Engl Julia, Tschoner Alexander, Laimer Markus, Rettenbacher Maria, Wolfgang Fleischhacker W, Patsch Josef R, Ebenbichler Christoph
Klinische Abteilung für Allgemeine Innere Medizin, Universitätsklinik für Innere Medizin, Medizinische Universität Innsbruck, Innsbruck, Austria.
Wien Klin Wochenschr. 2006 May;118(7-8):196-206. doi: 10.1007/s00508-006-0584-3.
Antipsychotic medications are a mainstay in the treatment of schizophrenia and are widely used in other psychiatric conditions. New generation antipsychotic agents (NGAs) are increasingly replacing first generation antipsychotic agents (FGAs), mainly due to a decreased risk for extrapyramidal symptoms, better overall tolerability, as well as some efficacy advantages. However, some of these NGAs are associated with adverse metabolic effects such as substantial weight gain, the induction of insulin resistance and lipid disorders. Among these substances, clozapine and olanzapine induce the most significant weight gain, olanzapine mainly by increasing body fat and both of these antipsychotics have been associated with disturbances in glucose metabolism. Diabetes mellitus induced by treatment with some NGAs occurred in many cases within days to weeks after initiation of SGA therapy, in some cases hyperglycemia promptly resolved after discontinuation of the medication and several reports have documented recurrent hyperglycemia after a rechallenge with the same drug. One possible pathomechanism for hyperglycemia induced by these NGAs is the induction of insulin resistance via humoral and/or cellular pathways. Alternatively, NGA induced diabetes may occur because of weight gain or a change in body fat distribution with a shift to a predominantly visceral fat type or through a direct effect on insulin sensitive target tissues. In this article we like to review the metabolic side effects of NGA treatment, highlight recent advances in the pathogenesis of these metabolic complications and discuss potential treatments of these side effects.
抗精神病药物是治疗精神分裂症的主要药物，并广泛应用于其他精神疾病。新一代抗精神病药物（NGAs）正越来越多地取代第一代抗精神病药物（FGAs），主要是因为锥体外系症状风险降低、总体耐受性更好以及一些疗效优势。然而，其中一些NGAs与不良代谢效应有关，如显著体重增加、胰岛素抵抗诱导和脂质紊乱。在这些药物中，氯氮平和奥氮平导致的体重增加最为显著，奥氮平主要通过增加体脂，并且这两种抗精神病药物都与葡萄糖代谢紊乱有关。一些NGAs治疗引起的糖尿病在开始使用第二代抗精神病药物（SGA）治疗后的数天至数周内发生在许多病例中，在某些情况下，停药后高血糖迅速缓解，并且有几份报告记录了再次使用同一药物后复发性高血糖。这些NGAs诱导高血糖的一种可能发病机制是通过体液和/或细胞途径诱导胰岛素抵抗。或者，NGAs诱导的糖尿病可能是由于体重增加或体脂分布改变，转变为主要是内脏脂肪类型，或通过对胰岛素敏感靶组织的直接作用。在本文中，我们希望回顾NGAs治疗的代谢副作用，突出这些代谢并发症发病机制的最新进展，并讨论这些副作用的潜在治疗方法。
