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Metabolic and cardiovascular adverse effects associated with antipsychotic drugs

Nature Reviews Endocrinology volume 8, pages 114–126 (2012)Cite this article

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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.

Key Points

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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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References

  1. Tandon, R., Nasrallah, H. A. & Keshavan, M. S. Schizophrenia, “just the facts” 5. Treatment and prevention. Past, present, and future. Schizophr. Res. 122, 1–23 (2010).

    Article  PubMed  Google Scholar 

  2. Comer, J. S., Olfson, M. & Mojtabai, R. National trends in child and adolescent psychotropic polypharmacy in office-based practice, 1996–2007. J. Am. Acad. Child. Adolesc. Psychiatry 49, 1001–1010 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  3. De Hert, M., Dobbelaere, M., Sheridan, E. M., Cohen, D. & Correll, C. U. Metabolic and endocrine adverse effects of second-generation antipsychotics in children and adolescents: a systematic review of randomized, placebo controlled trials and guidelines for clinical practice. Eur. Psychiatry 26, 144–158 (2011).

    Article  CAS  PubMed  Google Scholar 

  4. Mojtabai, R. & Olfson, M. National trends in psychotropic medication polypharmacy in office-based psychiatry. Arch. Gen. Psychiatry 67, 26–36 (2010).

    Article  PubMed  Google Scholar 

  5. Kane, J. M. & Correll, C. U. Past and present progress in the pharmacologic treatment of schizophrenia. J. Clin. Psychiatry 79, 1115–1124 (2010).

    Article  Google Scholar 

  6. Leucht, S., Arbter, D., Engel, R. R., Kissling, W. & Davis, J. M. How effective are second-generation antipsychotic drugs? A meta-analysis of placebo-controlled trials. Mol. Psychiatry 14, 429–447 (2009).

    Article  CAS  PubMed  Google Scholar 

  7. Leucht, S. et al. A meta-analysis of head-to-head comparisons of second-generation antipsychotics in the treatment of schizophrenia. Am. J. Psychiatry 166, 152–163 (2009).

    Article  PubMed  Google Scholar 

  8. Leucht, S. et al. Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet 373, 31–41 (2009).

    Article  CAS  PubMed  Google Scholar 

  9. Rummel-Kluge, C. et al. Second-generation antipsychotic drugs and extrapyramidal side effects: a systematic review and meta-analysis of head-to-head comparisons. Schizophr. Bull. http://dx.doi.org/10.1093/schbul/sbq042.

  10. Maayan, L., Vakhrusheva, J. & Correll, C. U. Effectiveness of medications used to attenuate antipsychotic-related weight gain and metabolic abnormalities: a systematic review and meta-analysis. Neuropsychopharmacology 35, 1520–1530 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Correll, C. U., Lencz, T. & Malhotra, A. K. Antipsychotic drugs and obesity. Trends Mol. Med. 17, 97–107 (2011).

    Article  CAS  PubMed  Google Scholar 

  12. Morrato, E. H. et al. Metabolic testing rates in 3 state Medicaid programs after FDA warnings and ADA/APA recommendations for second-generation antipsychotic drugs. Arch. Gen. Psychiatry 67, 17–24 (2010).

    Article  PubMed  Google Scholar 

  13. Morrato, E. H. et al. Metabolic screening in children receiving antipsychotic drug treatment. Arch. Pediatr. Adolesc. Med. 164, 344–351 (2010).

    Article  PubMed  Google Scholar 

  14. Mitchell, A. J., Delaffon, V., Vancampfort, D., Correll, C. U. & De Hert, M. Guideline concordant monitoring of metabolic risk in people treated with antipsychotic medication: systematic review and meta-analysis of screening practices. Psychol. Med. http://dx.doi.org/10.1017/S003329171100105X.

  15. Maina, G., Salvi, V., Vitalucci, A., D'Ambrosio, V. & Bogetto, F. Prevalence and correlates of overweight in drug-naïve patients with bipolar disorder. J. Affect. Disord. 110, 149–155 (2008).

    Article  PubMed  Google Scholar 

  16. De Hert, M. et al. Physical illness in patients with severe mental disorders. I. Prevalence, impact of medications and disparities in health care. World Psychiatry 10, 52–77 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  17. van Winkel, R. et al. Psychiatric diagnosis as an independent risk factor for metabolic disturbances: results from a comprehensive, naturalistic screening program. J. Clin. Psychiatry 69, 1319–1327 (2008).

    Article  PubMed  Google Scholar 

  18. van Winkel, R. et al. Prevalence of diabetes and the metabolic syndrome in a sample of patients with bipolar disorder. Bipolar Disord. 10, 342–348 (2008).

    Article  PubMed  Google Scholar 

  19. Parsons, B. et al. Weight effects associated with antipsychotics: a comprehensive database analysis. Schizophr. Res. 110, 103–110 (2009).

    Article  PubMed  Google Scholar 

  20. Coccurello, R. & Moles, A. Potential mechanisms of atypical antipsychotic-induced metabolic derangement: clues for understanding obesity and novel drug design. Pharmacol. Ther. 127, 210–251 (2010).

    Article  CAS  PubMed  Google Scholar 

  21. Kahn, R. S. et al. Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial. Lancet 371, 1085–1097 (2008).

    Article  CAS  PubMed  Google Scholar 

  22. Newcomer, J. W. Second-generation (atypical) antipsychotics and metabolic effects: a comprehensive literature review. CNS Drugs 19 (Suppl. 1), 1–93 (2005).

    CAS  PubMed  Google Scholar 

  23. Lieberman, J. A. et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N. Engl. J. Med. 353, 1209–1223 (2005).

    Article  CAS  PubMed  Google Scholar 

  24. Citrome, L. Risk–benefit analysis of available treatments for schizophrenia. Psychiatric Times 1, 27–30 (2007).

    Google Scholar 

  25. Tarricone, I., Ferrari Gozzi, B., Serretti, A., Grieco, D. & Berardi, D. Weight gain in antipsychotic-naive patients: a review and meta-analysis. Psychol. Med. 40, 187–200 (2010).

    Article  CAS  PubMed  Google Scholar 

  26. Alvarez-Jiménez, M. et al. Antipsychotic-induced weight gain in chronic and first-episode psychotic disorders: a systematic critical reappraisal. CNS Drugs 22, 547–562 (2008).

    Article  PubMed  Google Scholar 

  27. Strassnig, M., Miewald, J., Keshavan, M. & Ganguli, R. Weight gain in newly diagnosed first-episode psychosis patients and healthy comparisons: one-year analysis. Schizophr. Res. 93, 90–98 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  28. Correll, C. U. et al. Recognizing and monitoring adverse events of second-generation antipsychotics in children and adolescents. Child. Adolesc. Psychiatr. Clin. N. Am. 15, 177–206 (2006).

    Article  PubMed  Google Scholar 

  29. Mitchell, A. J., Vancampfort, D., Sweers, K., van Winkel, R. & De Hert, M. Prevalence of metabolic syndrome and metabolic abnormalities in schizophrenia and related disorders—a PRISMA meta-analysis. Schizophr. Bull. (in press).

  30. Correll, C. U. et al. Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents. JAMA 302, 1765–1773 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Correll, C. U., Sheridan, E. M. & DelBello, M. P. Antipsychotic and mood stabilizer efficacy and tolerability in pediatric and adult patients with bipolar I mania: a comparative analysis of acute, randomized, placebo-controlled trials. Bipolar Disord. 12, 116–141 (2010).

    Article  CAS  PubMed  Google Scholar 

  32. Fraguas, D. et al. Efficacy and safety of second-generation antipsychotics in children and adolescents with psychotic and bipolar spectrum disorders: Comprehensive review of prospective head-to-head and placebo-controlled comparisons. Eur. Neuropsychopharmacol. 21, 621–645 (2011).

    Article  CAS  PubMed  Google Scholar 

  33. McIntyre, R. S. & Jerrell, J. M. Metabolic and cardiovascular adverse events associated with antipsychotic treatment in children and adolescents. Arch. Pediatr. Adolesc. Med. 162, 929–935 (2008).

    Article  PubMed  Google Scholar 

  34. Jerrell, J. M. & McIntyre, R. S. Adverse events in children and adolescents treated with antipsychotic medications. Hum. Psychopharmacol. 23, 283–290 (2008).

    Article  PubMed  Google Scholar 

  35. Reynolds, G. P. & Kirk, S. L. Metabolic side effects of antipsychotic drug treatment—pharmacological mechanisms. Pharmacol. Ther. 125, 169–179 (2010).

    Article  CAS  PubMed  Google Scholar 

  36. Zyprexa® (olanzapine) prescribing information. Eli Lilly and Company [online], (2011).

  37. Bhargava, A. A longitudinal analysis of the risk factors for diabetes and coronary heart disease in the Framingham Offspring Study. Popul. Health. Metr. 1, 3 (2003).

    Article  PubMed  PubMed Central  Google Scholar 

  38. Grundy, S. M. Metabolic syndrome: connecting and reconciling cardiovascular and diabetes worlds. J. Am. Coll. Cardiol. 47, 1093–1100 (2006).

    Article  CAS  PubMed  Google Scholar 

  39. Arango, C. et al. A comparison of schizophrenia outpatients treated with antipsychotics with and without metabolic syndrome: Findings from the CLAMORS study. Schizophr. Res. 104, 1–12 (2008).

    Article  PubMed  Google Scholar 

  40. Foley, D. L. & Morley, K. I. Systematic review of early cardiometabolic outcomes of the first treated episode of psychosis. Arch. Gen. Psychiatry 68, 609–616 (2011).

    Article  PubMed  Google Scholar 

  41. De Hert, M. et al. Cardiovascular disease and diabetes in people with severe mental illness position statement from the European Psychiatric Association (EPA), supported by the European Association for the Study of Diabetes (EASD) and the European Society of Cardiology (ESC). Eur. Psychiatry 24, 412–424 (2009).

    Article  CAS  PubMed  Google Scholar 

  42. Nielsen, J., Skadhede, S. & Correll, C. U. Antipsychotics associated with the development of type 2 diabetes in antipsychotic-naive schizophrenia patients. Neuropsychopharmacology 35, 1997–2004 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, North American Association for the Study of Obesity. Consensus development conference on antipsychotic drugs and obesity and diabetes. J. Clin. Psychiatry 65, 267–272 (2004).

  44. Kessing, L. V., Thomsen, A. F., Mogensen, U. B. & Andersen, P. K. Treatment with antipsychotics and the risk of diabetes in clinical practice. Br. J. Psychiatry 197, 266–271 (2010).

    Article  PubMed  Google Scholar 

  45. Simon, V., van Winkel, R. & De Hert, M. Are weight gain and metabolic side effects of atypical antipsychotics dose dependent? A literature review. J. Clin. Psychiatry 70, 1041–1050 (2009).

    Article  CAS  PubMed  Google Scholar 

  46. Rummel-Kluge, C. et al. Head-to-head comparisons of metabolic side effects of second generation antipsychotics in the treatment of schizophrenia: a systematic review and meta-analysis. Schizophr. Res. 123, 225–233 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  47. De Hert, M., Schreurs, V., Vancampfort, D. & Van Winkel, R. Metabolic syndrome in people with schizophrenia: a review. World Psychiatry 8, 15–22 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  48. Vancampfort, D. et al. Relationships between obesity, functional exercise capacity, physical activity participation and physical self-perception in people with schizophrenia. Acta Psychiatr. Scand. 123, 423–430 (2011).

    Article  CAS  PubMed  Google Scholar 

  49. Vancampfort, D. et al. Considering a frame of reference for physical activity research related to the cardiometabolic risk profile in schizophrenia. Psychiatry Res. 177, 271–279 (2010).

    Article  PubMed  Google Scholar 

  50. Qin, L., Knol, M. J., Corpeleijn, E. & Stolk, R. P. Does physical activity modify the risk of obesity for type 2 diabetes: a review of epidemiological data. Eur. J. Epidemiol. 25, 5–12 (2010).

    Article  PubMed  Google Scholar 

  51. Hartemink, N., Boshuizen, H. C., Nagelkerke, N. J., Jacobs, M. A. & van Houwelingen, H. C. Combining risk estimates from observational studies with different exposure cutpoints: a meta-analysis on body mass index and diabetes type 2. Am. J. Epidemiol. 163, 1042–1052 (2006).

    Article  PubMed  Google Scholar 

  52. Alberti, K. G., Zimmet, P. & Shaw, J. International Diabetes Federation: a consensus on type 2 diabetes prevention. Diabet. Med. 24, 451–463 (2007).

    Article  CAS  PubMed  Google Scholar 

  53. Smith, M. et al. First- versus second-generation antipsychotics and risk for diabetes in schizophrenia: systematic review and meta-analysis. Br. J. Psychiatry 192, 406–411 (2008).

    Article  CAS  PubMed  Google Scholar 

  54. Liao, C. H. et al. Schizophrenia patients at higher risk of diabetes, hypertension and hyperlipidemia: a population-based study. Schizophr. Res. 126, 110–116 (2011).

    Article  PubMed  Google Scholar 

  55. Ramaswamy, K., Masand, P. S. & Nasrallah, H. A. Do certain atypical antipsychotics increase the risk of diabetes? A critical review of 17 pharmacoepidemiologic studies. Ann. Clin. Psychiatry 18, 183–194 (2006).

    Article  PubMed  Google Scholar 

  56. Yood, M. U. et al. The incidence of diabetes in atypical antipsychotic users differs according to agent—results from a multisite epidemiologic study. Pharmacoepidemiol. Drug Saf. 18, 791–799 (2009).

    Article  PubMed  Google Scholar 

  57. Starrenburg, F. C. & Bogers, J. P. How can antipsychotics cause diabetes mellitus? Insights based on receptor-binding profiles, humoral factors and transporter proteins. Eur. Psychiatry 24, 164–170 (2009).

    Article  CAS  PubMed  Google Scholar 

  58. Baker, R. A. et al. Atypical antipsychotic drugs and diabetes mellitus in the US Food and Drug Administration adverse event database: a systematic Bayesian signal detection analysis. Psychopharmacol. Bull. 42, 11–31 (2009).

    PubMed  Google Scholar 

  59. Bushe, C. J. & Leonard, B. E. Blood glucose and schizophrenia: a systematic review of prospective randomized clinical trials. J. Clin. Psychiatry 68, 1682–1690 (2007).

    Article  CAS  PubMed  Google Scholar 

  60. Hammerman, A. et al. Antipsychotics and diabetes: an age-related association. Ann. Pharmacother. 42, 1316–1322 (2008).

    Article  PubMed  Google Scholar 

  61. Panagiotopoulos, C., Ronsley, R. & Davidson, J. Increased prevalence of obesity and glucose intolerance in youth treated with second-generation antipsychotic medications. Can. J. Psychiatry 54, 743–749 (2009).

    Article  PubMed  Google Scholar 

  62. Kim, S. F., Huang, A. S., Snowman, A. M., Teuscher, C. & Snyder, S. H. From the cover: Antipsychotic drug-induced weight gain mediated by histamine H1 receptor-linked activation of hypothalamic AMP-kinase. Proc. Natl Acad. Sci. USA 104, 3456–3459 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Kroeze, W. K. et al. H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs. Neuropsychopharmacology 28, 519–526 (2003).

    Article  CAS  PubMed  Google Scholar 

  64. Correll, C. U. From receptor pharmacology to improved outcomes: individualizing the selection, dosing, and switching of antipsychotics. Eur. Psychiatry 25 (Suppl. 2), S12–S21 (2010).

    Article  PubMed  Google Scholar 

  65. Johnson, D. E. et al. The role of muscarinic receptor antagonism in antipsychotic-induced hippocampal acetylcholine release. Eur. J. Pharmacol. 506, 209–219 (2005).

    Article  CAS  PubMed  Google Scholar 

  66. Silvestre, J. S. & Prous, J. Research on adverse drug events. I. Muscarinic M3 receptor binding affinity could predict the risk of antipsychotics to induce type 2 diabetes. Methods Find. Exp. Clin. Pharmacol. 27, 289–304 (2005).

    Article  CAS  PubMed  Google Scholar 

  67. Bishara, D. & Taylor, D. Asenapine monotherapy in the acute treatment of both schizophrenia and bipolar I disorder. Neuropsychiatr. Dis. Treat. 5, 483–490 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Moons, T. et al. Clock genes and body composition in patients with schizophrenia under treatment with antipsychotic drugs. Schizophr. Res. 125, 187–193 (2011).

    Article  PubMed  Google Scholar 

  69. van Winkel, R. et al. MTHFR and risk of metabolic syndrome in patients with schizophrenia. Schizophr. Res. 121, 193–198 (2010).

    Article  PubMed  Google Scholar 

  70. van Winkel, R. et al. MTHFR genotype and differential evolution of metabolic parameters after initiation of a second generation antipsychotic: an observational study. Int. Clin. Psychopharmacol. 25, 270–276 (2010).

    Article  PubMed  Google Scholar 

  71. Balt, S. L., Galloway, G. P., Baggott, M. J., Schwartz, Z. & Mendelson, J. Mechanisms and genetics of antipsychotic-associated weight gain. Clin. Pharmacol. Ther. 90, 179–183 (2011).

    Article  CAS  PubMed  Google Scholar 

  72. Nasrallah, H. A. Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol. Psychiatry 13, 27–35 (2008).

    Article  CAS  PubMed  Google Scholar 

  73. Oh, K. J. et al. Atypical antipsychotic drugs perturb AMPK-dependent regulation of hepatic lipid metabolism. Am. J. Physiol. Endocrinol. Metab. 300, E624–E632 (2011).

    Article  CAS  PubMed  Google Scholar 

  74. Hennessy, S. et al. Cardiac arrest and ventricular arrhythmia in patients taking antipsychotic drugs: cohort study using administrative data. BMJ 325, 1070 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Straus, S. M. et al. Antipsychotics and the risk of sudden cardiac death. Arch. Intern. Med. 164, 1293–1297 (2004).

    Article  PubMed  Google Scholar 

  76. Ray, W. A., Chung, C. P., Murray, K. T., Hall, K. & Stein, C. M. Atypical antipsychotic drugs and the risk of sudden cardiac death. N. Engl. J. Med. 360, 225–235 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Manu, P., Kane, J. M. & Correll, C. U. Sudden deaths in psychiatric patients. J. Clin. Psychiatry 72, 936–941 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  78. Haddad, P. M. & Sharma, S. G. Adverse effects of atypical antipsychotics; differential risk and clinical implications. CNS Drugs 21, 911–936 (2007).

    Article  CAS  PubMed  Google Scholar 

  79. Elbe, D. & Savage, R. How does this happen? Part I: mechanisms of adverse drug reactions associated with psychotropic medications. J. Can. Acad. Child. Adolesc. Psychiatry 19, 40–45 (2010).

    PubMed  PubMed Central  Google Scholar 

  80. Reilly, J. G., Ayis, S. A., Ferrier, I. N., Jones, S. J. & Thomas, S. H. Thioridazine and sudden unexplained death in psychiatric in-patients. Br. J. Psychiatry 180, 515–522 (2002).

    Article  CAS  PubMed  Google Scholar 

  81. Thomas, S. H. et al. Safety of sertindole versus risperidone in schizophrenia: principal results of the sertindole cohort prospective study (SCoP). Acta Psychiatr. Scand. 122, 345–355 (2010).

    Article  CAS  PubMed  Google Scholar 

  82. Strom, B. L. et al. Comparative mortality associated with ziprasidone and olanzapine in real-world use among 18,154 patients with schizophrenia: The Ziprasidone Observational Study of Cardiac Outcomes (ZODIAC). Am. J. Psychiatry 168, 193–201 (2011).

    Article  PubMed  Google Scholar 

  83. Correll, C. U. & Nielsen, J. Antipsychotic-associated all-cause and cardiac mortality: what should we worry about and how should the risk be assessed? Acta Psychiatr. Scand. 122, 341–344 (2010).

    Article  PubMed  Google Scholar 

  84. Barnes, T. R. et al. A UK audit of screening for the metabolic side effects of antipsychotics in community patients. Schizophr. Bull. 33, 1397–1403 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  85. Lambert, T. J. & Newcomer, J. W. Are the cardiometabolic complications of schizophrenia still neglected? Barriers to care. Med. J. Aust. 190, S39–S42 (2009).

    Article  PubMed  Google Scholar 

  86. Hasnain, M., Fredrickson, S. K., Vieweg, W. V. & Pandurangi, A. K. Metabolic syndrome associated with schizophrenia and atypical antipsychotics. Curr. Diab. Rep. 10, 209–216 (2010).

    Article  PubMed  Google Scholar 

  87. Haupt, D. W. et al. Prevalence and predictors of lipid and glucose monitoring in commercially insured patients treated with second-generation antipsychotic agents. Am. J. Psychiatry 166, 345–353 (2009).

    Article  PubMed  Google Scholar 

  88. Kisely, S., Campbell, L. A. & Wang, Y. Treatment of ischaemic heart disease and stroke in individuals with psychosis under universal healthcare. Br. J. Psychiatry 195, 545–550 (2009).

    Article  PubMed  Google Scholar 

  89. Kisely, S. et al. Inequitable access for mentally ill patients to some medically necessary procedures. CMAJ 176, 779–784 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  90. Laursen, T. M., Munk-Olsen, T., Agerbo, E., Gasse, C. & Mortensen, P. B. Somatic hospital contacts, invasive cardiac procedures, and mortality from heart disease in patients with severe mental disorder. Arch. Gen. Psychiatry 66, 713–720 (2009).

    Article  PubMed  Google Scholar 

  91. Wheeler, A. J. et al. Cardiovascular risk assessment and management in mental health clients: whose role is it anyway? Community Ment. Health J. 46, 531–539 (2010).

    Article  PubMed  Google Scholar 

  92. Nasrallah, H. A. et al. Low rates of treatment for hypertension, dyslipidemia and diabetes in schizophrenia: data from the CATIE schizophrenia trial sample at baseline. Schizophr. Res. 86, 15–22 (2006).

    Article  PubMed  Google Scholar 

  93. De Hert, M. et al. The METEOR study of diabetes and other metabolic disorders in patients with schizophrenia treated with antipsychotic drugs. I. Methodology. Int. J. Methods Psychiatr. Res. 19, 195–210 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  94. Kilbourne, A. M., Welsh, D., McCarthy, J. F., Post, E. P. & Blow, F. C. Quality of care for cardiovascular disease-related conditions in patients with and without mental disorders. J. Gen. Intern. Med. 23, 1628–1633 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  95. Raedler, T. J. Cardiovascular aspects of antipsychotics. Curr. Opin. Psychiatry 23, 574–581 (2010).

    Article  PubMed  Google Scholar 

  96. Hippisley-Cox, J., Parker, C., Coupland, C. & Vinogradova, Y. Inequalities in the primary care of patients with coronary heart disease and serious mental health problems: a cross-sectional study. Heart 93, 1256–1262 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  97. Hennekens, C. H., Hennekens, A. R., Hollar, D. & Casey, D. E. Schizophrenia and increased risks of cardiovascular disease. Am. Heart J. 150, 1115–1121 (2005).

    Article  PubMed  Google Scholar 

  98. Fagiolini, A. & Goracci, A. The effects of undertreated chronic medical illnesses in patients with severe mental disorders. J. Clin. Psychiatry 70, 22–29 (2009).

    Article  PubMed  Google Scholar 

  99. Wahrenberg, H. et al. Use of waist circumference to predict insulin resistance: retrospective study. BMJ 330, 1363–1364 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  100. Straker, D. et al. Cost-effective screening for the metabolic syndrome in patients treated with second-generation antipsychotic medications. Am. J. Psychiatry 162, 1217–1221 (2005).

    Article  PubMed  Google Scholar 

  101. Ness-Abramof, R. & Apovian, C. M. Waist circumference measurement in clinical practice. Nutr. Clin. Pract. 23, 397–404 (2008).

    Article  PubMed  Google Scholar 

  102. Alberti, K. G. et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 120, 1640–1645 (2009).

    Article  CAS  PubMed  Google Scholar 

  103. Chobanian, A. V. et al. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 289, 2560–2572 (2003).

    Article  CAS  PubMed  Google Scholar 

  104. International Expert Committee. International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care 32, 1327–1334 (2009).

  105. Manu, P., Correll, C. U., van Winkel, R., Wampers, M. & De Hert, M. Prediabetes in patients treated with antipsychotic drugs. J. Clin. Psychiatry (in press).

  106. Fan, X. et al. Triglyceride/high-density lipoprotein cholesterol ratio: a surrogate to predict insulin resistance and low-density lipoprotein cholesterol particle size in nondiabetic patients with schizophrenia. J. Clin. Psychiatry 72, 806–812 (2011).

    Article  CAS  PubMed  Google Scholar 

  107. De Hert, M. et al. Treatment with rosuvastatin for severe dyslipidemia in patients with schizophrenia and schizoaffective disorder. J. Clin. Psychiatry 67, 1889–1896 (2006).

    Article  CAS  PubMed  Google Scholar 

  108. Hanssens, L. et al. Pharmacological treatment of severe dyslipidaemia in patients with schizophrenia. Int. Clin. Psychopharmacol. 22, 43–49 (2007).

    PubMed  Google Scholar 

  109. Perrin, J. M., Friedman, R. A., Knilans, T. K., Black Box Working Group & Section on Cardiology and Cardiac Surgery. Cardiovascular monitoring and stimulant drugs for attention-deficit/hyperactivity disorder. Pediatrics 22, 451–453 (2008).

    Article  Google Scholar 

  110. Vetter, V. L. et al. Cardiovascular monitoring of children and adolescents with heart disease receiving medications for attention deficit/hyperactivity disorder: a scientific statement form the American Heart Association Council on Cardiovascular Disease in the Young, Congenital Cardiac Defects Committee and the Council on Cardiovascular Nursing. Circulation 117, 2407–2423 (2008).

    Article  PubMed  Google Scholar 

  111. Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Education Program (NCEP) Expert Panel on Detection, Evaluation and treatment of High Blood Cholesterol (Adult Treatment Part III). JAMA 285, 2486–2497 (2001).

  112. De Hert, M. et al. Guidelines for screening and monitoring of cardiometabolic risk in schizophrenia: systematic evaluation. Brit. J. Psychiatry 199, 99–105 (2011).

    Article  CAS  Google Scholar 

  113. Correll, C. U. et al. QT interval duration and dispersion in children and adolescents treated with ziprasidone. J. Clin. Psychiatry 72, 854–860 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  114. Lehman, A. F. et al. Practice guideline for the treatment of patients with schizophrenia, second edition. Am. J. Psychiatry 161 (Suppl. 2), S1–S56 (2004).

    Google Scholar 

  115. Marder, S. R. et al. Physical health monitoring of patients with schizophrenia. Am. J. Psychiatry 161, 1334–1349 (2004).

    Article  PubMed  Google Scholar 

  116. European Heart Rhythm Association. et al. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing committee to develop guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death). J. Am. Coll. Cardiol. 48, e247–e346 (2006).

  117. Maayan, L. & Correll, C. U. Management of antipsychotic-related weight gain. Expert Rev. Neurother. 10, 1175–1200 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  118. Vreeland, B. Treatment decisions in major mental illness: weighing the outcomes. J. Clin. Psychiatry 68 (Suppl. 12), 5–11 (2007).

    PubMed  Google Scholar 

  119. Rossi, A. et al. Switching among antipsychotics in everyday clinical practice: focus on ziprasidone. Postgrad. Med. 123, 135–159 (2011).

    Article  PubMed  Google Scholar 

  120. Hermes, E. et al. The association between weight change and symptom reduction in the CATIE schizophrenia trial. Schizophr. Res. 128, 166–170 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. University Psychiatric Center, Catholic University Leuven, Leuvensesteenweg 517, Kortenberg, 3070, Belgium

    Marc De Hert, Johan Detraux & Weiping Yu

  2. Department of Psychiatry and Psychology, South Limburg Mental Health Research and Teaching Network, Maastricht University Medical Center, Vijverdalseweg 1, Maastricht, 6226, NB, The Netherlands

    Ruud van Winkel

  3.  The Zucker Hillside Hospital, Psychiatry Research, 75–59 263rd Street, Glen Oaks, 11004, NY, USA

    Christoph U. Correll

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  1. Marc De Hert
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  2. Johan Detraux
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  4. Weiping Yu
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  5. Christoph U. Correll
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Contributions

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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Correspondence to Marc De Hert.

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Competing interests

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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