, Volume 74, Issue 2, pp 183–194 | Cite as

Acute Hyperglycemia Associated with Short-Term Use of Atypical Antipsychotic Medications

  • T. Vivian LiaoEmail author
  • Stephanie V. Phan
Review Article


The prevalence of metabolic disturbances associated with long-term use of antipsychotic medications has been widely reported in the literature. The use of atypical antipsychotics for the treatment of delirium in the intensive care unit (ICU) has gained popularity due to a lower potential for adverse effects compared with conventional antipsychotics. However, current studies evaluating safety and efficacy of antipsychotics in the ICU setting do not include metabolic parameters as a potential adverse effect that requires monitoring. It is thought that long-term adverse effects of antipsychotics may be out of context for the intensive care setting. A literature review was conducted to investigate the prevalence of acute hyperglycemia associated with short-term use of antipsychotics, with the purpose of reviewing evidence that hyperglycemia may occur even with short-term use of atypical antipsychotics. A MEDLINE search for acute hyperglycemia from short-term use of antipsychotics resulted in studies involving animal models and healthy volunteers. These studies indicate that acute hyperglycemia may occur after short-term treatment. A review of the literature shows preliminary evidence to suggest that atypical antipsychotics impact glucose sensitivity and induce insulin resistance even after a single dose. Although no studies have been conducted evaluating the impact of hyperglycemia in critically ill patients from the short-term use of atypical antipsychotics for the treatment of delirium, the potential to affect clinical outcomes exist and warrants further research in this area.


Haloperidol Clozapine Risperidone Olanzapine Quetiapine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors would like to acknowledge John Papadopoulos, B.S., Pharm.D., FCCM, BCNSP for his assistance with reviewing and commenting on a draft of the manuscript.

Conflict of interest statement

T.V. Liao and S.V. Phan have no conflict of interest to report. No financial assistance was used to assist in the preparation of this manuscript. This work has not been presented previously.


  1. 1.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington: American Psychiatric Association; 2013.Google Scholar
  2. 2.
    Thomason JW, Shintani A, Peterson JF, et al. Intensive care unit delirium is an independent predictor of longer hospital stay: a prospective analysis of 261 non-ventilated patients. Crit Care Med. 2005;9(4):R375–81.CrossRefGoogle Scholar
  3. 3.
    Ely EW, Gautam S, Margolin R, et al. The impact of delirium in the intensive care unit on hospital length of stay. Intensive Care Med. 2001;27(12):1892–900 (Epub 2001 Nov 8).PubMedCrossRefGoogle Scholar
  4. 4.
    Lat I, McMillian W, Taylor S, et al. The impact of delirium on clinical outcomes in mechanically ventilated surgical and trauma patients. Crit Care Med. 2009;37(6):1898–905.PubMedCrossRefGoogle Scholar
  5. 5.
    Lin SM, Liu CY, Wang CH, et al. The impact of delirium on the survival of mechanically ventilated patients. Crit Care Med. 2004;32(11):2254–9.PubMedGoogle Scholar
  6. 6.
    Ely EW, Shintani A, Truman B, et al. Delirium as a predictor of mortality of in mechanically ventilated patients in the intensive care unit. JAMA. 2004;291(14):1753–62.PubMedCrossRefGoogle Scholar
  7. 7.
    Miller RR, Shintani A, Girard TD, et al. Delirium predicts extubation failure. Proc Am Thorac Soc. 2006;3:A42.Google Scholar
  8. 8.
    Jones SF, Pisani MA. ICU delirium: an update. Curr Opin Crit Care. 2012;18:146–51.PubMedCrossRefGoogle Scholar
  9. 9.
    Morandi A, Jackson JC, Ely EW. Delirium in the intensive care unit. Int Rev Psychiatry. 2009;21(1):43–58.PubMedCrossRefGoogle Scholar
  10. 10.
    Barr J, Fraser GL, Puntillo K, et al. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med. 2013;41:263–306.PubMedCrossRefGoogle Scholar
  11. 11.
    Rompaey BV, Schuurmans MJ, Shortridge-Baggett LM, et al. Risk factors for intensive care delirium: a systematic review. Intensive Crit Care Nurs. 2008;24:98–107.PubMedCrossRefGoogle Scholar
  12. 12.
    Rea RS, Battistone S, Fong JJ, et al. Atypical antipsychotics versus haloperidol for treatment of delirium in acutely ill patients. Pharmacotherapy. 2007;27(4):588–94.PubMedCrossRefGoogle Scholar
  13. 13.
    Page V, Gough K. Management of delirium in the intensive care unit. Brit J Hosp Med (Lond). 2010;71(7):372–6.Google Scholar
  14. 14.
    Jacobi J, Fraser GL, Coursin DB, et al. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Crit Care Med. 2002;30(1):119–41.PubMedCrossRefGoogle Scholar
  15. 15.
    Shapiro BA, Warren J, Egol AB, et al. Practice parameters for intravenous analgesia and sedation for adult patients in the intensive care unit: an executive summary. Society of Critical Care Medicine. Crit Care Med. 1995;23(9):1596–600.PubMedCrossRefGoogle Scholar
  16. 16.
    Haloperidol. DRUGDEX® System (version 5.1) [Intranet], 17 Dec 2013. Greenwood Village: Thomson Reuters (Healthcare) Inc.Google Scholar
  17. 17.
    Ely EW, Stephens RK, Jackson JC, et al. Current opinions regarding the importance, diagnosis, and management of delirium in the intensive care unit: a survey of 912 healthcare professionals. Crit Care Med. 2004;32:106–12.PubMedCrossRefGoogle Scholar
  18. 18.
    Patel RL, Gambrell MA, Speroff T, et al. Delirium and sedation in the intensive care unit (ICU): survey of behaviors and attitudes of 1,384 healthcare professionals. Crit Care Med. 2009;37:825–32.PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Devlin JW, Bhat S, Roberts RJ, et al. Current perceptions and practices surrounding the recognition and treatment of delirium in the intensive care unit: a survey of 250 critical care pharmacists from eight states. Ann Pharmacother. 2011;45(10):1217–29.PubMedCrossRefGoogle Scholar
  20. 20.
    Girard TD, Pandharipande PP, Carson SS, et al. Feasibility, efficacy, and safety of antipsychotics for intensive care unit delirium: the MIND randomized, placebo-controlled trial. Crit Care Med. 2010;38(2):428–37.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Devlin JW, Roberts RJ, Fong JJ, et al. Efficacy and safety of quetiapine in critically ill patients with delirium: a prospective, multicenter, randomized, double-blind, placebo-controlled pilot study. Crit Care Med. 2010;38(2):1–9.CrossRefGoogle Scholar
  22. 22.
    Skrobik YK, Bergeron N, Dumont M, Gottfried SB. Olanzapine vs haloperidol: treating delirium in a critical care setting. Intensive Care Med. 2004;30:444–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Gilchrist NA, Asoh I, Greenberg B. Atypical antipsychotics for the treatment of ICU delirium. J Intensive Care Med. 2012;27(6):354–61.PubMedCrossRefGoogle Scholar
  24. 24.
    Doucette DE, Grenier JP, Robertson PS. Olanzapine-induced pancreatitis. Ann Pharmacother. 2000;34(10):1128–31.PubMedCrossRefGoogle Scholar
  25. 25.
    Williams SG, Alinejad MA, Williams JA, et al. Statistically significant increase in weight caused by low-dose quetiapine. Pharmacotherapy. 2010;30(10):1011–5.PubMedCrossRefGoogle Scholar
  26. 26.
    Makhzoumi ZH, McLean LP, Lee JH, et al. Diabetic ketoacidosis associated with aripiprazole. Pharmacotherapy. 2008;28(9):1198–202.PubMedCrossRefGoogle Scholar
  27. 27.
    Seaburg HL, McLendon BM, Doraiswamy PM. Olanzapine-associated severe hyperglycemia, ketonuria, and acidosis: case report and review of literature. Pharmacotherapy. 2001;21(11):1448–54.PubMedCrossRefGoogle Scholar
  28. 28.
    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. Diabetes Care. 2004;27:596–601.Google Scholar
  29. 29.
    Savoy YE, Ashton MA, Miller MW, et al. Differential effects of various typical and atypical antipsychotics on plasma glucose and insulin levels in the mouse: evidence for the involvement of sympathetic regulation. Schizophr Bull. 2010;36(2):410–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Tschoner A, Engl J, Laimer M, Kaser S, Rettenbacher M, Fleischhacker WW, et al. Metabolic side effects of antipsychotic medication. Int J Clin Prac. 2007;61(8):1356–70.CrossRefGoogle Scholar
  31. 31.
    Haupt DW, Newcomer JW. Hyperglycemia and antipsychotic medications. J Clin Psychiatry. 2001;62(suppl 27):15–26.PubMedGoogle Scholar
  32. 32.
    Houseknecht KL, Robertson AS, Zavadoski W, et al. Acute effects of atypical antipsychotics on whole-body insulin resistance in rats: implications for adverse metabolic effects. Neuropsychopharmacology. 2007;32:289–97.PubMedCrossRefGoogle Scholar
  33. 33.
    Newcomer JW. Metabolic considerations in the use of antipsychotic medications: a review of recent evidence. J Clin Psychiatry. 2007;68(suppl 1):20–7.PubMedGoogle Scholar
  34. 34.
    Boyda HN, Tse L, Procyshyn RM, et al. A parametric study of the acute effects of antipsychotic drugs on glucose sensitivity in an animal model. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34(6):945–54.PubMedCrossRefGoogle Scholar
  35. 35.
    Koller EA, Weber J, Doraiswamy PM, et al. A survey of reports of quetiapine-associated hyperglycemia and diabetes mellitus. J Clin Psychiatry. 2004;65:857–63.PubMedCrossRefGoogle Scholar
  36. 36.
    Dwyer DS, Donohoe D. Induction of hyperglycemia in mice with atypical antipsychotic drugs that inhibit glucose uptake. Pharmacol Biochem Behav. 2003;75(2):255–60.PubMedGoogle Scholar
  37. 37.
    Chintoh AF, Mann SW, Lam L, et al. Insulin resistance and decreased glucose-stimulated insulin secretion after acute olanzapine administration. J Clin Psychopharmacol. 2008;28(5):494–9.PubMedCrossRefGoogle Scholar
  38. 38.
    Smith GC, Chaussade C, Vickers M, et al. Atypical antipsychotic drugs induce derangements in glucose homeostasis by acutely increasing glucagon secretion and hepatic glucose output in the rat. Diabetologia. 2008;51(12):2309–17.PubMedCrossRefGoogle Scholar
  39. 39.
    Jassim G, Skrede S, Vázquez MJ, et al. Acute effects of orexigenic antipsychotic drugs on lipid and carbohydrate metabolism in rat. Psychopharmacology (Berl). 2012;219(3):783–94 (Epub 2011 Jul 12).PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Chintoh AF, Mann SW, Lam L, et al. Insulin resistance and secretion in vivo: effects of different antipsychotics in an animal model. Schizophr Res. 2009;108:127–33.PubMedCrossRefGoogle Scholar
  41. 41.
    Girault EM, Alkemade A, Foppen E, et al. Acute peripheral but not central administration of olanzapine induces hyperglycemia associated with hepatic and extra-hepatic insulin resistance. PLoS One. 2012;7(8):e43244.PubMedCentralPubMedCrossRefGoogle Scholar
  42. 42.
    Martins PJ, Haas M, Obici S. Central nervous system delivery of the antipsychotic olanzapine induces hepatic insulin resistance. Diabetes. 2010;59(10):2418–25.PubMedCrossRefGoogle Scholar
  43. 43.
    Bergman RN, Hope ID, Yang YJ, et al. Assessment of insulin sensitivity in vivo: a critical review. Diabetes Metab Rev. 1989;5:411–29.PubMedCrossRefGoogle Scholar
  44. 44.
    Muniyappa R, Lee S, Chen H, et al. Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage. Am J Physiol Endocrinol Metab. 2008;294(1):E15–26.PubMedGoogle Scholar
  45. 45.
    Roefaro J, Mukherjee SM. Olanzapine-induced hyperglycemic nonketonic coma. Ann Pharmacother. 2001;35:300–2.PubMedCrossRefGoogle Scholar
  46. 46.
    Ramankutty G. Olanzapine-induced destabilization of diabetes in the absence of weight gain. Acta Psychiatr Scand. 2002;105(3):235–6 (discussion 236–7).Google Scholar
  47. 47.
    Bettinger TL, Mendelson SC, Dorson PG, et al. Olanzapine-induced glucose dysregulation. Ann Pharmacother. 2000;34(7–8):865–7.PubMedCrossRefGoogle Scholar
  48. 48.
    Ober SK, Hudak R, Rusterholtz A. Hyperglycemia and olanzapine. Am J Psychiatry. 1999;156(6):970.PubMedGoogle Scholar
  49. 49.
    Kohen I, Gampel M, Reddy L, et al. Rapidly developing hyperglycemia during treatment with olanzapine. Ann Pharamcother. 2008;42:588–91.CrossRefGoogle Scholar
  50. 50.
    Goldstein LE, Sporn J, Brown S, et al. New-onset diabetes mellitus and diabetic ketoacidosis associated with olanzapine treatment. Psychomatics. 1999;40(5):438–43.CrossRefGoogle Scholar
  51. 51.
    Chiu C, Chen K, Liu H, et al. The early effect of olanzapine and risperidone on insulin secretion in atypical-naïve schizophrenic patients. J Clin Psychopharmacol. 2006;26:504–7.PubMedCrossRefGoogle Scholar
  52. 52.
    Sacher J, Mossaheb N, Spindelegger C, et al. Effects of olanzapine and ziprasidone on glucose tolerance in healthy volunteers. Neuropsychopharmacology. 2008;33(7):1633–41.PubMedCrossRefGoogle Scholar
  53. 53.
    Vidarsdottir S, de Leeuw van Weenen JE, Frölich M, et al. Effects of olanzapine and haloperidol on the metabolic status of healthy men. J Clin Endocrinol Metab. 2010;95:118–25.Google Scholar
  54. 54.
    Albaugh VL, Singareddy R, Mauger D, et al. A double blind, placebo-controlled, randomized crossover study of the acute metabolic effects of olanzapine in healthy volunteers. PLoS One. 2011;6(8):e22662.PubMedCentralPubMedCrossRefGoogle Scholar
  55. 55.
    Kopf D, Gilles M, Paslakis G, et al. Insulin secretion and sensitivity after single-dose amisulpride, olanzapine or placebo in young male subjects: double blind, cross-over glucose clamp study. Pharmacopsychiatry. 2012;45(6):223–8.PubMedCrossRefGoogle Scholar
  56. 56.
    Mac Sweeney R, Barber V, Page V, et al. A national survey of the management of delirium in UK intensive care units. QJM. 2010;103:243–51.Google Scholar
  57. 57.
    NICE-SUGAR Study Investigators, Finfer S, Chittock DR, et al. Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 2009;360:1283–97.Google Scholar
  58. 58.
    American Diabetes Association. Standards of medical care in diabetes—2012. Diabetes Care. 2012;35(Suppl 1):S11–63.Google Scholar
  59. 59.
    Moghissi ES, Korytkowski MT, DiNardo M, American Association of Clinical Endocrinologists, American Diabetes Association, et al. American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control. Diabetes Care. 2009;32:1119–31.Google Scholar
  60. 60.
    Capes SE, Hunt D, Malmberg K, et al. Stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview. Lancet. 2000;355:773–8.PubMedCrossRefGoogle Scholar
  61. 61.
    Gale SC, Sicoutris C, Reilly PM, et al. Poor glycemic control is associated with increased mortality in critically ill trauma patients. Am Surg. 2007;73(5):454–60.PubMedGoogle Scholar
  62. 62.
    Malone JI, Hanna S, Saporta S, et al. Hyperglycemia not hypoglycemia alters neuronal dendrites and impairs spatial memory. Pediatr Diabetes. 2008;9:531–9.PubMedCrossRefGoogle Scholar
  63. 63.
    Broderick JP, Diringer MN, Hill MD, et al.; Recombinant Activated Factor VII Intracerebral Hemorrhage Trial Investigators. Determinants of intracerebral hemorrhage growth: an exploratory analysis. Stroke. 2007;38:1072–5.Google Scholar
  64. 64.
    Tetri S, Juvela S, Saloheimo P, et al. Hypertension and diabetes as predictors of early death after spontaneous intracerebral hemorrhage. J Neurosurg. 2009;110:411–7.PubMedCrossRefGoogle Scholar
  65. 65.
    Egi M, Bellomo R, Stachowski E, et al. Variability of blood glucose concentration and short-term mortality in critically ill patients. Anesthesiology. 2006;105:244–52.PubMedCrossRefGoogle Scholar
  66. 66.
    Al-Dorzi HM, Tamim HM, Arabi YM. Glycaemic fluctuation predicts mortality in critically ill patients. Anaesth Intensive Care. 2010;38(4):695–702.PubMedGoogle Scholar
  67. 67.
    Gornik I, Vujaklija-Brajkovic A, Renar IP, et al. A prospective observational study of the relationship of critical illness associated hyperglycaemia in medical ICU patients and subsequent development of type 2 diabetes. Crit Care. 2010;14(4):R130.PubMedCrossRefGoogle Scholar
  68. 68.
    Duning T, van den Heuvel I, Dickmann A, et al. Hypoglycemia aggravates critical illness-induced neurocognitive dysfunction. Diabetes Care. 2010;33(3):639–44.PubMedCrossRefGoogle Scholar
  69. 69.
    Hopkins RO, Suchyta MR, Snow GL, et al. Blood glucose dysregulation and cognitive outcome in ARDS survivors. Brain Inj. 2010;24(12):1478–84.PubMedCrossRefGoogle Scholar
  70. 70.
    Pandharipande PP, Girard TD, Jackson JC, et al. Long-term cognitive impairment after critical illness. N Engl J Med. 2013;369(14):1306–16.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  1. 1.Mercer University College of PharmacyAtlantaUSA
  2. 2.University of Georgia College of Pharmacy, Southwest Georgia Clinical CampusAlbanyUSA

Personalised recommendations