肥胖相關代謝性疾患家族史作為精神分裂症病患接受抗精神病藥物出現肥胖相關代謝變化之危險因子

Family history of obesity related metabolic diseases as the risk factor of metabolic disturbances in schizophrenic patients receiving antipsychotics

陳柏妤(Po-Yu Chen)

指導教授 ： 楊偉勛

國立臺灣大學/醫學院/臨床醫學研究所/碩士(2008年)

https://doi.org/10.6342/NTU.2008.01590

摘要

目的
肥胖及糖尿病是抗精神病物用於治療精神分裂症病患常見的副作用，並且可能導致病患產生心血管疾病及降低對服藥的順從型。許多國外文獻顯示精神分裂症病患肥胖、代謝症候群、糖尿病的盛行率均較一般族群為高。國內則較缺乏針對社區精神病患代謝疾病之盛行率調查。目前證據顯示，不同的抗精神病藥物之引發不同代謝變化的效應已被廣泛討論。然而，針對病患本身之臨床危險分子之探討則相對不足。家族史在一般族群中以被認為是病患產生代謝疾患的重要危險因子。然而，目前仍缺乏針對代謝疾病家族史是否為抗精神病藥物治療精神分裂症病患引發代謝疾患之危險因子之研究。本研究希望提供國內社區精神病患代謝疾病之盛行率之參考。並針對代謝疾病家族史探討其對於抗精神病藥物治療精神分裂症病患引發代謝疾患之影響。
方法
配合台北市衛生局社區病患健康篩檢活動，邀請居住於台北市社區及康復之家之精神分裂症病患自願加入本研究。進行臨床資料訪視、身體指標測量、及抽血。計算代謝及患之盛行率。並以回歸分析方式檢驗代謝疾病家族史對於抗精神病藥物治療精神分裂症病患引發代謝疾患之影響。
結果
總計307位病患加入本研究並完成收案。本研究發現社區精神分裂症病患之過重者高達約60%，肥胖者亦占約30%。代謝症候群人數約佔33.01%。高血壓者占33.66%；糖尿病者占10.46%；高血總膽固醇者占9.48%。代謝疾病盛行率均較一般族群為高。男性之高血壓比例較高，而女性之糖尿病、腹部肥胖比例較高。本研究中，傳統藥物、第二代抗精神病藥物或第三代抗精神病藥物對於代謝變化並無顯著不同之影響。針對代謝疾病家族史之分析則發現在調整年齡、性別、藥物等因素後，糖尿病家族史是唯一獨立的危險因子，其將提高病患接受抗精神病藥物產生過重的風險至2.35倍，肥胖的風險至2.01倍，腹部肥胖的風險至2.07，而糖尿病的風險至3.31倍。此外，糖尿病家族史將平均增加病患體重約4.95公斤（p=0.019），並提高身體質量指數達2.11 kg/m2（p=0.005）。因此可以作為精神分裂症病患接受抗精神病藥物產生過重、肥胖、腹部肥胖、糖尿病的預測因子，提供抗精神病藥物選擇時之參考。此外，本研究亦發現藥物種類與糖尿病家族史存在交互作用。傳統藥物、第二代抗精神病藥物在有糖尿病家族史之病患引發更顯著之腹部肥胖風險。至於其他代謝疾病家族史則與精神分裂症病患接受抗精神病藥物出現代謝疾病之風險高低無顯著之關係。在研究限制方面，本研究僅取得病患目前之抗精神病藥物史。並且由於藥物種類繁多，無法就單一藥物之效應進行討論。此外，家族史來自病患之自我報告，由於精神病患之認知功能不足，家族史可能被低估。
結論
社區精神分裂症病患代謝疾病盛行率較一般族群為高。並且存在性別間之差異。糖尿病家族史可預測病患接受抗精神病藥物產生較高過重、肥胖、腹部肥胖及糖尿病的風險。

關鍵字

精神分裂症 ； 抗精神病藥物 ； 肥胖 ； 糖尿病 ； 代謝症候群 ； 危險因子 ； 家族史

並列摘要

Objective:
Obesity and diabetes mellitus are common side effects during antipsychotics treatment. These side effects may predispose cardiovascular diseases and decrease antipsychotics compliance in schizophrenic patients. Higher prevalence of metabolic diseases in schizophrenic patients was frequently reported in many countries. However, there are not many studies of the prevalence of metabolic diseases in community patients in Taiwan. Different effects on metabolic disease among various antipsychotics have been broadly discussed. However, clinical risk factors focusing on patient aspects still need to be further clarified. Family history was demonstrated as an important risk factor for metabolic diseases in general population. However, whether family history us also important for antipsychotics related metabolic disease is still an unresolved question. Our study aimed to provide reference for prevalence of metabolic disease in community schizophrenic patient in our country. Furthermore, this study examined the influence of family history on the metabolic outcomes related to antipsychotics treatments
Methods:
Volunteer schizophrenic patients were recruited during a disease screening activity, sponsored by Taipei Public Health Bureau. Schizophrenic who live in community and half-way houses were invited. Personal interview for clinical information were performed. All patients receive anthropometric measurements and fasting blood sampling to evaluate metabolic disease status. Prevalence of metabolic diseases among our patients was described. Multiple logistic regression model was use to define the metabolic family histories risk on various metabolic outcomes.
Results:
Totally 307 patients were included in this study. Our analysis revealed prevalence in these patients were 60% for overweight, 30% for obese, 33.01% for metabolic syndrome, 33.66% for hypertension, 10.46% for diabetes mellitus and 9.48% in hypercholesterolemia. Most of these prevalence rates were higher than general population. Males tend to have hypertension. Females were found to have more diabetes and central obesity. Antipsychotics effects on metabolic diseases were not significant distinct in our study. Family history of DM elevated the risk to 2.35 in overweight, 2.01 in obesity, 2.07 in central obesity and 3.31 in DM. In addition, family history of DM increases 4.95 kg of mean body weight and 2.11 of body mass index. Family history of DM could be a predictor for overweight, obesity, central obesity and DM when patient receiving antipsychotics and as a reference for medical decision. Also, our study found interaction between antipsychotics and family history of DM , comparing to those without family history of DM, typical and second-generation antipsychotics generated more prominent risks for central obesity. Other metabolic disease family histories didn’t showed significant correlation with the metabolic outcomes in schizophrenic patients receiving antipsychotics. There are several limitations of this study. First of all, only current drug information was available. Second, there are many kinds of drugs in this study and the sample size for single drug is too small to clarify the specific drug effect. Also, information about family history was self-reported .It may be under estimated due to impaired cognitive function of schizophrenic patients.
Conclusion:
The prevalence of metabolic diseases for schizophrenic patients in community was higher than the general population. Specific gender differences were found. Family history of DM predicts overweight, obesity, central obesity and DM in schizophrenic patient with antipsychotics treatments.

並列關鍵字

schizophrenia ； antipsychotics ； obesity ； diabetes mellitus ； metabolic syndrome ； risk factor ； family history

參考文獻

2. Frankenburg, F.R., et al., Clozapine and body mass change. Biol Psychiatry, 1998. 43(7): p. 520-4.

3. Tighe, S. and T. Dinan, An overview of the central control of weight regulation and the effect of antipsychotic medication. J Psychopharmacol, 2005. 19(6 Suppl): p. 36-46.

4. Banerji, M.A., et al., Relationship of visceral adipose tissue and glucose disposal is independent of sex in black NIDDM subjects. Am J Physiol, 1997. 273(2 Pt 1): p. E425-32.

5. Dixon, L., et al., Prevalence and correlates of diabetes in national schizophrenia samples. Schizophr Bull, 2000. 26(4): p. 903-12.

6. Boston, P.F., S.M. Dursun, and M.A. Reveley, Cholesterol and mental disorder. Br J Psychiatry, 1996. 169(6): p. 682-9.