Atypical Antipsychotics and Metabolic Syndrome: From Molecular Mechanisms to Clinical Differences.
Atypical Antipsychotics and Metabolic Syndrome: From Molecular Mechanisms to Clinical Differences.
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DOI：
10.3390/ph14030238
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发表时间：
2021-03-08
期刊：
影响因子：
--
通讯作者：
Scarselli M
中科院分区：
文献类型：
--
作者：
Carli M;Kolachalam S;Longoni B;Pintaudi A;Baldini M;Aringhieri S;Fasciani I;Annibale P;Maggio R;Scarselli M
非典型抗精神病药（AAPs）是治疗精神分裂症、双相情感障碍和其他精神障碍的常用处方药。然而，它们可能会导致代谢综合征（MetS），如体重增加、血脂异常、2型糖尿病（T2D）和高血压，这些都是导致预期寿命缩短和依从性差的原因。重要的是，有明确的证据表明，早期代谢紊乱可能先于体重增加，即使后者仍然是使用AAPs的标志。事实上，AAPs严重干扰葡萄糖和脂质稳态，主要作用于下丘脑、肝脏、胰腺β细胞、脂肪组织和骨骼肌。它们通过多巴胺、血清素、乙酰胆碱和组胺受体作用于下丘脑中枢，影响神经肽和5′amp活化的蛋白激酶（AMPK）活性，从而产生生理上的交感神经外流，增加胰高血糖素水平和肝葡萄糖生成。此外，胰岛素分泌改变、血脂异常、肝脏及脂肪组织脂肪沉积、胰岛素抵抗等也成为MetS的加重因素。在临床实践中，在aap中，奥氮平和氯氮平与met的最高风险相关，而喹硫平、利培酮、阿塞平和氨硫pride引起中度改变。新的aap如齐拉西酮、鲁拉西酮和部分激动剂阿立哌唑在代谢谱上似乎更耐受。然而，这些方面必须与AAPs之间的疗效差异一起考虑，其中氯氮平仍然是最有效的。有趣的是，AAP较高的临床疗效与代谢改变风险增加之间似乎存在相关性。最后，建议将心理教育和治疗药物监测（TDM）相结合的多学科方法作为避免MetS的一线策略。此外，还讨论了药物治疗。
Atypical antipsychotics (AAPs) are commonly prescribed medications to treat schizophrenia, bipolar disorders and other psychotic disorders. However, they might cause metabolic syndrome (MetS) in terms of weight gain, dyslipidemia, type 2 diabetes (T2D), and high blood pressure, which are responsible for reduced life expectancy and poor adherence. Importantly, there is clear evidence that early metabolic disturbances can precede weight gain, even if the latter still remains the hallmark of AAPs use. In fact, AAPs interfere profoundly with glucose and lipid homeostasis acting mostly on hypothalamus, liver, pancreatic β-cells, adipose tissue, and skeletal muscle. Their actions on hypothalamic centers via dopamine, serotonin, acetylcholine, and histamine receptors affect neuropeptides and 5′AMP-activated protein kinase (AMPK) activity, thus producing a supraphysiological sympathetic outflow augmenting levels of glucagon and hepatic glucose production. In addition, altered insulin secretion, dyslipidemia, fat deposition in the liver and adipose tissues, and insulin resistance become aggravating factors for MetS. In clinical practice, among AAPs, olanzapine and clozapine are associated with the highest risk of MetS, whereas quetiapine, risperidone, asenapine and amisulpride cause moderate alterations. The new AAPs such as ziprasidone, lurasidone and the partial agonist aripiprazole seem more tolerable on the metabolic profile. However, these aspects must be considered together with the differences among AAPs in terms of their efficacy, where clozapine still remains the most effective. Intriguingly, there seems to be a correlation between AAP’s higher clinical efficacy and increase risk of metabolic alterations. Finally, a multidisciplinary approach combining psychoeducation and therapeutic drug monitoring (TDM) is proposed as a first-line strategy to avoid the MetS. In addition, pharmacological treatments are discussed as well.
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影响因子：
5.2
作者：
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通讯作者：
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影响因子：
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作者：
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DOI：
10.1038/oby.2003.78
发表时间：
2003-04-01
期刊：
OBESITY RESEARCH
影响因子：
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