Helmholtz Gemeinschaft


Atypical antipsychotics and metabolic syndrome: from molecular mechanisms to clinical differences

PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader

Item Type:Review
Title:Atypical antipsychotics and metabolic syndrome: from molecular mechanisms to clinical differences
Creators Name:Carli, M. and Kolachalam, S. and Longoni, B. and Pintaudi, A. and Baldini, M. and Aringhieri, S. and Fasciani, I. and Annibale, P. and Maggio, R. and Scarselli, M.
Abstract: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.
Keywords:Atypical Antipsychotics (AAPs), G Protein-Coupled Receptors (GPCRs), Metabolic Syndrome (MetS), Weight Gain, Type 2 Diabetes, Dyslipidemia, Clozapine, Olanzapine, Animals, Mice, Rats
Page Range:238
Date:March 2021
Official Publication:https://doi.org/10.3390/ph14030238
PubMed:View item in PubMed

Repository Staff Only: item control page


Downloads per month over past year

Open Access
MDC Library