫療照護者對於藥物在臨床使用治療外，應額外注意其可能出現代謝異常之不良反應，尤其是合併使用兩種情緒穩定劑之患者。

    Objective: This study is to evaluate the presence of the metabolic syndrome in a group of 117 outpatients with bipolar disorder treated with mood stabilizers in Taiwan.
    Method: This was a cross-sectional study. We collected data from follow-up participants at psychiatric outpatient clinics. We focused on the presence of the metabolic syndrome, as defined by the 2005 International Diabetes Foundation (IDF) criteria.
    Results: We found that 33.9% of the patients met the IDF 2005 criterion for the metabolic syndrome, that 61.0% of them met the criterion for abdominal obesity, 36.8% for hypertriglyceridemia, 53.0% for lower high-density lipoprotein cholesterol, 18.6% for hypertension or on hypertension medications, and 13.7% for high fasting glucose or received antidiabetic medications. Through logistic regression model in subgroup analysis of metabolic syndrome, we found that exposing to the second generation antipsychotics (SGAs) in the past 3 or 3-6 months was not regarded as a significant predictor factor. The odds ratio of the SGAs were 1.687 and 1.393, respectively. We found that monotherapy with mood stabilizer contributed to metabolic syndrome as equal as the SGAs, and that once patients were treated with combined lithium and valproate therapy, the odds ratio of metabolic syndrome was increased to 15.507 (p=0.054).
    Conclusion: This study indicates that the metabolic syndrome is highly prevalent in patients with bipolar disorder. Physicians should be aware that the treatment of bipolar disorder involves the risk-benefit balance for patients in terms of adverse effects such as metabolic abnormalities. Based on the finding of this study, we suggest that the practicing psychiatrists and primary care professionals need to monitor the parameters which are included in the metabolic syndrome to identify those patients with an increased risk for cardiovascular diseases.

    中文摘要..............................................Ⅰ Abstract..............................................Ⅲ 誌謝..................................................Ⅴ Contents............................................ⅤⅡ Table of Contents...................................ⅩⅣ Figure of Contents..................................ⅩⅥ Abbreviation........................................ⅩⅦ Part A. Effects of lithium and valproate on blood sugar, blood lipid, and body weight in bipolar patients……………..……………………..1 1. Background review................................1 1.1 Bipolar disorder................................1 1.2 Current pharmacologic treatment of bipolar disorder..................................................7 1.2.1 During manic phase...............................7 1.2.2 During depressive phase..........................7 1.2.3 During maintenance phase........................11 1.3 Metabolic syndrome..............................13 1.4 Medical disorders related to pharmacologic treatment of bipolar disorder.............................20 1.4.1 Obesity.............................................20 1.4.2 Abnormal blood sugar..........................21 1.4.3 Polycystic ovarian syndrome.........................21 1.4.4 Hypothyroidism......................................22 2. Objectives of current study...........................23 3. Method................................................24 3.1 Study Design.......................................24 3.2 Subjects and method................................24 3.3 Measurement........................................24 3.3.1 Blood...............................................24 3.3.1.1 Blood sugar profile...............................24 3.3.1.2 Blood lipid profile...............................25 3.3.1.3 Drug concentration................................25 3.3.1.4 Leptin............................................25 3.3.2 Blood pressure......................................25 3.3.3 Adiposity and body fat distribution.................25 3.3.4 The definition of metabolic syndrome................26 3.4. Statistical analysis.................................26 4. Results.........................................27 4.1 Demographic characteristics and clinical features.....27 4.2 Measurement...........................................28 4.2.1 Blood sugar profiles................................28 4.2.2 Blood lipid profiles................................28 4.2.3 Body weight.........................................28 4.2.4 Blood pressure......................................28 4.2.5 Prevalence of metabolic syndrome....................29 4.3 Pharmacotherapy pattern...............................30 4.3.1 Medications in treatment of bipolar disorder........30 4.3.2 Demographic characteristics and clinical features...30 4.3.2.1 In Li ............................................30 4.3.2.2 In VPA............................................31 4.3.2.3 In Li plus VPA....................................31 4.3.2.4 Compared demographic characteristics and clinical features between three groups.............................31 4.3.3 Measurement of blood profiles.......................32 4.3.3.1 Blood sugar profiles..............................32 4.3.3.1.1 In Li ..........................................32 4.3.3.1.2 In VPA..........................................32 4.3.3.1.3 In Li plus VPA..................................32 4.3.3.1.4 Compared blood sugar between three groups.......33 4.3.3.2 Blood lipid profiles..............................33 4.3.3.2.1 In Li...........................................33 4.3.3.2.2 In VPA..........................................33 4.3.3.2.3 In Li plus VPA..................................33 4.3.3.2.4 Compared blood lipid between three groups.......34 4.3.4 Body weight.........................................34 4.3.4.1 In Li.............................................34 4.3.4.2 In VPA............................................34 4.3.4.3 In Li plus VPA....................................35 4.3.4.4 Compared body weight between three groups.........35 4.3.5 Blood pressure......................................35 4.3.5.1 In Li.............................................35 4.3.5.2 In VPA............................................35 4.3.5.3 In Li plus VPA....................................36 4.3.5.4 Compared blood pressure between three groups......36 4.4 The effects of second generation antipsychotics.......37 4.4.1 Demographic characteristics and clinical features...37 4.4.1.1 In using second generation antipsychotics group...37 4.4.1.2 In non-using second generation antipsychotics group.....................................................37 4.4.1.3 Compared demographic characteristics and clinical features between groups...................................38 4.4.2 Measurement blood profiles..........................38 4.4.2.1 Blood sugar profiles..............................38 4.4.2.1.1 In using second generation antipsychotics group.....................................................38 4.4.2.1.2 In non-using second generation antipsychotics group.....................................................38 4.4.2.1.3 Compared blood sugar between groups.............38 4.4.2.2 Blood lipid profiles..............................38 4.4.2.2.1 In using second generation antipsychotics group.....................................................38 4.4.2.2.2 In non-using second generation antipsychotics group.....................................................39 4.4.2.2.3 Compared blood lipid between groups.............39 4.4.3 Body weight.........................................39 4.4.3.1 In using second generation antipsychotics group...39 4.4.3.2 In non-using second generation antipsychotics group....................................................40 4.4.3.3 Compared body weight between groups..............40 4.4.4 Blood pressure.....................................40 4.4.4.1 In using second generation antipsychotics group..40 4.4.4.2 In non-using second generation antipsychotics group....................................................40 4.4.4.3 Compared blood pressure between groups...........40 4.4.5 Prevalence of metabolic syndrome...................41 4.5 Prevalence of metabolic syndrome.....................42 4.5.1 Demographic characteristics and clinical features..42 4.5.1.1 In patients with metabolic syndrome..............42 4.5.1.2 In patients without metabolic syndrome...........42 4.5.1.3 Compared demographic characteristics and clinical features.................................................43 4.5.2 Measurement of blood profiles......................43 4.5.2.1 Blood sugar profiles.............................43 4.5.2.1.1 In patients with metabolic syndrome............43 4.5.2.1.2 In patients without metabolic syndrome.........43 4.5.2.2 Blood lipid profiles.............................43 4.5.2.2.1 In patients with metabolic syndrome............43 4.5.2.2.2 In patients without metabolic syndrome.........44 4.5.3 Body weight........................................44 4.5.3.1 In patients with metabolic syndrome..............44 4.5.3.2 In patients without metabolic syndrome...........44 4.5.4 Blood pressure.....................................44 4.5.4.1 In patients with metabolic syndrome..............44 4.5.4.2 In patients without metabolic syndrome...........44 4.6 Predictors for measurements and metabolic syndrome...46 4.6.1 Blood sugar .......................................46 4.6.2 Blood lipid........................................46 4.6.2.1 TG...............................................46 4.6.2.2 HDL-C............................................47 4.6.3 Waist circumference................................47 4.6.4 Blood pressure.....................................47 4.6.5 Metabolic syndrome.................................48 4.7 Correlation between drug serum concentration and prescription.............................................49 4.7.1 In Li group........................................49 4.7.2 In VPA group.......................................49 5. Discussion............................................73 5.1 The prevalence of metabolic abnormalities............73 5.1.1 The prevalence of hyperglycemia....................73 5.1.2 The prevalence of abnormal blood lipid.............73 5.1.3 The prevalence of abnormal body weight.............74 5.1.4 The prevalence of hypertension.....................74 5.1.5 The prevalence of metabolic syndrome...............74 5.2 Contribution of metabolic syndrome among bipolar patients.................................................76 5.2.1 Bipolar disorder...................................76 5.2.2 Lifestyle..........................................77 5.3 Effects of medications on metabolic syndrome.........78 5.3.1 Mood stabilizers ..................................78 5.3.2 Second generation antipsychotic drug...............79 5.4 Drug compliance in bipolar patients..................82 5.5 Health care impact...................................84 5.5.1 Influence of mood stabilizers-induced metabolic abnormalities............................................84 5.5.2 Monitor for metabolic abnormalities associated with mood stabilizers.........................................84 5.5.3 Alternative strategies of treatment in bipolar patients.................................................86 5.6 Future work..........................................88 5.7 Limitation...........................................89 6. Conclusion............................................92 7. Reference…...........................................93 Part B. 臨床藥事服務-雙極性疾患藥物之衛教……………………105 第一章 目的………………………………………………………105 第二章 方法………………………………………………………106 第三章 記錄方式…………………………………………………107 第四章 結果………………………………………………………110 第五章 結語………………………………………………………113 附錄……………………………………………………………………114 附錄一、雙極性疾患之衛教單張……………………………………114 附錄二、鋰鹽藥物之衛教單張………………………………………116 附錄三、帝拔癲藥物之衛教單張……………………………………118

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