The Metabolic Syndrome During Atypical Antipsychotic Drug Treatment: Mechanisms and Management
The Metabolic Syndrome During Atypical Antipsychotic Drug Treatment: Mechanisms and Management
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DOI：
10.1089/met.2004.2.290
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发表时间：
2004-09-01
影响因子：
2.1
通讯作者：
Martinez, Maritza
中科院分区：
文献类型：
--
作者：
Baptista, Trino;De Mendoza, Soaira;Martinez, Maritza
肥胖、胰岛素抵抗、2型糖尿病和其他代谢综合征的发生率在一些精神病患者中明显升高。这是基因/环境相互作用的一个显著例子。考虑到基因的贡献，精神分裂症患者胰岛素抵抗的证据在前药理学时代就有报道。高胰岛素，葡萄糖和皮质醇水平在首发精神病中被观察到。2型糖尿病的频率在精神分裂症和双相情感障碍患者及其一级亲属中显著增加。最后，精神分裂症与参与糖酵解的酶之间存在联系，抗精神病药物引起的体重增加与血清素受体多态性之间存在联系。重要的环境因素是不良的饮食习惯、吸烟、缺乏体育锻炼和药物治疗，主要是抗精神病药物（apd）和情绪稳定剂。apd可能通过在易感受试者中产生突然的食欲增加和体重增加来诱导代谢功能障碍。然而，已经提出了不依赖于体重变化的药物对糖脂代谢的直接影响。体重过度增加主要见于氯氮平、奥氮平、氯丙嗪和硫氮嗪，利培酮或喹硫平的体重增加较少。最近推出的两种apd，齐拉西酮和阿立哌唑，对体重和代谢的影响是中性的。在APD治疗过程中，必须及早发现高危人群，以便提供生活方式咨询和药物帮助。apd的近期研究议程是完善药物性代谢功能障碍的动物模型；阐明体重增加和食欲刺激以外的机制；并在随机双盲研究中测试药物，以预防或逆转选定患者的代谢综合征。
The frequency of obesity, insulin resistance, type 2 diabetes mellitus and other components of metabolic syndrome appear to be significantly elevated in some psychiatric patients. This is a notable example of genetic/environment interaction. Considering the genetic contribution, evidence of insulin resistance in persons with schizophrenia was reported in the pre-pharmacological era. High insulin, glucose, and cortisol levels are observed in first episode psychosis. The frequency of type 2 diabetes mellitus is significantly increased in persons with schizophrenia and bipolar disorder and in their first-degree relatives. Finally, a link exists between schizophrenia and enzymes involved in glycolysis and between antipsychotic drug-induced weight gain and serotonin receptor polymorphism. Important environmental factors are poor dietary habits, smoking, lack of physical exercise, and drug treatment, mostly with antipsychotic drugs (APDs) and perhaps with mood stabilizers. The APDs probably induce metabolic dysfunction by producing sudden appetite increase and weight gain in predisposed subjects. However, direct drug effects on glucose and lipid metabolism independent from body weight change have been proposed. Excessive weight gain is mainly observed with clozapine, olanzapine, chlorpromazine, and thioridazine and is less consistently noted with risperidone or quetiapine. Two recently introduced APDs, ziprasidone and aripiprazole, display a neutral effect on weight and metabolism. Subjects at high risk must be identified early during APD treatment so that provide lifestyle counseling and pharmacological assistance can be provided. The immediate research agenda for the APDs is to improve the animal models of drug-induced metabolic dysfunction; to clarify mechanisms other than weight gain and appetite stimulation; and to test pharmacological agents in randomized, double-blind studies to prevent or reverse metabolic syndrome in selected patients.