氯氮平、氟哌啶醇和氯丙嗪对慢性精神分裂症患者糖、脂代谢及体质量的影响

目的 探讨氯氮平、氟哌啶醇和氯丙嗪对慢性精神分裂症患者的糖、脂代谢和体质量的影响。方法 对服用氯氮平（89例，氯氮平组），服用氟哌啶醇（87例，氟哌啶醇组）及服用氯丙嗪（83例，氯丙嗪组）治疗的慢性精神分裂症患者于治疗前后的不同时间进行血糖、胰岛素、血脂及体质量测定，并做相关因素分析。结果 氯氮平组治疗第90天和第180天空腹血糖异常（空腹血浆血糖〉7.0mmo/L）的发生率分别为8％及24％，氟哌啶醇组分别为1％和2％，氯丙嗪组分别为1％及4％。治疗第90天氯氮平组和氯丙嗪组的空腹及餐后2h血糖浓度均较治疗前升高，治疗第180天的血糖浓度高于第90天，氟哌啶醇组各时点的变化则不明显；差异均有统计学意义（P均〈0．01）。治疗第90天，氯氮平组的体质量平均高于治疗前5．5％，氯丙嗪组高于治疗前4．8％；治疗第180天两组分别高于治疗前9．1％和7．4％；氟哌啶醇组则无明显变化；三组间的差异有统计学意义（P〈0．01）。三组患者治疗第180天的胰岛素浓度均高于治疗前，差异均有统计学意义（P均〈0．01），但三组间的差异无统计学意义（P〉0．05）。氯氮平组和氯丙嗪组的胆固醇和甘油三酯浓度均高于治疗前，差异均有统计学意义（P均〈0．01），氟哌啶醇组则无明显变化。治疗第180天氯氮平组和氯丙嗪组患者血糖、胰岛素、血脂浓度与体质量均有一定相关性（r=0．23-0．39）；氯氮平组的血糖、体质量、血脂代谢还与血药浓度呈显著性相关（r=0．28-0．62），差异均有统计学意义（P〈0．05或〈0．01）。结论 氯氮平和氯丙嗪治疗影响慢性精神分裂症患者的糖、脂代谢及体质量。     

门诊精神分裂症患者服药依从性评定及血药浓度检测的意义

目的 探讨血药深度检测对评定门诊精神分裂症患者对抗精神病药依从性（以理简称依从性）的意义。方法 对７１８例单一服用氯丙嗪、奋乃静、氯氮平或氟哌啶醇的门诊精神分裂症患者说不定依从性。于入组第２周末和第３个月末分别测定患者的血药浓度，研究时间为３个月。结果 服用氯氮平或奋乃静患者的依从性好于服用氯丙嗪和氟哌啶醇者，不依从率分别为５．４％、１０．５％，１９．５％和２１．１％。服用氯丙嗪、奋乃静或氯氮平者     

氟哌啶醇与奥氮平治疗精神分裂症疗效和安全性的随机对照研究

目的比较氟哌啶醇与奥氮平治疗精神分裂症的疗效及安全性。方法将符合精神分裂症诊断标准的住院患者按照1:2比例随机分为氟哌啶醇(n=120)和奥氮平治疗组(n=252),进行为期6周的治疗观察;于基线及治疗2、4、6周末评定阳性和阴性症状量表(positive and negative syndrom scale,PANSS),锥体外系副反应量表(rating scale for extrapyramdal side effects,RSESE)、静坐不能评定量表(barnes akathisia rating scale,BARS)和异常不自主运动量表(abnormal involuntary movement scale,AIMS);计算体质量指数(body mass index,BMI);基线及治疗4、6周末测定空腹血糖、血脂和肝功能等指标。结果氟哌啶醇组与奥氮平组基线PANSS总分差异无统计学意义;第6周末氟哌啶醇组PANSS总分低于奥氮平组(53.31±1.64 vs.58.05±1.02),减分率高于后者(60.63±2.86%vs.52.45±1.80%),均P<0.05;两组有效率(66.7%vs.62.7%)差异无统计学意义。第6周末氟哌啶醇组BMI较基线的变化值(0.08±0.20 kg/m2vs.0.91±0.12 kg/m2)、谷丙转氨酶异常病例数比例(16.98%vs.28.07%)均低于奥氮平组(P<0.05);第4周末氟哌啶醇组甘油三酯较基线的变化值低于奥氮平组(0.24±0.12 mmol/L vs.0.57±0.07 mmol/L),P<0.05。氟哌啶醇组锥体外系不良反应发生率(73.3%)明显高于奥氮平组(10.71%),P<0.05。结论在精神分裂症急性期,氟哌啶醇治疗有效率与奥氮平相当,对体重、血脂、转氨酶的影响较小,但锥体外系不良反应发生率较高。     

氯氮平,氟哌啶醇对精神分裂症患者血清催乳素的影响

本文对１６例服用氯氮平、氟哌啶醇的精神分裂症患者血清催乳素（ＰＲＬ）浓度进行测定分析。结果：氟哌啶醇组的血清ＰＲＬ浓度（Ｘ↑－＝３２．９μｇ／Ｌ）与治疗前相比有明显增高；氯氮平组的ＰＲＬ浓度（Ｘ↑－＝７．０１μｇ／Ｌ）与治疗前无显著差异。提示氯氮平与氟哌啶醇对多巴胺的影响不同。     

药源性糖尿病的研究

目的 了解氯氮平与典型抗精神病药引发糖尿病的差异，探讨氯氮平引起血糖增高的相关因素。方法 对中铁五局怀化医院1999～2003年10月收治的328例精神分裂症患进行血糖变化调查，对有关资料进行分析。结果 184例服用氯氮平的患发生糖尿病17例(9．20％)；144例接受典型抗精神病药(氯丙嗪45例，奋乃静40例，舒必利53例，氟哌啶醇6例)治疗，发生糖尿病3例(2．08％)，经Logistic回归分析，提示氯氮平致糖尿病的危险因素包括：体重指数、血脂、年龄、家族史．而与用药时间、剂量、性别等无显差异性。结论 服用氯氮平与典型抗精神病药，前可显增加糖尿病发生率。对于体重指数，血脂浓度增高及年龄较大，有家族史应加强血糖、血脂的监测。     

利培酮合并氯硝西泮治疗精神分裂症急性兴奋的研究

目的 与氯氮平和氟哌啶醇相对照,观察利培酮合并氯硝西泮治疗精神分裂症急性兴奋的疗效及不良反应特点。方法 254例精神分裂症急性期中度兴奋患者,随机分为口服利培酮合并肌内注射氯硝西泮组(88例,以下简称利培酮组)、口服氯氮平组(84例,氯氮平组)和肌内注射氟哌啶醇组(82例,氟哌啶醇组)治疗,疗程均为7 d。治疗期间每日评估阳性和阴性症状量表(PANSS)兴奋因子(PANSS-EC)和治疗中需处理的不良反应量表。结果 利培酮组的疗效与氯氮平组、氟哌啶醇组比较,经重复测量分析显示PANSS-EC分,差异无显著性(F=1.65,P=0.194)。3组精神分裂症患者的急性兴奋症状均获明显改善(各组组内治疗前后比较,F=415.35,P<0.01)。氟哌啶醇组锥体外系副反应发生率高于利培酮组和氯氮平组(P<0.01);氯氮平组嗜睡、便秘、流涎和心动过速的发生率高于利培酮组和氟哌啶醇组(P<0.05-0.01)。结论 利培酮合并氯硝西泮可有效治疗精神分裂症急性期中度兴奋患者,疗效与氯氮平和氟哌啶醇的疗效相当;安全性优于氯氮平和氟哌啶醇。     

利培酮、氯氮平和氟哌啶醇治疗精神分裂症的疗效比较结果

目的　比较利培酮、氯氮平和氟哌啶醇的疗效和不良反应。方法　将符合CCMD - 2 -R诊断标准的精神分裂症患者 ,根据入院顺序分别进入利培酮组、氯氮平组和氟哌啶醇组 ,并观察 8周。以PANSS和TESS量表评定药物的疗效和不良反应。结果　利培酮组、氯氮平组和氟哌啶醇组的PANSS量表总分、阴性分量表、一般精神病理学分量表评分均下降 ;利培酮组和氯氮平组减分较氟哌啶醇组明显 (分别P <0 0 1,P <0 0 5 ) ,TESS量表的评分也与氟哌啶醇组有显著性差异 (分别P <0 0 1,P <0 0 5 ) ;利培酮组、氯氮平组和氟哌啶醇组肝功能、心电图检查结果 ,组间差异有非常显著意义 (P <0 0 1) ;利培酮组不良反应少于氯氮平组和氟哌啶醇组。结论　利培酮、氯氮平和氟哌啶醇均具有较强的抗精神病作用 ,利培酮的安全性相对较好。     

氯氮平与氟哌啶醇对血清一氧化氮含量的影响

目的：观察氯氮平与氟哌啶醇对精神分裂症患者血清一氧化氮(NO)含量的影响。方法：对122例精神分裂症患者随机分为氯氮平组和氟哌啶醇组，并分别再分为阳性症状为主(阳性组)和阴性症状为主(阴性组)。分别用氯氮平或氟哌啶醇治疗8周。治疗前和治疗第2、4、8周末分别检测血清NO含量，并观察各组之间NO动态变化。选择30名健康者为对照组。结果：治疗前血清NO含量两阳性组均显著高于正常对照组，两阴性组均显著低于正常对照组。两阳性组之间和两阴性组之间差异均无显著性；治疗后两阳性组血清NO含量均逐渐下降，到第8周末接近正常水平，与对照组相仿。而氯氮平组的阴性组逐渐上升，与治疗前比较，第4、8周末差异显著，第8周末与对照组相仿；氟哌啶醇组的阴性组逐渐上升，但与治疗前比较，到第8周末差异显著，与对照组比较差异仍显著。治疗后两阳性组差异无显著性；两阴性组，第2、4周末差异无显著性，第8周末有显著差异。结论：氯氮平和氟哌啶醇对精神分裂症患者血清NO含量有影响，阳性症状为主患者的血清NO含量降低，阴性症状为主患者血清NO含量升高，且氯氮平升高以阴性症状为主患者血清NO含量的作用较氟哌啶醇更为明显。     

氯氮平与利培酮对精神分裂症患者血糖的影响

目的　探讨氯氮平与利培酮对精神分裂症患者血糖的影响。方法　对 6 0例精神分裂症患者分为氯氮平组和利培酮组 ,进行为期 8周的治疗 ,采用自身对照 ,比较用药前后血糖浓度。结果　氯氮平组治疗后血糖浓度显著升高 (P <0 .0 5 ) ;利培酮组治疗后血糖无明显变化 (P >0 .0 5 )。结论　氯氮平可引起精神分裂症患者血糖升高 ;利培酮则无明显影响     

奥氮平与氟哌啶醇治疗女性精神分裂症患者的对照研究

目的比较奥氮平与氟哌啶醇治疗女性精神分裂症患者的疗效及安全性。方法将符合条件的100例住院女性精神分裂症患者随机分为奥氮平组和氟哌啶醇组,共治疗3个月,采用PANSS、TESS、健康状况问卷（SF-36）进行疗效、不良反应和生活质量评估,同时检测血清泌乳素水平。结果两组治疗前后PANSS评分均有显著性差异（P〈0．01）,治疗结束后阴性症状评分奥氮平组明显低于氟哌啶醇组,有显著差异（P〈0．01）;奥氮平组在生理机能、生理职能、生命活力、社会功能、情感职能5个因子分及生活质量总评分均明显高于氟哌啶醇组（P〈0．05）;治疗结束后奥氮平组泌乳素水平显著低于氟哌啶醇组（P〈0．01）。结论奥氮平治疗女性精神分裂症疗效好,安全性高,生活质量优于氟哌啶醇。     

四种抗精神病药对糖代谢及脂代谢的不良影响

目的研究4种抗精神病药对糖代谢、脂代谢的不良影响。方法112例精神分裂症患者根据临床治疗需要分为氯氮平组（30例）、奥氮平组（24例）、利培酮组（29例）和舒必利组（29例），均治疗观察4周。每组患者于治疗前后测空腹血糖、甘油三酯、胆固醇、胰岛素、C肽，量身高、体质量、腰围、臀围，并计算体质量指数（BMI）及胰岛素抵抗指数（IR）。结果（1）治疗后4组患者的空腹胰岛素、C肽及IR均升高，与治疗前的差异有统计学意义（P〈0．05）；治疗后氯氮平组和奥氮平组患者的甘油三酯及胆固醇均明显高于治疗前（P〈0．05）。（2）治疗后BMI的升高程度为：氯氮平〉奥氮平〉舒必利〉利培酮，差异均有统计学意义（P〈0．05）。空腹胰岛素、C肽、甘油三酯、胆固醇及IR的升高程度为：氯氮平和奥氮平〉舒必利和利培酮，差异均有统计学意义（P〈0．05）。（3）氯氮平组、奥氮平组的甘油三酯及IR升高程度均为男性大于女性，胆固醇升高程度为女性大于男性；舒必利组的变化则相反。结论氯氮平和奥氮平对糖代谢及脂代谢的影响大于利培酮和舒必利，并存在性别差异。     

Serum glucose and lipid changes during the course of clozapine treatment: the effect of concurrent beta-adrenergic antagonist treatment

We examined the effects of long-term clozapine treatment, concurrent treatment with beta-adrenergic antagonists, and clozapine-induced weight gain on serum glucose and lipid measures. Fifty subjects met the DSM-III-R criteria for schizophrenia or schizoaffective disorder, participated in a 10-week, double-blind comparison of haloperidol and clozapine and a 1-year, open-label clozapine trial, and had available serum glucose and lipid levels. Weight and glucose, and lipid laboratory values were measured at the baseline and throughout the double-blind and year-long study. There were significant increases in serum triglyceride, total cholesterol, and glucose levels during the course of clozapine treatment. There were no significant changes in high-density lipoprotein (HDL) or low-density lipoprotein (LDL). Propranolol and atenolol had additive effects on changes in the total cholesterol and triglycerides, with propranolol having the most pronounced effects. Propranolol and atenolol had no significant effect on the serum glucose levels. There were significant correlations between the triglyceride and HDL level changes and clozapine-associated weight gain during the study. There were no significant correlations between the change in serum total cholesterol, LDL, or glucose and weight gain. Clozapine therapy has adverse effects on glucose and lipid homeostasis, with clozapine-induced changes in serum glucose likely due to the inherent pharmacological properties of clozapine. Concurrent beta-adrenergic receptor antagonist treatment may have an additive effect on serum lipids, and clozapine-associated weight gain also plays a modest role in triglyceride increases.     

氯氮平对精神分裂症患者体质量、血脂及胰岛素抵抗的影响

目的:探讨氯氮平对精神分裂症患者体质量(体重)、血脂及胰岛素抵抗的影响。方法:28例氯氮平治疗的精神分裂症住院患者,其中26例完成研究,分别在治疗前和治疗6周末评定阳性与阴性症状量表(PANSS),测量体质量、身高、血糖、血脂、胰岛素及氯氮平药物浓度。结果:与治疗前比较,氯氮平治疗前后体质量指数、三酰甘油水平的增加差异均有显著性(t=-3.181,P=0.004;t=-3.822,P=0.001)。血糖、胆固醇、胰岛素以及胰岛素抵抗等的变化与氯氮平血药物浓度有关。结论:氯氮平可影响精神分裂症患者的体质量指数和血脂水平,氯氮平浓度与胰岛素抵抗有关。     

Clozapine-associated elevation in serum triglycerides.

OBJECTIVE: This study was conducted to determine serum lipid level changes in patients who received clozapine or haloperidol. METHOD: Medical records of 222 inpatients treated with clozapine or haloperidol were reviewed. Age, weight, gender, daily antipsychotic dose, total cholesterol level, serum triglyceride level, and concurrent medications were recorded. RESULTS: Clozapine-treated men had significantly higher follow-up serum triglyceride concentrations over baseline than did haloperidol-treated men. Female patients experienced serum triglyceride level elevations regardless of antipsychotic treatment. Changes in total cholesterol levels were not significantly different between treatment groups. CONCLUSIONS: An increase in serum triglyceride levels occurred in clozapine-treated patients; screening for serum triglyceride elevations may be warranted before treatment with clozapine.     

氯氮平与利培酮对血清脂联素的影响

目的：研究氯氮平与利培酮对血清脂联素（Adi）等代谢的影响。方法：69例精神分裂症患者随机分为氯氮平组和利培酮组。治疗6周测定患者血清Adi,血脂,空腹血糖、胰岛素水平,计算胰岛素抵抗指数（IR）,测量身高、体质量,计算体质量指数（BMI）,并与36名正常对照者比较。结果：两患者组治疗后的血清Adi明显降低,氯氮平组血清Adi改变与BMI相关;利培酮组血清Adi改变与IR和利培酮剂量相关。结论：氯氮平与利培酮治疗精神分裂症患者可引起血清Adi降低,并与体质量增加、IR、血脂及利培酮剂量密切相关。     

Adjunctive fluvoxamine inhibits clozapine-related weight gain and metabolic disturbances

BACKGROUND: Adjunctive fluvoxamine inhibits clozapine metabolism and decreases plasma norclozapine (a toxic metabolite of clozapine) to clozapine ratios. This study aimed to demonstrate the effects of fluvoxamine on clozapine-related weight gain, hyperglycemia, and lipid abnormalities. METHOD: Sixty-eight treatment-resistant inpatients with a DSM-IV diagnosis of schizophrenia were randomly assigned to 2 treatment groups for 12 weeks. The monotherapy group (N = 34) received clozapine (< or = 600 mg/day). The coadministration group (N = 34) received fluvoxamine (50 mg/day) plus low-dose clozapine (< or = 250 mg/day). The study was conducted from August 1999 to October 2002. RESULTS: The 2 groups were similar in demographic data; baseline body weight and body mass index (BMI); baseline serum glucose, triglyceride, and cholesterol levels; and steady-state plasma clozapine concentration. The monotherapy patients (but not the coadministration patients) had significantly higher (p < .05) body weight, BMI, and serum glucose and triglyceride levels after treatment than at baseline. At week 12, the monotherapy patients also had significantly higher glucose (p = .035), triglyceride (p = .041), and norclozapine (p = .009) (and numerically higher cholesterol) levels than the cotreatment patients. The changes in weight and serum glucose and triglyceride levels were significantly correlated (p = .026, p = .005, and p = .028, respectively) with the plasma concentration of norclozapine but not with plasma levels of clozapine. CONCLUSION: These results suggest that fluvoxamine cotreatment can attenuate weight gain and metabolic disturbances in clozapine-treated patients. Plasma levels of norclozapine, but not clozapine, are associated with increases in weight and serum glucose and triglyceride levels. Of note, coadministration of fluvoxamine could increase plasma clozapine levels markedly and carry the risk of adverse events. If this combined treatment is applied, conservative introduction with reduced clozapine dosage and careful therapeutic drug monitoring of clozapine concentration is recommended.     

The effects of novel antipsychotics on glucose and lipid levels

BACKGROUND: The novel antipsychotics are extensively used based on their favorable extrapyramidal side effect profiles. However, accumulating evidence suggests that these agents, particularly clozapine and olanzapine, have serious side effects of their own, including weight gain and elevated glucose and triglyceride levels. The goal of this study is to compare the effects of novel antipsychotics clozapine, olanzapine, risperidone, and quetiapine and typical antipsychotics haloperidol and fluphenazine on glucose and lipid levels. METHOD: The charts of 590 patients were retrospectively reviewed. Of those, 215 patients had adequate laboratory data for inclusion. Glucose and lipid level data from 2 1/2 years before and after initiation of the target antipsychotic were included. Covariates, including patients' age, the duration of antipsychotic treatment, other medications that may affect glucose or lipid levels, and the initial laboratory values, were controlled for in the analyses. RESULTS: Glucose levels were increased from baseline for patients treated with clozapine, olanzapine, and haloperidol. There were statistically and clinically significant differences among the medications' effects on lipid profiles (p < .05). Those receiving clozapine and olanzapine demonstrated statistically significant increases in triglyceride levels compared with the other groups. Over one third of patients treated with any of the novel antipsychotics had clinically meaningful triglyceride elevations. CONCLUSION: It has been shown that novel antipsychotics are associated with weight gain. This risk factor along with others, such as elevated glucose and triglyceride levels, compounds the risk for coronary artery disease. Routine monitoring of glucose and lipid levels during treatment with novel antipsychotics should be advocated.     

氯氮平对超敏C反应蛋白及糖脂代谢的影响

目的：探讨氯氮平对精神分裂症患者超敏C反应蛋白（hs-CRP）以及糖、脂代谢的影响。方法：对30例服用氯氮平治疗的精神分裂症患者（患者组）作hs-CRP、空腹血糖、三酰甘油、胆固醇、高密度脂蛋白（HDL）、低密度脂蛋白（LDL）、载脂蛋白A1（ApoA1）、载脂蛋白B（ApoB）检测,于治疗前、治疗第4、8、12周各检测1次。并与30名健康者（对照组）进行比较。结果：治疗前患者组和对照组糖脂各值差异无显著性。在治疗第4、8、12周的hs-CRP,第12周的空腹血糖、三酰甘油、胆固醇、LDL、ApoB比治疗前明显升高;治疗第12周的HDL、ApoA1比治疗前明显下降;hs-CRP与空腹血糖、三酰甘油、胆固醇以及氯氮平剂量呈正相关。结论：氯氮平对hs-CRP、糖脂代谢均会产生影响,氯氮平导致代谢综合征可能与hs-CRP有关。     

Changes in glucose and cholesterol levels in patients with schizophrenia treated with typical or atypical antipsychotics

OBJECTIVE: The association of hyperglycemia and hypercholesterolemia with use of atypical antipsychotics has been documented in case reports and uncontrolled studies. The authors' goal was to assess the effects of clozapine, olanzapine, risperidone, and haloperidol on glucose and cholesterol levels in hospitalized patients with schizophrenia or schizoaffective disorder during a randomized double-blind 14-week trial. METHOD: One hundred fifty-seven patients with schizophrenia or schizoaffective disorder who were inpatients at four hospitals were originally included in the study. The 14-week trial consisted of an 8-week fixed-dose period and a 6-week variable-dose period. Planned assessments included fasting glucose and cholesterol, which were collected at baseline and at the end of the 8-week period and the following 6-week period. RESULTS: One hundred eight of the 157 patients provided blood samples at baseline and at least at one point after random assignment to clozapine, olanzapine, risperidone, or haloperidol during the treatment trial. Seven of these patients had diabetes; their glucose levels were >125 mg/dl at baseline. Data from 101 patients were used for statistical analyses. During the initial 8-week period there was an overall significant increase in mean glucose levels. There were significant increases in glucose levels at the end of the 8-week fixed-dose period for patients given clozapine (N=27) and those given haloperidol (N=25). The olanzapine group showed a significant increase of glucose levels at the end of the 6-week variable-dose period (N=22). Fourteen of the 101 patients developed abnormal glucose levels (>125 mg/dl) during the trial (six with clozapine, four with olanzapine, three with risperidone, and one with haloperidol). Cholesterol levels were increased at the end of the 8-week fixed-dose period for the patients given clozapine (N=27) and those given olanzapine (N=26); cholesterol levels were also increased at the end of the 6-week variable-dose period for patients given olanzapine (N=22). CONCLUSIONS: In this prospective randomized trial, clozapine, olanzapine, and haloperidol were associated with an increase of plasma glucose level, and clozapine and olanzapine were associated with an increase in cholesterol levels. The mean changes in glucose and cholesterol levels remained within clinically normal ranges, but approximately 14% of the patients developed abnormally high glucose levels during the course of their participation in the study.