A double blind, placebo-controlled, randomized crossover study of the acute metabolic effects of olanzapine in healthy volunteers.
A double blind, placebo-controlled, randomized crossover study of the acute metabolic effects of olanzapine in healthy volunteers.
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DOI：
10.1371/journal.pone.0022662
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Lynch CJ
中科院分区：
文献类型：
--
作者：
Albaugh VL;Singareddy R;Mauger D;Lynch CJ
非典型抗精神病药物表现出代谢副作用，包括糖尿病和肥胖。在动物模型中，不良事件之前是口服葡萄糖耐量（oGTT）的急性恶化沿着血浆游离脂肪酸（FFA）和瘦素的减少。目前还不清楚是否同样的急性效应发生在人类身上。进行了一项双盲、随机、安慰剂对照交叉试验，以检查奥氮平在健康志愿者中的潜在代谢效应。参与者包括男性（8）和女性（7）受试者[18-30岁，BMI 18.5-25]。受试者在oGTT检测前接受安慰剂或奥氮平（10 mg/天）治疗3天。主要终点包括测量血浆瘦素、口服葡萄糖耐量和血浆游离脂肪酸（FFA）。次要代谢终点包括：甘油三酯、总胆固醇、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇、心率、血压、体重和BMI。在oGTT期间，奥氮平使葡萄糖曲线下面积（AUC）增加42%（2808±474 vs. 3984±444 mg/dl·min; P =0.0105）。 奥氮平治疗后，空腹血浆瘦素和甘油三酯分别升高24%（瘦素：6.8±1.3 vs. 8.4±1.7 ng/ml; P = 0.0203）和22%（甘油三酯：88.9±10.1 vs. 108.2±11.6 mg/dl; P = 0.0170），而FFA和HDL分别下降32%（FFA：0.38±0.06 vs. 0.26±0.04 mM; P = 0.0166）和11%（54.2±4.7 vs. 48.9±4.3 mg/dl; P =0.0184）。 其他措施不变。在代谢副作用的啮齿动物模型中观察到奥氮平产生部分但非全部早期内分泌/代谢变化，这表明抗精神病药物的作用不仅限于葡萄糖代谢紊乱。未来的前瞻性临床研究应侧重于确定哪些可靠的代谢改变可能是有用的潜在筛选工具，在评估患者的易感性，体重增加和糖尿病引起的非典型抗精神病药物。ClinicalTrials.gov NCT00741026
Atypical antipsychotics exhibit metabolic side effects including diabetes mellitus and obesity. The adverse events are preceded by acute worsening of oral glucose tolerance (oGTT) along with reduced plasma free fatty acids (FFA) and leptin in animal models. It is unclear whether the same acute effects occur in humans. A double blind, randomized, placebo-controlled crossover trial was conducted to examine the potential metabolic effects of olanzapine in healthy volunteers. Participants included male (8) and female (7) subjects [18–30 years old, BMI 18.5–25]. Subjects received placebo or olanzapine (10 mg/day) for three days prior to oGTT testing. Primary endpoints included measurement of plasma leptin, oral glucose tolerance, and plasma free fatty acids (FFA). Secondary metabolic endpoints included: triglycerides, total cholesterol, high- and low-density lipoprotein cholesterol, heart rate, blood pressure, body weight and BMI. Olanzapine increased glucose Area Under the Curve (AUC) by 42% (2808±474 vs. 3984±444 mg/dl·min; P = 0.0105) during an oGTT. Fasting plasma leptin and triglycerides were elevated 24% (Leptin: 6.8±1.3 vs. 8.4±1.7 ng/ml; P = 0.0203) and 22% (Triglycerides: 88.9±10.1 vs. 108.2±11.6 mg/dl; P = 0.0170), whereas FFA and HDL declined by 32% (FFA: 0.38±0.06 vs. 0.26±0.04 mM; P = 0.0166) and 11% (54.2±4.7 vs. 48.9±4.3 mg/dl; P = 0.0184), respectively after olanzapine. Other measures were unchanged. Olanzapine exerts some but not all of the early endocrine/metabolic changes observed in rodent models of the metabolic side effects, and this suggest that antipsychotic effects are not limited to perturbations in glucose metabolism alone. Future prospective clinical studies should focus on identifying which reliable metabolic alterations might be useful as potential screening tools in assessing patient susceptibility to weight gain and diabetes caused by atypical antipsychotics. ClinicalTrials.gov NCT00741026
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