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...

Full description

Bibliographic Details
Main Authors: Marco Carli, Shivakumar Kolachalam, Biancamaria Longoni, Anna Pintaudi, Marco Baldini, Stefano Aringhieri, Irene Fasciani, Paolo Annibale, Roberto Maggio, Marco Scarselli
Format: Article
Language:English
Published: MDPI AG 2021-03-01
Series:Pharmaceuticals
Subjects:
Online Access:https://www.mdpi.com/1424-8247/14/3/238
id doaj-9442c4c34592437ab33ece28578fb283
record_format Article
spelling 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
work_keys_str_mv AT marcocarli atypicalantipsychoticsandmetabolicsyndromefrommolecularmechanismstoclinicaldifferences
AT shivakumarkolachalam atypicalantipsychoticsandmetabolicsyndromefrommolecularmechanismstoclinicaldifferences
AT biancamarialongoni atypicalantipsychoticsandmetabolicsyndromefrommolecularmechanismstoclinicaldifferences
AT annapintaudi atypicalantipsychoticsandmetabolicsyndromefrommolecularmechanismstoclinicaldifferences
AT marcobaldini atypicalantipsychoticsandmetabolicsyndromefrommolecularmechanismstoclinicaldifferences
AT stefanoaringhieri atypicalantipsychoticsandmetabolicsyndromefrommolecularmechanismstoclinicaldifferences
AT irenefasciani atypicalantipsychoticsandmetabolicsyndromefrommolecularmechanismstoclinicaldifferences
AT paoloannibale atypicalantipsychoticsandmetabolicsyndromefrommolecularmechanismstoclinicaldifferences
AT robertomaggio atypicalantipsychoticsandmetabolicsyndromefrommolecularmechanismstoclinicaldifferences
AT marcoscarselli atypicalantipsychoticsandmetabolicsyndromefrommolecularmechanismstoclinicaldifferences
_version_ 1724228366032175104