抗精神病药与代谢综合征

抗精神病物与代谢综合症 预防与干预的思考,中南大学湘雅二医院精神卫生研究所 赵靖平,代谢综合症: 概念,包含下述心血管疾病(CVD)危险因素的群体: 向心性肥胖 (腰围),体质量 血脂异常 甘油三酯 高密度脂蛋白（HDL-C） 血压 空腹血糖(FPG) ,代谢综合症的标准,1identify the same MetS individuals and need identical clinical management 1Grundy SM, et al. Circulation 2005, 112:2735-52.,Metformin addition to attenuate olanzapine-induced weight gain in drug-naive first-episode schizophrenia patients: a double-blind, placebo-controlled study,Introduction,Metformin is a hepatic-selective insulin sensitizer Metformin can increase tissue sensitivity to insulin and reduce in hepatic glucose output Metformin reduces weight, blood glucose, insulin and hemoglobin Alc (HbAlc) levels in obese nondiabetic adults Metformin is not metabolized and does not inhibit the metabolism of other drugs A litter study proved efficacy The purpose was to assess the efficacy of metformin in preventing olanzapine-induced weight gain,Method,首发住院患者,可以单一使用olanzapine治疗 18-50岁 40 patients were randomized to: olanzapine 15mg/day plus metformin 750mg/day,250mg/tid n=20 or olanapine 15mg/day plus placebo n=20 Medications were provided in double-blind fashion,Methods,Assessments included: body weight, body mass index (BMI), waist-hip-ratio (WHR) fasting glucose, insulin and IRI evaluated at 8 and 12 wks the proportion of patients had gained 7% of their body weight at 12 weeks,Results(1) Demographic and basic descriptive data,37 (92.7%) patients finished 12wks assessment No difference in: Age, sex, Duration of disease Weight (kg), BMI (18.5-23.9kg/m2), Waist circumference (cm) FG (3.5-6.4mmol/l), Insulin (4-16.8IU/ml), WHR (men0.91,women0.81), IRI (4),Results(2) Between-group differences in body weight gain,olanzapine plus metformin :1.902.72 kg olanzapine plus placebo :6.874.23 kg t=-2.86, df =35, P0.01 (第8, 12周的体质量两组存在显著性差异),Results(3) Between-group differences in BMI mean change,olanzapine plus metformin group: 0.540.92kg/m2 olanzapine plus placebo group: 2.26 1.12kg/m2 t=-3.06, df=35, P0.01 (第8, 12周的体质量两组存在显著性差异),Results(4) Between-group difference in percentage of weight gain (increased their initial body weight by more than 7%),olanzapine plus metformin group:N=3, 16.7% olanzapine plus placebo group: N=12, 63.16% 2=13.62, df =1, P0.001,Results(5) Changes in FG, insulin and IRI,Olanzapine+placebo group: insulin and IRI increased significantly during the 8th and 12th weeks Olanzapine+metformin group: No significant changes in insulin and IRI levels No significant changes in fasting glucose levels in the two groups Olanzapine plus metformin vs olanzapine plus placebo: Insulin: 0.81(2.95) : 6.78(3.29)* t=-9.075 p0.01 IRI: 0.22(0.66) 1.49(0.67)* t=-10.081 p0.01,Conclusions,Metformin was effective and safe in attenuating olanzapine-induced weight gain in drug-naive first-episode schizophrenia patients. Metformin improved insulin and IRI increasing reduced by olanzapine Patients displayed good adherence to this type of preventive intervention.,Efficacy of lifestyle interventions and metformin for the treatment of antipsychotic-induced weight gain: a randomized double-blind placebo- controlled comparison,Methods,128 patients were randomized to one of four 12-week individual treatments: metformin (750mg/day),n=32 placebo, n=32 LI plus metformin (750mg/day), n=32 or LI plus placebo, n=32 Medications were provided in double-blind fashion.,Enrollment criterion,ages of 18 and 45 met DSM- criteria for schizophrenia get weight gain more than 10% of their pre-drug body weight All patients were stable outpatient,exclusion,liver or renal diseases pregnant or lactating women cardiovascular diseases hypertension or diabetes mellitus specific systemic diseases conditions that limited their ability to perform the lifestyle modifications, such as arthritis, pulmonary diseases, neurological or dietary restrictions,Lifestyle interventions,Psychoeducation program was administered for all patients of LI plus mentformin and LI plus placebo groups at baseline, week4, week8 and week12 healthy weight management techniques Dietary intervention ：总热量控制在6903KJ/d以下：脂肪占30%（饱和脂肪酸7%），碳水化合物应占55%，蛋白质占15%-20%，每日摄入的胆固醇在200mg以下。纤维丰富的食物保证在15%以上。记载患者每日的进食情况，评估患者对饮食疗法的依从性。 Exercise intervention：每天持续进行至少30分钟的全身性有氧运动,All Assessments,Weight waist circumference fasting glucose insulin and IRI body mass index (BMI),Treatment completion rates（依从性）,All completion rates:79 complete,62% LI plus metformin group: 41% (n=13 of 32) metformin group:78% (n=25 of 32) LI plus placebo group:38% (n=13 of 32) placebo group:91% (n=29 of 32) ，（2例诊断糖尿病） x2(df=3) =28.933, P0.01 不能坚持12周：LI（30例） vs metformin（7例） 5例患者失访，不纳入统计分析，123例有4周以上的评估数据，满足ITT分析,Changes for all patients in weight,Changes for all patients in fasting glucose,Changes for all patients in