Metabolic and cardiovascular adverse effects associated with antipsychotic drugs.

De Hert, Marc; Detraux, Johan; van Winkel, Ruud; Yu, Weiping; Correll, Christoph U.

doi:10.1038/nrendo.2011.156

Cited by 1,145Schizophrenia research and treatmentPharmacology and Obesity TreatmentHIV-related health complications and treatments

Metabolic and cardiovascular adverse effects associated with antipsychotic drugs.

De Hert, Marc, Detraux, Johan, van Winkel, Ruud, Yu, Weiping, Correll, Christoph U.·2012·Nature Reviews Endocrinology

DOI 10.1038/nrendo.2011.156

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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.

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Both antipsychotic and antidepressant medications are associated with numerous adverse side effects ranging from common less severe symptoms like headaches or nausea to less common but more severe symptoms like cardiovascular or metabolic dysfunction.
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Metabolic Syndrome Associated with Schizophrenia and Atypical Antipsychotics
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The incidence of diabetes in atypical antipsychotic users differs according to agent—results from a multisite epidemiologic study
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How can antipsychotics cause diabetes mellitus? Insights based on receptor-binding profiles, humoral factors and transporter proteins
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MTHFR and risk of metabolic syndrome in patients with schizophrenia
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Self-citation
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Increased Prevalence of Obesity and Glucose Intolerance in Youth Treated with Second—Generation Antipsychotic Medications
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Atypical Antipsychotic Drugs and Diabetes Mellitus in the US Food and Drug Administration Adverse Event Database: A Systematic Bayesian Signal Detection Analysis
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Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis
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Self-citation
Schizophrenia
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Mortality in people with schizophrenia: a systematic review and meta‐analysis of relative risk and aggravating or attenuating factors
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Diabetes mellitus in people with schizophrenia, bipolar disorder and major depressive disorder: a systematic review and large scale meta‐analysis
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Almost All Antipsychotics Result in Weight Gain: A Meta-Analysis
Bak, M., Fransen, A., Janssen, J., van Os, J., & Drukker, M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0094112 · Cited by 490 · see citing works
“Indeed some reviews address this issue although restricted to only schizophrenia and bipolar disorder [27,61].”
Background
Metabolic Syndrome and Metabolic Abnormalities in Bipolar Disorder: A Meta-Analysis of Prevalence Rates and Moderators
Vancampfort, D., Vansteelandt, K., Correll, C. U., Mitchell, A. J., Herdt, A. D., Sienaert, P. A., Probst, M., & Binder, M. D. (2013) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2012.12050620 · Cited by 441 · see citing works
Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review
Solmi, M., Murru, A., Pacchiarotti, I., Undurraga, J., Veronese, N., Fornaro, M., Stubbs, B., Monaco, F., Vieta, E., Seeman, M., et al. (2017) · Therapeutics and Clinical Risk Management · doi:10.2147/tcrm.s117321 · Cited by 438 · see citing works
World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Schizophrenia, Part 2: Update 2012 on the long-term treatment of schizophrenia and management of antipsychotic-induced side effects
Hasan, A., Falkai, P., Wobrock, T., Lieberman, J. A., Glenthoj, B. Y., Gattaz, W. F., Thibaut, F., Möller, H., & WFSBP Task force on Treatment Guidelines for Schizophrenia (2012) · The World Journal of Biological Psychiatry · doi:10.3109/15622975.2012.739708 · Cited by 418 · see citing works
Cardiovascular disease in patients with severe mental illness
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20‐year follow‐up study of physical morbidity and mortality in relationship to antipsychotic treatment in a nationwide cohort of 62,250 patients with schizophrenia (FIN20)
Taipale, H., Tanskanen, A., Mehtälä, J., Vattulainen, P., Correll, C. U., & Tiihonen, J. (2020) · World Psychiatry · doi:10.1002/wps.20699 · Cited by 415 · see citing works
Cardiometabolic Risk in Patients With First-Episode Schizophrenia Spectrum Disorders: Baseline Results From the RAISE-ETP Study
Correll, C. U., Robinson, D. G., Schooler, N. R., Brunette, M. F., Mueser, K. T., Rosenheck, R. A., Marcy, P., Addington, J., Estroff, S. E., Robinson, J., et al. (2014) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2014.1314 · Cited by 384 · see citing works
The WPA-Lancet psychiatry commission on the future of psychiatry
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Antipsychotic-associated weight gain: management strategies and impact on treatment adherence
Dayabandara, M., Hanwella, R., Ratnatunga, S. S., Seneviratne, S., Suraweera, C. U., & de Silva, V. A. (2017) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s113099 · Cited by 377 · see citing works
Efficacy and safety of individual second-generation vs. first-generation antipsychotics in first-episode psychosis: a systematic review and meta-analysis
Zhang, J., Gallego, J. A., Robinson, D. G., Malhotra, A. K., Kane, J. M., & Correll, C. U. (2012) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145712001277 · Cited by 336 · see citing works
Is the Prevalence of Metabolic Syndrome and Metabolic Abnormalities Increased in Early Schizophrenia? A Comparative Meta-Analysis of First Episode, Untreated and Treated Patients
Mitchell, A. J., Vancampfort, D., Herdt, A. D., Yu, W., & Hert, M. D. (2012) · Schizophrenia Bulletin · doi:10.1093/schbul/sbs082 · Cited by 331 · see citing works
What is the risk‐benefit ratio of long‐term antipsychotic treatment in people with schizophrenia?
Correll, C. U., Rubio, J. M., & Kane, J. M. (2018) · World Psychiatry · doi:10.1002/wps.20516 · Cited by 324 · see citing works
A multicenter, randomized, double-blind, controlled phase 3 trial of fixed-dose brexpiprazole for the treatment of adults with acute schizophrenia
Kane, J. M., Skuban, A., Ouyang, J., Hobart, M., Pfister, S., McQuade, R. D., Nyilas, M., Carson, W. H., Sanchez, R., & Eriksson, H. (2015) · Schizophrenia Research · doi:10.1016/j.schres.2015.01.038 · Cited by 325 · see citing works
Metabolic syndrome and metabolic abnormalities in patients with major depressive disorder: a meta-analysis of prevalences and moderating variables
Vancampfort, D., Correll, C. U., Wampers, M., Sienaert, P., Mitchell, A. J., De Herdt, A., Probst, M., Scheewe, T. W., & De Hert, M. (2014) · Psychological Medicine · doi:10.1017/s0033291713002778 · Cited by 317 · see citing works
A meta-analysis of cardio-metabolic abnormalities in drug naïve, first-episode and multi-episode patients with schizophrenia versus general population controls
Vancampfort, D., Wampers, M., Mitchell, A. J., Correll, C. U., Herdt, A. D., Probst, M., & Binder, M. D. (2013) · World Psychiatry · doi:10.1002/wps.20069 · Cited by 320 · see citing works
Association With Hospitalization and All-Cause Discontinuation Among Patients With Schizophrenia on Clozapine vs Other Oral Second-Generation Antipsychotics
Masuda, T., Misawa, F., Takase, M., Kane, J. M., & Correll, C. U. (2019) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2019.1702 · Cited by 321 · see citing works
High fat diet produces brain insulin resistance, synaptodendritic abnormalities and altered behavior in mice
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Dose-response meta-analysis of antipsychotic drugs for acute schizophrenia
Leucht, S., Crippa, A., Siafis, S., Patel, M. X., Orsini, N., & Davis, J. M. (2020) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2019.19010034 · Cited by 301 · see citing works
Efficacy and Safety of Lumateperone for Treatment of Schizophrenia
Correll, C. U., Davis, R. E., Weingart, M., Saillard, J., O’Gorman, C., Kane, J. M., Lieberman, J. A., Tamminga, C. A., Mates, S. L., & Vanover, K. E. (2020) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2019.4379 · Cited by 289 · see citing works
Weight gain and obesity in schizophrenia: epidemiology, pathobiology, and management
Manu, P., Dima, L., Shulman, M., Vancampfort, D., Hert, M. D., & Correll, C. (2015) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.12445 · Cited by 281 · see citing works
ITI-007 for the Treatment of Schizophrenia: A 4-Week Randomized, Double-Blind, Controlled Trial
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Authors: De Hert, M., Detraux, J., van Winkel, R., Yu, W., & Correll, C. U.
Affiliations: KU Leuven (BE)
Zucker Hillside Hospital (US)
ORCID: Detraux, Johan
Correll, Christoph U.
Venue: Nature Reviews Endocrinology
Publisher: Springer Science and Business Media LLC
Published: 2011-10-18
Volume: 8
Issue: 2
Pages: 114-126
ISSN: 1759-5029 (ISSN-L)
1759-5037
DOI: 10.1038/nrendo.2011.156
OpenAlex: W2014026290
Cited by: 1,145
References: 131
Citations by year: 2026: 85 · 2025: 75 · 2024: 62 · 2023: 91 · 2022: 97 · 2021: 99 · 2020: 84 · 2019: 77 · 2018: 73 · 2017: 85 · 2016: 74 · 2015: 75 · 2014: 65 · 2013: 52 · 2012: 44
FWCI: 6.96
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Reviews Endocrinology (publishedVersion)
PubMed (publishedVersion)
Research Publications (Maastricht University) (submittedVersion)
Lirias (KU Leuven) (submittedVersion)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
Health Sciences › Medicine › Emergency Medicine › HIV-related health complications and treatments
Keywords: antipsychotic drugs, type 2 diabetes, cardiovascular disease, metabolic side effects, obesity, hyperglycemia, dyslipidemia, metabolic syndrome, QT prolongation, sudden cardiac death, glucose metabolism, lipid metabolism, health care disparities, screening and monitoring
MeSH terms: Adult, Cardiovascular Diseases, Child, Diabetes Mellitus, Humans, Metabolic Diseases, Antipsychotic Agents, Weight Gain, Death, Sudden, Cardiac

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Metabolic and cardiovascular adverse effects associated with antipsychotic drugs.

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Integrity signals

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