Atypical Antipsychotics and Metabolic Syndrome: From Molecular Mechanisms to Clinical Differences
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...
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doaj-9442c4c34592437ab33ece28578fb2832021-03-09T00:04:32ZengMDPI AGPharmaceuticals1424-82472021-03-011423823810.3390/ph14030238Atypical Antipsychotics and Metabolic Syndrome: From Molecular Mechanisms to Clinical DifferencesMarco Carli0Shivakumar Kolachalam1Biancamaria Longoni2Anna Pintaudi3Marco Baldini4Stefano Aringhieri5Irene Fasciani6Paolo Annibale7Roberto Maggio8Marco Scarselli9Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, ItalyDepartment of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, ItalyDepartment of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, ItalyDepartment of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, ItalyDepartment of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, ItalyDepartment of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, ItalyDepartment of Biotechnological and Applied Clinical Sciences, University of l’Aquila, 67100 L’Aquila, ItalyMax Delbrück Center for Molecular Medicine, 13125 Berlin, GermanyDepartment of Biotechnological and Applied Clinical Sciences, University of l’Aquila, 67100 L’Aquila, ItalyDepartment of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, ItalyAtypical 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.https://www.mdpi.com/1424-8247/14/3/238atypical antipsychotics (AAPs)G protein-coupled receptors (GPCRs)metabolic syndrome (MetS)weight gaintype 2 diabetesdyslipidemia |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Marco Carli Shivakumar Kolachalam Biancamaria Longoni Anna Pintaudi Marco Baldini Stefano Aringhieri Irene Fasciani Paolo Annibale Roberto Maggio Marco Scarselli |
spellingShingle |
Marco Carli Shivakumar Kolachalam Biancamaria Longoni Anna Pintaudi Marco Baldini Stefano Aringhieri Irene Fasciani Paolo Annibale Roberto Maggio Marco Scarselli Atypical Antipsychotics and Metabolic Syndrome: From Molecular Mechanisms to Clinical Differences Pharmaceuticals atypical antipsychotics (AAPs) G protein-coupled receptors (GPCRs) metabolic syndrome (MetS) weight gain type 2 diabetes dyslipidemia |
author_facet |
Marco Carli Shivakumar Kolachalam Biancamaria Longoni Anna Pintaudi Marco Baldini Stefano Aringhieri Irene Fasciani Paolo Annibale Roberto Maggio Marco Scarselli |
author_sort |
Marco Carli |
title |
Atypical Antipsychotics and Metabolic Syndrome: From Molecular Mechanisms to Clinical Differences |
title_short |
Atypical Antipsychotics and Metabolic Syndrome: From Molecular Mechanisms to Clinical Differences |
title_full |
Atypical Antipsychotics and Metabolic Syndrome: From Molecular Mechanisms to Clinical Differences |
title_fullStr |
Atypical Antipsychotics and Metabolic Syndrome: From Molecular Mechanisms to Clinical Differences |
title_full_unstemmed |
Atypical Antipsychotics and Metabolic Syndrome: From Molecular Mechanisms to Clinical Differences |
title_sort |
atypical antipsychotics and metabolic syndrome: from molecular mechanisms to clinical differences |
publisher |
MDPI AG |
series |
Pharmaceuticals |
issn |
1424-8247 |
publishDate |
2021-03-01 |
description |
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. |
topic |
atypical antipsychotics (AAPs) G protein-coupled receptors (GPCRs) metabolic syndrome (MetS) weight gain type 2 diabetes dyslipidemia |
url |
https://www.mdpi.com/1424-8247/14/3/238 |
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