Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents.
Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents.
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DOI：
10.1001/jama.2009.1549
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发表时间：
2009-10-28
影响因子：
120.7
通讯作者：
Malhotra, Anil K.
中科院分区：
文献类型：
--
作者：
Correll, Christoph U.;Manu, Peter;Olshanskiy, Vladimir;Napolitano, Barbara;Kane, John M.;Malhotra, Anil K.
第二代抗精神病药物（SGAs）的心脏代谢作用令人担忧，但在antipsychotic-naïve和儿科患者中研究不足。研究SGAs对机体组成和代谢参数的影响，不受既往抗精神病药物暴露的影响。在2001年12月至2007年9月进行了为期三个月的非随机第二代抗精神病药物治疗的适应症、有效性和耐受性（SATIETY）队列研究。半城市，三级保健，学术住院和门诊服务在皇后区，纽约，有450万人口的集水区。505名年龄在4-19岁（平均年龄：13.9±3.6）岁，抗精神病药物暴露≤1周的青少年中，338人（66.9%）入选。其中，272例（80.5%）有≥1次基线后评估形成最终样本，205例（61.7%）完成了研究。患者有情绪谱（n=130, 47.8%）、精神分裂症谱（n=82, 30.1%）和破坏性/攻击性行为谱（n=60, 22.1%）。15名拒绝/非依从患者作为对照组。用阿立哌唑、奥氮平、喹硫平或利培酮治疗12周。身体组成（体重，身体质量指数百分位数/z分数，脂肪量，腰围），空腹血糖和脂质参数。奥氮平组体重增加19.0（95%可信区间：16.4,21.5）磅=15.2(13.2,17.2)%，喹硫平组体重增加13.5（10.9,16.0）磅=10.4(8.5,12.3)%，利培酮组体重增加11.9（10.7,13.1）磅=10.4(9.4,11.3)% (N=135)，阿立哌唑组体重增加9.9（8.2,11.5）磅=8.1(7.0,9.5)% （N=41）。对照受试者（N=15）体重变化最小：0.4（- 2.3,3.2）磅=0.7(- 1.3,2.6)%。84.4% （n=38）的奥氮平组、64.4% （n=87）的利培酮组、58.4% （n=24）的阿立哌唑组、55.6% （n=20）的喹硫平组和0%的对照组患者体重增加≥7%。使用奥氮平后，胆固醇（p< 0.001）、甘油三酯（p=0.002）、非高密度脂蛋白胆固醇（p< 0.001）、甘油三酯/高密度脂蛋白比值（p=0.002）、葡萄糖（p=0.02）、胰岛素（p=0.02）和HOMA-IR （p=0.03）显著升高。使用喹硫平后，胆固醇（p<0.05）、甘油三酯（p=0.01）、非高密度脂蛋白胆固醇（p=0.03）和甘油三酯/高密度脂蛋白比值（p=0.004）显著升高。利培酮组甘油三酯显著升高（p=0.04）。阿立哌唑组和对照组的代谢基线至终点变化无统计学意义。在奥氮平、利培酮、喹硫平和阿立哌唑组中，28.9% （n=13）、19.4% （n=26）、8.8% （n=3）、7.3% （n=3）的青少年出现了血脂异常，对照组中6.7% (n=1) (p=0.03)，而获得性胰岛素抵抗（HOMA-IR>4.39: 2.9%-17.8%）和代谢综合征（0%-6.5%）在本短期研究中相对少见。首次使用SGA与每种药物的显著体重增加有关。4种抗精神病药物的代谢变化不同。
Cardiometabolic effects of second-generation antipsychotics (SGAs) are concerning, but have been insufficiently studied in antipsychotic-naïve and pediatric patients. To study SGAs effects on body composition and metabolic parameters, unconfounded by prior antipsychotic exposure. Three-month, non-randomized Second-Generation Antipsychotic Treatment Indications, Effectiveness and Tolerability in Youth (SATIETY) cohort study, conducted 12.2001–09.2007. Semi-urban, tertiary care, academic inpatient and outpatient services in Queens, New York, with a 4.5 million people catchment area. Of 505 youth, aged 4–19 (mean age: 13.9±3.6) years with ≤1 week antipsychotic exposure, 338 (66.9%) were enrolled. Of these, 272 (80.5%) had ≥1 post-baseline assessment forming the final sample, and 205 (61.7%) completed the study. Patients had mood spectrum (n=130, 47.8%), schizophrenia spectrum (n=82, 30.1%) and disruptive/aggressive behavior spectrum disorders (n=60, 22.1%). Fifteen refusing/non-adherent patients served as a comparison group. 12-week treatment with aripiprazole, olanzapine, quetiapine or risperidone. Body composition (weight, Body Mass Index percentile/z-score, fat mass, waist circumference), and fasting glucose and lipid parameters. Weight increased by 19.0(95% Confidence Interval:16.4, 21.5)lbs=15.2(13.2, 17.2)% with olanzapine (N=45), 13.5(10.9, 16.0)lbs=10.4(8.5, 12.3)% with quetiapine (N=36), 11.9(10.7, 13.1)bs=10.4(9.4, 11.3)% with risperidone (N=135), and 9.9(8.2, 11.5)lbs=8.1(7.0, 9.5)% with aripiprazole (N=41). Comparison subjects (N=15) changed weight minimally: 0.4(−2.3, 3.2)lbs=0.7(−1.3, 2.6)%. Weight gain ≥7% occurred in 84.4% (n=38) of patients on olanzapine, 64.4% (n=87) on risperidone, 58.4% (n=24) on aripiprazole, 55.6% (n=20) on quetiapine, and 0% of comparison subjects. With olanzapine, cholesterol (p<.001), triglycerides (p=0.002), non-HDL-cholesterol (p<.001), triglyceride/HDL ratio (p=0.002), glucose (p=0.02), insulin (p=0.02), and HOMA-IR (p=0.03) increased significantly. With quetiapine, cholesterol (p<0.05), triglycerides (p=0.01), non-HDL-cholesterol (p=0.03), and triglyceride/HDL ratio (p=0.004) increased significantly. With risperidone, triglycerides (p=0.04) increased significantly. Metabolic baseline-to-endpoint changes were non-significant with aripiprazole and comparison subjects. Dyslipidemia developed in 28.9% (n=13), 19.4% (n=26), 8.8% (n=3), and 7.3% (n=3) of youth on olanzapine, risperidone, quetiapine and aripiprazole, and 6.7% (n=1) of comparison subjects (p=0.03), while acquired insulin resistance (HOMA-IR>4.39: 2.9%–17.8%) and metabolic syndrome (0%–6.5%) were relatively rare in this short-term study. First time SGA use was associated with significant weight gain with each medication. Metabolic changes varied among the 4 antipsychotics.
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