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

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Date
08/03/2021
Author
Carli, Marco
Kolachalam, Shivakumar
Longoni, Biancamaria
Pintaudi, Anna
Baldini, Marco
Aringhieri, Stefano
Fasciani, Irene
Annibale, Paolo
Maggio, Roberto
Scarselli, Marco
Keywords
Atypical antipsychotics (AAPs)
Clozapine
Dyslipidemia
G protein-coupled receptors (GPCRs)
Metabolic syndrome (MetS)
Olanzapine
Type 2 diabetes
Weight gain
RM Therapeutics. Pharmacology
Molecular Medicine
Pharmaceutical Science
Drug Discovery
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Abstract
Atypical antipsychotics (AAPs) are commonly prescribed medications to treat schizophre-nia, 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 ac-tions on hypothalamic centers via dopamine, serotonin, acetylcholine, and histamine receptors affect neuropeptides and 5′ AMP-activated protein kinase (AMPK) activity, thus producing a supra-physiological 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, olan-zapine 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, lurasi-done 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.
Citation
Carli , M , Kolachalam , S , Longoni , B , Pintaudi , A , Baldini , M , Aringhieri , S , Fasciani , I , Annibale , P , Maggio , R & Scarselli , M 2021 , ' Atypical antipsychotics and metabolic syndrome : from molecular mechanisms to clinical differences ' , Pharmaceuticals , vol. 14 , no. 3 , 238 . https://doi.org/10.3390/ph14030238
Publication
Pharmaceuticals
Status
Peer reviewed
DOI
https://doi.org/10.3390/ph14030238
ISSN
1424-8247
Type
Journal item
Rights
Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/4.0/).
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  • University of St Andrews Research
URI
http://hdl.handle.net/10023/24652

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