Abstract
Antipsychotic medications can induce cardiovascular and metabolic abnormalities (such as obesity, hyperglycemia, dyslipidemia and the metabolic syndrome) that are associated with an increased risk of type 2 diabetes mellitus and cardiovascular disease. Controversy remains about the contribution of individual antipsychotic drugs to this increased risk and whether they cause sudden cardiac death through prolongation of the corrected QT interval. Although some drug receptor-binding affinities correlate with specific cardiovascular and metabolic abnormalities, the exact pharmacological mechanisms underlying these associations remain unclear. Antipsychotic agents with prominent metabolic adverse effects might cause abnormalities in glucose and lipid metabolism via both obesity-related and obesity-unrelated molecular mechanisms. Despite existing guidelines and recommendations, many antipsychotic-drug-treated patients are not assessed for even the most easily measurable metabolic and cardiac risk factors, such as obesity and blood pressure. Subsequently, concerns have been raised over the use of these medications, especially pronounced in vulnerable pediatric patients, among whom their use has increased markedly in the past decade and seems to have especially orexigenic effects. This Review outlines the metabolic and cardiovascular risks of various antipsychotic medications in adults and children, defines the disparities in health care and finally makes recommendations for screening and monitoring of patients taking these agents.
Key Points
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Although all antipsychotic drugs can induce cardiovascular and metabolic dysfunction (especially in drug-naive, first-episode and pediatric populations), olanzapine and clozapine are most likely to cause such adverse effects
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Drug affinities for histamine, dopamine, serotonin and muscarinic receptors are closely linked to cardiovascular risk accumulation and metabolic dysfunction, but the exact underlying pharmacological mechanisms remain to be elucidated
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Abnormalities in glucose and lipid metabolism often occur via increased abdominal adiposity; however, antipsychotic drugs associated with pronounced metabolic adverse effects can also have a direct molecular effect
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Patients with a history of heart disease, arrhythmia, or syncope, or a family history of prolonged QT syndrome or early sudden cardiac death should not receive QT-prolonging antipsychotic drugs
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Monitoring cardiovascular risk is insufficient; patients' weight, blood pressure and fasting glucose and lipids should be assessed routinely, and, if possible, every patient should undergo electrocardiography before initiation of antipsychotic treatment
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Healthy diet, regular exercise and smoking cessation reduce patients' cardiovascular and metabolic risk; low-risk antipsychotic agents, adding weight-lowering medications and/or treating significant cardiovascular and metabolic abnormalities might also help
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M. De Hert and J. Detraux researched the data for the article and contributed equally to writing the article. R. van Winkel, W. Yu and C. U. Correll made substantial contribution to discussion of content and to reviewing and editing the manuscript before submission.
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M. De Hert declares that he has been a consultant for, received grant and/or research support and honoraria from, and been on the speakers' bureaus and/or advisory boards of the following companies: Astra Zeneca, Bristol-Myers Squibb, Eli Lilly, Janssen-Cilag, Lundbeck, Pfizer, Sanofi Aventis. R. van Winkel declares that he has been a consultant for Eli Lilly and received honoraria from Astra Zeneca, Eli Lilly and Janssen-Cilag. C. U. Correll declares that he has been a consultant and/or advisor for or has received honoraria and/or grants from the following companies: Actelion, AstraZeneca, Biotis, Boehringer-Ingelheim, Bristol-Myers Squibb, Cephalon, Eli Lilly, GlaxoSmithKline, Hoffmann-La Roche, IntraCellular Therapies, Lundbeck, Medicure, Merck, Novartis, Otsuka, Ortho-McNeill-Janssen Pharmaceuticals, Pfizer, Schering-Plough, Sunovion, Supernus, Takeda, Vanda. He also has received grants from the National Institute of Mental Health, the American Academy of Child and Adolescent Psychiatry and the National Alliance for Research in Schizophrenia and Depression. J. Detraux and W. Yu declare no competing interests.
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De Hert, M., Detraux, J., van Winkel, R. et al. Metabolic and cardiovascular adverse effects associated with antipsychotic drugs. Nat Rev Endocrinol 8, 114–126 (2012). https://doi.org/10.1038/nrendo.2011.156
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DOI: https://doi.org/10.1038/nrendo.2011.156
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