Skip to main content
SpringerLink
Log in

Weight Gain and Changes in Metabolic Variables following Olanzapine Treatment in Schizophrenia and Bipolar Disorder

  • Review Article
  • Published:
Clinical Drug Investigation Aims and scope Submit manuscript

Abstract

Antipsychotic therapy forms the cornerstone of treatment for people with severe mental illness. Second-generation (atypical) antipsychotics are associated with a significantly lower incidence of extrapyramidal symptoms than the typical, first-generation agents; however, changes in metabolic variables — including impaired glucose metabolism, diabetes mellitus, weight gain and dyslipidaemia — have been reported during treatment with second-generation antipsychotics. Understanding any potential link between antipsychotic treatment and the incidence of these events is complicated by the increasing prevalence of obesity and diabetes occurring in the general population and the increased risk of diabetes and changes in metabolic variables in people with schizophrenia. While relative risk estimates are inconsistent, the association between atypical antipsychotics and increases in glucose level appears to fall on a continuum, with olanzapine appearing to have a greater association than some other atypical antipsychotics. The PubMed database was used to search for publications that included any information on measures of changes in weight, body mass index (BMI) and/or metabolic variables in randomized studies of olanzapine published between 1992 and 2010. In longterm (≥48 weeks) studies of olanzapine, the mean weight gain was 5.6 kg (last observation carried forward; median exposure 573 days). The proportions of patients who gained at least 7%, 15% or 25% of their baseline weight with long-term exposure were 64%, 32% and 12%, respectively. Some studies have suggested that weight gain early during the course of olanzapine treatment may predict clinically significant weight gain following long-term exposure to the drug. Changes in metabolic variables, such as elevated indices of glucose metabolism and triglyceride level, have also been observed during treatment with olanzapine. Consensus guidelines emphasize the importance of appropriate baseline screening and ongoing monitoring of weight gain and metabolic variables for people receiving all antipsychotic treatments. Long-term weight management programmes have been shown to reduce weight gain in some patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Table II
Fig. 1
Fig. 2
Table III

Similar content being viewed by others

References

  1. National Institute for Clinical Excellence (NICE). Schizophrenia: core interventions in the treatment and management of schizophrenia in primary and secondary care. Clinical guidelines CG82, March 2009 [online]. Available from URL: http://www.nice.org.uk/nicemedia/live/11786/43608/43608.pdf [Accessed 2009 Dec 29]

  2. National Institute for Clinical Excellence (NICE). Bipolar disorder: the management of bipolar disorder in adults, children and adolescents, in primary and secondary care. Clinical guidelines CG38, October 2006 [online]. Available from URL: http://www.nice.org.uk/nicemedia/pdf/CG38niceguideline.pdf [Accessed 2009 Dec 29]

  3. Gentile S. Long-term treatment with atypical antipsychotics and the risk of weight gain: a literature analysis. Drug Saf 2006; 29(4): 303–19

    Article  PubMed  CAS  Google Scholar 

  4. Newcomer JW. Second-generation (atypical) antipsychotics and metabolic effects: a comprehensive literature review. CNS Drugs 2005; 19Suppl. 1: 1–93

    PubMed  CAS  Google Scholar 

  5. Weiden PJ, Mackell JA, McDonnell DD. Obesity as a risk factor for antipsychotic noncompliance. Schizophr Res 2004 Jan 1; 66(1): 51–7

    Article  PubMed  Google Scholar 

  6. Thakore JH. Metabolic disturbance in first-episode schizophrenia. Br J Psychiatry Suppl 2004 Apr; 47: S76–9

    Article  PubMed  Google Scholar 

  7. Ogden CL, Carroll MD, McDowell MA, et al. Obesity among adults in the United States: no statistically significant change since 2003–2004. NCHS data brief no 1. Hyattsville (MD): National Center for Health Statistics, 2007 [online]. Available from URL: http://www.cdc.gov/nchs/data/databriefs/db01.pdf [Accessed 2009 Dec 29]

    Google Scholar 

  8. Centers for Disease Control and Prevention. Early release of selected estimates based on data from the 2002 National Health Interview Survey [online]. Available from URL: http://www.cdc.gov/nchs/nhis/released200306.htm [Accessed 2009 Dec 29]

  9. Cowie CC, Rust KF, Ford ES, et al. Full accounting of diabetes and pre-diabetes in the U.S. population in 1988–1994 and 2005–2006. Diabetes Care 2009 Feb; 32(2): 287–94

    Article  PubMed  Google Scholar 

  10. Albaugh VL, Henry CR, Bello NT, et al. Hormonal and metabolic effects of olanzapine and clozapine related to body weight in rodents. Obesity (Silver Spring) 2006 Jan; 14(1): 36–51

    Article  CAS  Google Scholar 

  11. Amamoto T, Kumai T, Nakaya S, et al. The elucidation of the mechanism of weight gain and glucose tolerance abnormalities induced by chlorpromazine. J Pharmacol Sci 2006 Oct; 102(2): 213–9

    Article  PubMed  CAS  Google Scholar 

  12. Kroeze WK, Hufeisen SJ, Popadak BA, et al. H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs. Neuropsychopharmacology 2003 Mar; 28(3): 519–26

    Article  PubMed  CAS  Google Scholar 

  13. Reynolds GP, Templeman LA, Zhang ZJ. The role of 5-HT2C receptor polymorphisms in the pharmacogenetics of antipsychotic drug treatment. Prog Neuropsychopharmacol Biol Psychiatry 2005 Jul; 29(6): 1021–8

    Article  PubMed  CAS  Google Scholar 

  14. Nilsson BM, Forslund AH, Olsson RM, et al. Differences in resting energy expenditure and body composition between patients with schizophrenia and healthy controls. Acta Psychiatr Scand 2006 Jul; 114(1): 27–35

    Article  PubMed  CAS  Google Scholar 

  15. Strassnig M, Brar JS, Ganguli R. Nutritional assessment of patients with schizophrenia: a preliminary study. Schizophr Bull 2003; 29(2): 393–7

    Article  PubMed  Google Scholar 

  16. Citrome L. Quantifying risk: the role of absolute and relative measures in interpreting risk of adverse reactions from product labels of antipsychotic medications. Curr Drug Saf 2009 Sep; 4(3): 229–37

    Article  PubMed  Google Scholar 

  17. Citrome L. Asenapine for schizophrenia and bipolar disorder: a review of the efficacy and safety profile for this newly approved sublingually absorbed second-generation antipsychotic. Int J Clin Pract 2009 Dec; 63(12): 1762–84

    Article  PubMed  CAS  Google Scholar 

  18. Citrome L. Paliperidone palmitate: review of the efficacy, safety and cost of a new second-generation depot antipsychotic medication. Int J Clin Pract 2010 Jan; 64(2): 216–39

    Article  PubMed  CAS  Google Scholar 

  19. Citrome L. Iloperidone redux: a dissection of the Drug Approval Package for this newly commercialised secondgeneration antipsychotic. Int J Clin Pract 2010 May; 64(6): 707–18

    Article  PubMed  CAS  Google Scholar 

  20. Beasley Jr CM, Tollefson G, Tran P, et al. Olanzapine versus placebo and haloperidol: acute phase results of the North American double-blind olanzapine trial. Neuropsychopharmacology 1996 Feb; 14(2): 111–23

    Article  PubMed  CAS  Google Scholar 

  21. Tollefson GD, Beasley Jr CM, Tran PV, et al. Olanzapine versus haloperidol in the treatment of schizophrenia and schizoaffective and schizophreniform disorders: results of an international collaborative trial. Am J Psychiatry 1997 Apr; 154(4): 457–65

    PubMed  CAS  Google Scholar 

  22. Tohen M, Sanger TM, McElroy SL, et al. Olanzapine versus placebo in the treatment of acute mania. Olanzapine HGEH Study Group. Am J Psychiatry 1999 May; 156(5): 702–9

    PubMed  CAS  Google Scholar 

  23. Tohen M, Jacobs TG, Grundy SL, et al. Efficacy of olanzapine in acute bipolar mania: a double-blind, placebocontrolled study. The Olanzapine HGGW Study Group. Arch Gen Psychiatry 2000 Sep; 57(9): 841–9

    Article  PubMed  CAS  Google Scholar 

  24. Tohen M, Baker RW, Altshuler LL, et al. Olanzapine versus divalproex in the treatment of acute mania. Am J Psychiatry 2002 Jun; 159(6): 1011–7

    Article  PubMed  Google Scholar 

  25. Tohen M, Vieta E, Goodwin GM, et al. Olanzapine versus divalproex versus placebo in the treatment of mild to moderate mania: a randomized, 12-week, double-blind study. J Clin Psychiatry 2008; 69(11): 1776–89

    Article  PubMed  CAS  Google Scholar 

  26. Zajecka JM, Weisler R, Sachs G, et al. A comparison of the efficacy, safety, and tolerability of divalproex sodium and olanzapine in the treatment of bipolar disorder. J Clin Psychiatry 2002 Dec; 63(12): 1148–55

    Article  PubMed  CAS  Google Scholar 

  27. Krakowski M, Czobor P, Citrome L. Weight gain, metabolic parameters, and the impact of race in aggressive inpatients randomized to double-blind clozapine, olanzapine, or haloperidol. Schizophr Res 2009 May; 110(1–3): 95–102

    Article  PubMed  Google Scholar 

  28. Tohen M, Goldberg JF, Gonzalez-Pinto Arrillaga AM, et al. A 12-week, double-blind comparison of olanzapine vs haloperidol in the treatment of acute mania. Arch Gen Psychiatry 2003 Dec; 60(12): 1218–26

    Article  PubMed  CAS  Google Scholar 

  29. Kelly DL, Conley RR, Love RC, et al. Metabolic risk with second-generation antipsychotic treatment: a doubleblind randomized 8-week trial of risperidone and olanzapine. Ann Clin Psychiatry 2008 Apr–Jun; 20(2): 71–8

    Article  PubMed  Google Scholar 

  30. Perlis RH, Baker RW, Zarate Jr CA, et al. Olanzapine versus risperidone in the treatment of manic or mixed states in bipolar I disorder: a randomized, double-blind trial. J Clin Psychiatry 2006 Nov; 67(11): 1747–53

    Article  PubMed  CAS  Google Scholar 

  31. Kinon BJ, Volavka J, Bergstom RF, et al. Steady state concentrations after standard and higher doses of oral olanzapine in acutely ill patients with schizophrenia or schizoaffective disorder with suboptimal prior response [abstract]. Neuropsychopharmacology 2006; 31Suppl. 1s: S115–6

    Google Scholar 

  32. Allison DB, Mentore JL, Heo M, et al. Antipsychoticinduced weight gain: a comprehensive research synthesis. Am J Psychiatry 1999 Nov; 156(11): 1686–96

    PubMed  CAS  Google Scholar 

  33. Bushe CJ, Leonard BE. Blood glucose and schizophrenia: a systematic review of prospective randomized clinical trials. J Clin Psychiatry 2007 Nov; 68(11): 1682–90

    Article  PubMed  CAS  Google Scholar 

  34. Ader M, Garvey WT, Phillips LS, et al. Ethnic heterogeneity in glucoregulatory function during treatment with atypical antipsychotics in patients with schizophrenia. J Psychiatr Res 2008 Oct; 42(13): 1076–85

    Article  PubMed  Google Scholar 

  35. Beasley Jr CM, Sutton VK, Hamilton SH, et al. A doubleblind, randomized, placebo-controlled trial of olanzapine in the prevention of psychotic relapse. J Clin Psychopharmacol 2003 Dec; 23(6): 582–94

    Article  PubMed  CAS  Google Scholar 

  36. Breier A, Berg PH, Thakore JH, et al. Olanzapine versus ziprasidone: results of a 28-week double-blind study in patients with schizophrenia. Am J Psychiatry 2005 Oct; 162(10): 1879–87

    Article  PubMed  Google Scholar 

  37. Argo TR, Carnahan RM, Perry PJ. Aripiprazole, a novel atypical antipsychotic drug. Pharmacotherapy 2004 Feb; 24(2): 212–28

    Article  PubMed  CAS  Google Scholar 

  38. Bushe C, Leonard B. Association between atypical antipsychotic agents and type 2 diabetes: review of prospective clinical data. Br J Psychiatry 2004 Apr; 184Suppl. 47: S87–93

    Article  Google Scholar 

  39. Chrzanowski WK, Marcus RN, Torbeyns A, et al. Effectiveness of long-term aripiprazole therapy in patients with acutely relapsing or chronic, stable schizophrenia: a 52-week, open-label comparison with olanzapine. Psychopharmacology (Berl) 2006 Dec; 189(2): 259–66

    Article  CAS  Google Scholar 

  40. Green AI, Lieberman JA, Hamer RM, et al. Olanzapine and haloperidol in first episode psychosis: two-year data. Schizophr Res 2006 Sep; 86(1–3): 234–43

    Article  PubMed  CAS  Google Scholar 

  41. Zipursky RB, Gu H, Green AI, et al. Course and predictors of weight gain in people with first-episode psychosis treated with olanzapine or haloperidol. Br J Psychiatry 2005 Dec; 187: 537–43

    Article  PubMed  Google Scholar 

  42. Kahn RS, Fleischhacker WW, Boter H, et al. Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial. Lancet 2008 Mar; 371(9618): 1085–97

    Article  PubMed  CAS  Google Scholar 

  43. Kinon BJ, Lipkovich I, Edwards SB, et al. A 24-week randomized study of olanzapine versus ziprasidone in the treatment of schizophrenia or schizoaffective disorder in patients with prominent depressive symptoms. J Clin Psychopharmacol 2006 Apr; 26(2): 157–62

    Article  PubMed  CAS  Google Scholar 

  44. Kinon BJ, Noordsy DL, Liu-Seifert H, et al. Randomized, double-blind 6-month comparison of olanzapine and quetiapine in patients with schizophrenia or schizoaffective disorder with prominent negative symptoms and poor functioning. J Clin Psychopharmacol 2006 Oct; 26(5): 453–61

    Article  PubMed  CAS  Google Scholar 

  45. Bushe C, Poole-Hoffman V, Lipkovich I. Metabolic comparisons from a 6-month randomized trial of olanzapine and quetiapine in schizophrenia [abstract no. 255]. Biol Psychiatry 2007; 61Suppl. 1: 80S

    Google Scholar 

  46. Bushe C, Sniadecki J, Bradley A, et al. Comparison of metabolic and prolactin variables from a six-month randomised trial of olanzapine and quetiapine in schizophrenia. J Psychopharmacol 2010 Jul; 24(7): 1001–9

    Article  PubMed  CAS  Google Scholar 

  47. Lieberman JA, Tollefson G, Tohen M, et al. Comparative efficacy and safety of atypical and conventional antipsychotic drugs in first-episode psychosis: a randomized, double-blind trial of olanzapine versus haloperidol. Am J Psychiatry 2003 Aug; 160(8): 1396–404

    Article  PubMed  Google Scholar 

  48. Lieberman JA, Stroup TS, McEvoy JP, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005 Sep; 353(12): 1209–23

    Article  PubMed  CAS  Google Scholar 

  49. Lindenmayer JP, Czobor P, Volavka J, et al. Changes in glucose and cholesterol levels in patients with schizophrenia treated with typical or atypical antipsychotics. Am J Psychiatry 2003 Feb; 160(2): 290–6

    Article  PubMed  Google Scholar 

  50. McEvoy JP, Lieberman JA, Perkins DO, et al. Efficacy and tolerability of olanzapine, quetiapine, and risperidone in the treatment of early psychosis: a randomized, doubleblind 52-week comparison. Am J Psychiatry 2007 Jul; 164(7): 1050–60

    Article  PubMed  Google Scholar 

  51. McQuade RD, Stock E, Marcus R, et al. A comparison of weight change during treatment with olanzapine or aripiprazole: results from a randomized, double-blind study. J Clin Psychiatry 2004; 65Suppl. 18: 47–56

    PubMed  CAS  Google Scholar 

  52. Meltzer HY, Alphs L, Green AI, et al. Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention Trial (InterSePT). Arch Gen Psychiatry 2003 Jan; 60(1): 82–91

    Article  PubMed  CAS  Google Scholar 

  53. Newcomer JW, Ratner RE, Eriksson JW, et al. A 24-week, multicenter, open-label, randomized study to compare changes in glucose metabolism in patients with schizophrenia receiving treatment with olanzapine, quetiapine, or risperidone. J Clin Psychiatry 2009 Apr; 70(4): 487–99

    Article  PubMed  CAS  Google Scholar 

  54. Perez-Iglesias R, Crespo-Facorro B, Amado JA, et al. A 12-week randomized clinical trial to evaluate metabolic changes in drug-naive, first-episode psychosis patients treated with haloperidol, olanzapine, or risperidone. J Clin Psychiatry 2007 Nov; 68(11): 1733–40

    Article  PubMed  Google Scholar 

  55. Perez-Iglesias R, Mata I, Pelayo-Teran JM, et al. Glucose and lipid disturbances after 1 year of antipsychotic treatment in a drug-naïve population. Schizophr Res 2009 Feb; 107(2–3): 115–21

    Article  PubMed  Google Scholar 

  56. Peuskens J, De Hert M, Mortimer A. Metabolic control in patients with schizophrenia treated with amisulpride or olanzapine. Int Clin Psychopharmacol 2007 May; 22(3): 145–52

    Article  PubMed  Google Scholar 

  57. Rosenheck R, Perlick D, Bingham S, et al. Effectiveness and cost of olanzapine and haloperidol in the treatment of schizophrenia: a randomized controlled trial. JAMA 2003 Nov; 290(20): 2693–702

    Article  PubMed  CAS  Google Scholar 

  58. Simpson GM, Glick ID, Weiden PJ, et al. Randomized, controlled, double-blind multicenter comparison of the efficacy and tolerability of ziprasidone and olanzapine in acutely ill inpatients with schizophrenia or schizoaffective disorder. Am J Psychiatry 2004 Oct; 161(10): 1837–47

    Article  PubMed  Google Scholar 

  59. Simpson GM, Weiden P, Pigott T, et al. Six-month, blinded, multicenter continuation study of ziprasidone versus olanzapine in schizophrenia. Am J Psychiatry 2005 Aug; 162(8): 1535–8

    Article  PubMed  Google Scholar 

  60. Smith RC, Lindenmayer JP, Davis JM, et al. Effects of olanzapine and risperidone on glucose metabolism and insulin sensitivity in chronic schizophrenic patients with long-term antipsychotic treatment: a randomized 5-month study. J Clin Psychiatry 2009 Nov; 70(11): 1501–13

    Article  PubMed  CAS  Google Scholar 

  61. Clinicalstudyresults.org. CN138003: a multicenter, doubleblind, randomized comparative study of aripiprazole and olanzapine in the treatment of patients with acute schizophrenia [online]. Available from URL: www.clinicalstudyresults.org/documents/company-study_1909_3.pdf. [Accessed 2007 Aug 20]

  62. Fleischhacker WW, McQuade RD, Marcus RN, et al. A double-blind, randomized comparative study of aripiprazole and olanzapine in patients with schizophrenia. Biol Psychiatry 2009 Mar; 65(6): 510–7

    Article  PubMed  CAS  Google Scholar 

  63. Tran PV, Hamilton SH, Kuntz AJ, et al. Double-blind comparison of olanzapine versus risperidone in the treatment of schizophrenia and other psychotic disorders. J Clin Psychopharmacol 1997 Oct; 17(5): 407–18

    Article  PubMed  CAS  Google Scholar 

  64. Vanelle JM, Douki S. A double-blind randomised comparative trial of amisulpride versus olanzapine for 2 months in the treatment of subjects with schizophrenia and comorbid depression. Eur Psychiatry 2006 Dec; 21(8): 523–30

    Article  PubMed  Google Scholar 

  65. Tohen M, Ketter TA, Zarate CA, et al. Olanzapine versus divalproex sodium for the treatment of acute mania and maintenance of remission: a 47-week study. Am J Psychiatry 2003 Jul; 160(7): 1263–71

    Article  PubMed  Google Scholar 

  66. Tohen M, Chengappa KN, Suppes T, et al. Relapse prevention in bipolar I disorder: 18-month comparison of olanzapine plus mood stabiliser v. mood stabiliser alone. Br J Psychiatry 2004 Apr; 184: 337–45

    Article  PubMed  Google Scholar 

  67. Tohen M, Greil W, Calabrese JR, et al. Olanzapine versus lithium in the maintenance treatment of bipolar disorder: a 12-month, randomized, double-blind, controlled clinical trial. Am J Psychiatry 2005 Jul; 162(7): 1281–90

    Article  PubMed  Google Scholar 

  68. Dossenbach M, Pachecho Z, Toledo D, et al. Patterns of antipsychotic-induced weight change: 3-year results from the intercontinental schizophrenia outpatient-health outcomes (IC-SOHO) study [abstract no. P.3.c.021]. Eur Neuropsychopharmacol 2006 Sep 16–20; 16Suppl. 4: S407–8

    Article  Google Scholar 

  69. Haro JM, Suarez D, Novick D, et al. Three-year antipsychotic effectiveness in the outpatient care of schizophrenia: observational versus randomized studies results. Eur Neuropsychopharmacol 2007 Mar; 17(4): 235–44

    Article  PubMed  CAS  Google Scholar 

  70. Zyprexa® (olanzapine) [US prescribing information]. Indianapolis (IN): Eli Lilly and Company, 2009 [online]. Available from URL: http://pi.lilly.com/us/zyprexa-pi.pdf [Accessed 2010 May 28]

  71. McIntyre RS, Trakas K, Lin D, et al. Risk of weight gain associated with antipsychotic treatment: results from the Canadian National Outcomes Measurement Study in Schizophrenia. Can J Psychiatry 2003 Nov; 48(10): 689–94

    PubMed  Google Scholar 

  72. Lipkovich I, Jacobson JG, Hardy TA, et al. Early evaluation of patient risk for substantial weight gain during olanzapine treatment for schizophrenia, schizophreniform, or schizoaffective disorder. BMC Psychiatry 2008 Sept; 8: 78

    Article  PubMed  Google Scholar 

  73. Kinon BJ, Basson BR, Gilmore JA, et al. Long-term olanzapine treatment: weight change and weight-related health factors in schizophrenia. J Clin Psychiatry 2001 Feb; 62(2): 92–100

    Article  PubMed  CAS  Google Scholar 

  74. Basson BR, Kinon BJ, Taylor CC, et al. Factors influencing acute weight change in patients with schizophrenia treated with olanzapine, haloperidol, or risperidone. J Clin Psychiatry 2001 Apr; 62(4): 231–8

    Article  PubMed  CAS  Google Scholar 

  75. Ascher-Svanum H, Stensland MD, Kinon BJ, et al. Weight gain as a prognostic indicator of therapeutic improvement during acute treatment of schizophrenia with placebo or active antipsychotic. J Psychopharmacol 2005 Nov; 19(6 Suppl.): 110–7

    Article  PubMed  Google Scholar 

  76. Czobor P, Volavka J, Sheitman B, et al. Antipsychoticinduced weight gain and therapeutic response: a differential association. J Clin Psychopharmacol 2002 Jun; 22(3): 244–51

    Article  PubMed  CAS  Google Scholar 

  77. Bustillo JR, Buchanan RW, Irish D, et al. Differential effect of clozapine on weight: a controlled study. Am J Psychiatry 1996 Jun; 153(6): 817–9

    PubMed  CAS  Google Scholar 

  78. Hennen J, Perlis RH, Sachs G, et al. Weight gain during treatment of bipolar I patients with olanzapine. J Clin Psychiatry 2004 Dec; 65(12): 1679–87

    Article  PubMed  CAS  Google Scholar 

  79. Russell JM, Mackell JA. Bodyweight gain associated with atypical antipsychotics: epidemiology and therapeutic implications. CNS Drugs 2001; 15(7): 537–51

    Article  PubMed  CAS  Google Scholar 

  80. Lipkovich I, Citrome L, Perlis R, et al. Early predictors of substantial weight gain in bipolar patients treated with olanzapine. J Clin Psychopharmacol 2006 Jun; 26(3): 316–20

    Article  PubMed  CAS  Google Scholar 

  81. Ahmed S, Lipkovich I, Ahl J, et al. Early identification of patients at risk for substantial weight gain during treatment of psychotic disorders [abstract]. 31st Annual Meeting of the North American Primary Care Research Group (NAPCRG); 2003 Oct 25–28; Banff, Alberta, Canada, 2003

  82. Reynolds GP, Hill MJ, Kirk SL. The 5-HT2C receptor and antipsychotic induced weight gain-mechanisms and genetics. J Psychopharmacol 2006 Jul; 20(4 Suppl.): 15–8

    Article  PubMed  Google Scholar 

  83. Reynolds GP, Zhang ZJ, Zhang XB. Association of antipsychotic drug-induced weight gain with a 5-HT2C receptor gene polymorphism. Lancet 2002 Jun 15; 359(9323): 2086–7

    Article  PubMed  CAS  Google Scholar 

  84. Lencz T, Malhotra AK. Pharmacogenetics of antipsychoticinduced side effects. Dialogues Clin Neurosci 2009; 11(4): 405–15

    PubMed  Google Scholar 

  85. Ujike H, Nomura A, Morita Y, et al. Multiple genetic factors in olanzapine-induced weight gain in schizophrenia patients: a cohort study. J Clin Psychiatry 2008 Sep; 69(9): 1416–22

    Article  PubMed  CAS  Google Scholar 

  86. Bishop JR, Ellingrod VL, Moline J, et al. Pharmacogenetics of antipsychotic-induced weight gain. Med Sci Monit 2006; 12(2): BR47–50

    PubMed  CAS  Google Scholar 

  87. Müller DJ, Kennedy JL. Genetics of antipsychotic treatment emergent weight gain in schizophrenia. Pharmacogenomics 2006 Sep; 7(6): 863–87

    Article  PubMed  Google Scholar 

  88. Citrome L. Olanzapine: interpreting the label change. Int J Clin Pract 2007 Dec; 61(12): 1960–2

    Article  PubMed  CAS  Google Scholar 

  89. McEvoy JP, Meyer JM, Goff DC, et al. Prevalence of the metabolic syndrome in patients with schizophrenia: baseline results from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial and comparison with national estimates from NHANES III. Schizophr Res 2005 Dec; 80(1): 19–32

    Article  PubMed  Google Scholar 

  90. Mokdad AH, Ford ES, Bowman BA, et al. The continuing increase of diabetes in the US [letter]. Diabetes Care 2001 Feb; 24(2): 412

    Article  PubMed  CAS  Google Scholar 

  91. Barrett TB, Serre P. Blood analysis and sugar tolerance in mental disease. J Nerv Ment Dis 1924 Jun; 59(6): 561–70

    Article  CAS  Google Scholar 

  92. Drury KK, Farron-Ridge C. Some observations of the types of blood-sugar curves found in different forms of insanity. J Ment Sci 1921; 71: 8–29

    Google Scholar 

  93. Henry GW, Mangam E. Blood in personality disorders: biochemical studies. Arch Neurol Psychiatry 1925; 13(6): 743–9

    Article  CAS  Google Scholar 

  94. Kasanin J. The blood sugar curve in mental disease, II: the schizophrenia (dementia praecox) groups. Arch Neurol Psychiatry 1926 Oct; 16(4): 414–9

    Article  Google Scholar 

  95. Kooy FH. Hyperglycemia in mental disorders. Brain 1919; 42: 214–89

    Article  CAS  Google Scholar 

  96. Lorenz WF. Sugar tolerance in dementia praecox and other mental disorders. Arch Neurol Psychiatry 1922 Aug; 8(2): 184–96

    Article  CAS  Google Scholar 

  97. Raphael T, Parsons JP. Blood sugar studies in dementia praecox and manic-depressive insanity. Arch Neurol Psychiatry 1921 Jun; 5(6): 687–709

    Article  CAS  Google Scholar 

  98. Citrome L, Jaffe A, Levine J, et al. Incidence, prevalence, and surveillance for diabetes in New York State psychiatric hospitals, 1997–2004. Psychiatr Serv 2006 Aug; 57(8): 1132–9

    Article  PubMed  Google Scholar 

  99. Centers for Disease Control and Prevention. Crude and age-adjusted incidence of diagnosed diabetes per 1,000 population aged 18–79 years, United States, 1980–2007: Feb 2009 [online]. Available from: URL: http://www.cdc.gov/diabetes/statistics/incidence/fig2.htm [Accessed 2010 Apr 22]

  100. Cassidy F, Ahearn E, Carroll BJ. Elevated frequency of diabetes mellitus in hospitalized manic-depressive patients. Am J Psychiatry 1999 Sep; 156(9): 1417–20

    PubMed  CAS  Google Scholar 

  101. Regenold WT, Thapar RK, Marano C, et al. Increased prevalence of type 2 diabetes mellitus among psychiatric inpatients with bipolar I affective and schizoaffective disorders independent of psychotropic drug use. J Affect Disord 2002 Jun; 70(1): 19–26

    Article  PubMed  Google Scholar 

  102. Gough SC, O’Donovan MC. Clustering of metabolic comorbidity in schizophrenia: a genetic contribution? J Psychopharmacol 2005 Nov; 19(6 Suppl.): 47–55

    Article  PubMed  Google Scholar 

  103. Barker DJ, Hales CN, Fall CH, et al. Type 2 (non-insulindependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth. Diabetologia 1993 Jan; 36(1): 62–7

    Article  PubMed  CAS  Google Scholar 

  104. Susser E, Neugebauer R, Hoek HW, et al. Schizophrenia after prenatal famine: further evidence. Arch Gen Psychiatry 1996 Jan; 53(1): 25–31

    Article  PubMed  CAS  Google Scholar 

  105. Brown S, Birtwistle J, Roe L, et al. The unhealthy lifestyle of people with schizophrenia. Psychol Med 1999 May; 29(3): 697–701

    Article  PubMed  CAS  Google Scholar 

  106. Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Canadian Diabetes Association 2008 clinical practice guidelines for the prevention and management of diabetes in Canada. Can J Diabetes 2008 Sep; 32Suppl. 1: S1–201

    Google Scholar 

  107. Woo V, Harris SB, Houlden RL. Canadian Diabetes Association position paper on antipsychotic medications and associated risk of weight gain and diabetes. Can J Diabetes 2005 Jun; 29(2): 111–2

    Google Scholar 

  108. Ryan MC, Collins P, Thakore JH. Impaired fasting glucose tolerance in first-episode, drug-naive patients with schizophrenia. Am J Psychiatry 2003 Feb; 160(2): 284–9

    Article  PubMed  Google Scholar 

  109. Spelman LM, Walsh PI, Sharifi N, et al. Impaired glucose tolerance in first-episode drug-naive patients with schizophrenia. Diabet Med 2007 May; 24(5): 481–5

    Article  PubMed  CAS  Google Scholar 

  110. Dinan TG. Stress and the genesis of diabetes mellitus in schizophrenia. Br J Psychiatry 2004 Apr; 184Suppl. 47: S72–5

    Article  Google Scholar 

  111. Zhang ZJ, Yao ZJ, Liu W, et al. Effects of antipsychotics on fat deposition and changes in leptin and insulin levels: magnetic resonance imaging study of previously untreated people with schizophrenia. Br J Psychiatry 2004 Jan; 184: 58–62

    Article  PubMed  Google Scholar 

  112. Arranz B, Rosel P, Ramírez N, et al. Insulin resistance and increased leptin concentrations in noncompliant schizophrenia patients but not in antipsychotic-naive firstepisode schizophrenia patients. J Clin Psychiatry 2004 Oct; 65(10): 1335–42

    Article  PubMed  CAS  Google Scholar 

  113. Saddichha S, Manjunatha N, Ameen S, et al. Metabolic syndrome in first episode schizophrenia: a randomized double-blind controlled, short-term prospective study. Schizophr Res 2008 Apr; 101(1–3): 266–72

    Article  PubMed  Google Scholar 

  114. Citrome LL, Holt RI, Zachry WM, et al. Risk of treatmentemergent diabetes mellitus in patients receiving antipsychotics. Ann Pharmacother 2007 Oct; 41(10): 1593–603

    Article  PubMed  CAS  Google Scholar 

  115. Holt RI, Abdelrahman T, Hirsch M, et al. The prevalence of undiagnosed metabolic abnormalities in people with serious mental illness. J Psychopharmacol 2010 Jun; 24(6): 867–73

    Article  PubMed  CAS  Google Scholar 

  116. Jin H, Meyer JM, Jeste DV. Phenomenology of and risk factors for new-onset diabetes mellitus and diabetic ketoacidosis associated with atypical antipsychotics: an analysis of 45 published cases. Ann Clin Psychiatry 2002 Mar; 14(1): 59–64

    PubMed  Google Scholar 

  117. Sowell M, Mukhopadhyay N, Cavazzoni P, et al. Evaluation of insulin sensitivity in healthy volunteers treated with olanzapine, risperidone, or placebo: a prospective, randomized study using the two-step hyperinsulinemic, euglycemic clamp. J Clin Endocrinol Metab 2003 Dec; 88(12): 5875–80

    Article  PubMed  CAS  Google Scholar 

  118. Sowell MO, Mukhopadhyay N, Cavazzoni P, et al. Hyperglycemic clamp assessment of insulin secretory responses in normal subjects treated with olanzapine, risperidone, or placebo. J Clin Endocrinol Metab 2002 Jun; 87(6): 2918–23

    Article  PubMed  CAS  Google Scholar 

  119. Colditz GA, Willett WC, Rotnitzky A, et al. Weight gain as a risk factor for clinical diabetes mellitus in women. Ann Intern Med 1995 Apr; 122(7): 481–6

    PubMed  CAS  Google Scholar 

  120. Engl J, Laimer M, Niederwanger A, et al. Olanzapine impairs glycogen synthesis and insulin signaling in L6 skeletal muscle cells. Mol Psychiatry 2005 Dec; 10(12): 1089–96

    Article  PubMed  CAS  Google Scholar 

  121. Ader M, Kim SP, Catalano KJ, et al. Metabolic dysregulation with atypical antipsychotics occurs in the absence of underlying disease: a placebo-controlled study of olanzapine and risperidone in dogs. Diabetes 2005 Mar; 54(3): 862–71

    Article  PubMed  CAS  Google Scholar 

  122. Baptista T, Alvarez L, Lacruz A, et al. Glucose tolerance and serum insulin levels in an animal model of obesity induced by sub-acute or chronic administration of antipsychotic drugs. Prog Neuropsychopharmacol Biol Psychiatry 1999 Feb; 23(2): 277–87

    Article  PubMed  CAS  Google Scholar 

  123. Melkersson K. Clozapine and olanzapine, but not conventional antipsychotics, increase insulin release in vitro. Eur Neuropsychopharmacol 2004 Mar; 14(2): 115–9

    Article  PubMed  CAS  Google Scholar 

  124. Melkersson K, Jansson E. The atypical antipsychotics quetiapine, risperidone and ziprasidone do not increase insulin release in vitro. Neuro Endocrinol Lett 2005 Jun; 26(3): 205–8

    PubMed  CAS  Google Scholar 

  125. Cohen D, Batstra MR, Gispen-de Wied CC. Immunological characteristics of diabetes in schizophrenia. Diabetologia 2005 Sep; 48(9): 1941–2

    Article  PubMed  Google Scholar 

  126. Reaven GM, Lieberman JA, Sethuraman G, et al. In search of moderators and mediators of hyperglycemia with atypical antipsychotic treatment. J Psychiatr Res 2009 July; 43(11): 997–1002

    Article  PubMed  Google Scholar 

  127. Bushe C, Paton C. The potential impact of antipsychotics on lipids in schizophrenia: is there enough evidence to confirm a link? J Psychopharmacol 2005 Nov; 19(6 Suppl.): 76–83

    Article  PubMed  Google Scholar 

  128. Fernø J, Raeder MB, Vik-Mo AO, et al. Antipsychotic drugs activate SREBP-regulated expression of lipid biosynthetic genes in cultured human glioma cells: a novel mechanism of action? Pharmacogenomics J 2005; 5(5): 298–304

    Article  PubMed  CAS  Google Scholar 

  129. Fernø J, Skrede S, Vik-Mo AO, et al. Drug-induced activation of SREBP-controlled lipogenic gene expression in CNS-related cell lines: marked differences between various antipsychotic drugs. BMC Neurosci 2006 Oct; 7: 69

    Article  PubMed  CAS  Google Scholar 

  130. Raeder MB, Fernø J, Vik-Mo AO, et al. SREBP activation by antipsychotic- and antidepressant-drugs in cultured human liver cells: relevance for metabolic side-effects. Mol Cell Biochem 2006 Sep; 289(1–2): 167–73

    Article  PubMed  CAS  Google Scholar 

  131. Koro CE, Fedder DO, L’Italien GJ, et al. An assessment of the independent effects of olanzapine and risperidone exposure on the risk of hyperlipidemia in schizophrenic patients. Arch Gen Psychiatry 2002 Nov; 59(11): 1021–6

    Article  PubMed  CAS  Google Scholar 

  132. Atmaca M, Kuloglu M, Tezcan E, et al. Serum leptin and triglyceride levels in patients on treatment with atypical antipsychotics. J Clin Psychiatry 2003 May; 64(5): 598–604

    Article  PubMed  CAS  Google Scholar 

  133. Conley RR, Mahmoud R. A randomized double-blind study of risperidone and olanzapine in the treatment of schizophrenia or schizoaffective disorder. Am J Psychiatry 2001 May; 158(5): 765–74

    Article  PubMed  CAS  Google Scholar 

  134. Meyer JM, Davis VG, McEvoy JP, et al. Impact of antipsychotic treatment on nonfasting triglycerides in the CATIE Schizophrenia Trial phase 1. Schizophr Res 2008 Aug; 103(1–3): 104–9

    Article  PubMed  Google Scholar 

  135. Tiihonen J, Wahlbeck K, Lonnqvist J, et al. Effectiveness of antipsychotic treatments in a nationwide cohort of patients in community care after first hospitalisation due to schizophrenia and schizoaffective disorder: observational follow-up study. BMJ 2006 Jul; 333(7561): 224–7

    Article  PubMed  Google Scholar 

  136. Tiihonen J, Lonnqvist J, Wahlbeck K, et al. 11-year followup of mortality in patients with schizophrenia: a population-based cohort study (FIN1 1 study). Lancet 2009 Aug; 374(9690): 620–7

    Article  PubMed  Google Scholar 

  137. Osborn DP, Levy G, Nazareth I, et al. Relative risk of cardiovascular and cancer mortality in people with severe mental illness from the United Kingdom’s General Practice Research Database. Arch Gen Psychiatry 2007 Feb; 64(2): 242–9

    Article  PubMed  Google Scholar 

  138. Ghaemi SN, Thommi S. Death by confounding: bias and mortality. Int J Clin Pract. 2010 Jul; 64(8): 1009–14

    Article  PubMed  CAS  Google Scholar 

  139. Bushe C, Holt R. Prevalence of diabetes and impaired glucose tolerance in patients with schizophrenia. Br J Psychiatry Suppl 2004 Apr; 184(47): S67–71

    Article  Google Scholar 

  140. Goff DC, Sullivan LM, McEvoy JP, et al. A comparison of ten-year cardiac risk estimates in schizophrenia patients from the CATIE study and matched controls. Schizophr Res 2005 Dec; 80(1): 45–53

    Article  PubMed  Google Scholar 

  141. Citrome L. Metabolic syndrome and cardiovascular disease. J Psychopharmacol 2005 Nov; 19(6 Suppl.): 84–93

    Article  PubMed  Google Scholar 

  142. Citrome L, Yeomans D. Do guidelines for severe mental illness promote physical health and well-being? J Psychopharmacol 2005 Nov; 19(6 Suppl): 102–9

    Article  PubMed  Google Scholar 

  143. De Hert M, van Eyck D, De Nayer A. Metabolic abnormalities associated with second generation antipsychotics: fact or fiction? Development of guidelines for screening and monitoring. Int Clin Psychopharmacol 2006 Mar; 21Suppl 2: S11–5

    Article  PubMed  Google Scholar 

  144. Expert Group. ’schizophrenia and Diabetes 2003’ Expert Consensus Meeting, Dublin, 3–4 October 2003: consensus summary. Br J Psychiatry 2004 1; 84Suppl. 47: S112–4

    Google Scholar 

  145. De Nayer A, De Hert M, Scheen A, et al. Belgian consensus on metabolic problems associated with atypical antipsychotics. Int J Psychiatry Clin Pract 2005; 9(2): 130–7

    Article  Google Scholar 

  146. American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, et al. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care 2004 Feb; 27(2): 596–601

    Article  Google Scholar 

  147. De Hert M, Dekker JM, Wood D, 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 2009 Sep; 24(6): 412–24

    Article  PubMed  Google Scholar 

  148. Smith S, Yeomans D, Bushe CJ, et al. A well-being programme in severe mental illness: reducing risk for physical ill-health — a post-programme service evaluation at 2 years. Eur Psychiatry 2007 Oct; 22(7): 413–8

    Article  PubMed  Google Scholar 

  149. Vreeland B, Minsky S, Gara MA, et al. Solutions for wellness: results of a manualized psychoeducational program for adults with psychiatric disorders. Am J Psychiatr Rehabil 2010 Jan; 13(1): 55–72

    Article  Google Scholar 

  150. Citrome L, Vreeland B. Schizophrenia, obesity, and antipsychotic medications: what can we do. Postgrad Med 2008 Jul; 120(2): 18–33

    Article  PubMed  Google Scholar 

  151. Holt RIG, Pendlebury J, Wildgust HJ, et al. Intentional weight loss in overweight and obese patients with severe mental illness: 8-year experience of a behavioral treatment program. J Clin Psychiatry 2010 Jun; 71(6): 800–5

    Article  PubMed  Google Scholar 

  152. Meyer JM, Davis VG, Goff DC, et al. Change in metabolic syndrome parameters with antipsychotic treatment in the CATIE Schizophrenia Trial: prospective data from phase 1. Schizophr Res 2008 Apr; 101(1–3): 273–86

    Article  PubMed  Google Scholar 

  153. Agid O, Kapur S, Arenovich T, et al. Delayed-onset hypothesis of antipsychotic action: a hypothesis tested and rejected. Arch Gen Psychiatry 2003 Dec; 60(12): 1228–35

    Article  PubMed  CAS  Google Scholar 

  154. Agid O, Seeman P, Kapur S. The “delayed onset” of antipsychotic action: an idea whose time has come and gone. J Psychiatry Neurosci 2006 Mar; 31(2): 93–100

    PubMed  Google Scholar 

  155. Kinon BJ, Kaiser CJ, Ahmed S, et al. Association between early and rapid weight gain and change in weight over one year of olanzapine therapy in patients with schizophrenia and related disorders. J Clin Psychopharmacol 2005 Jun; 25(3): 255–8

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The preparation of this article was funded by Eli Lilly and Company (Indianapolis, IN, USA).

The authors acknowledge Ruth Williams, Luke Molloy, Anna Mett, Ray Hill, Joanne Dalton, Claire Byrne, Stephanie Blick and Max Chang of Wolters Kluwer Pharma Solutions for technical writing assistance and Angela Lorio and Joseph Durrant of i3 Statprobe for editorial assistance.

Leslie Citrome is a consultant for, has received honoraria from or has conducted clinical research supported by the following: Abbott Laboratories, AstraZeneca Pharmaceuticals, Avanir Pharmaceuticals, Azur Pharma Inc, Barr Laboratories, Bristol-Myers Squibb (BMS), Eli Lilly and Company, Forest Research Institute, GlaxoSmithKline (GSK), Janssen Pharmaceuticals, Jazz Pharmaceuticals, Merck, Novartis, Pfizer Inc, Sunovion, Valeant Pharmaceuticals and Vanda Pharmaceuticals. Dr Citrome also holds stock in Abbott Laboratories, BMS, Eli Lilly and Company, Johnson & Johnson, Merck and Pfizer.

Richard Holt has undertaken lectures for AstraZeneca Pharmaceuticals, Eli Lilly and Company, GSK, Merck Sharp and Dohme (MSD), BMS and Novo Nordisk. He has served on advisory boards for AstraZeneca, BMS, Eli Lilly and Company, GSK, MSD and Novo Nordisk. He has received funding to attend conferences from Astra Zeneca, Eli Lilly and Company, GSK and Novo Nordisk.

Vicki Poole Hoffmann and Daniel Walker are employees of Eli Lilly and Company.

Author information

Authors and Affiliations

  1. Department of Psychiatry, New York University School of Medicine, New York, USA

    Leslie Citrome MD, MPH

  2. Developmental Origins of Health and Disease Division, School of Medicine, University of Southampton, Southampton, UK

    Richard I. G. Holt

  3. Eli Lilly and Company, Indianapolis, Indiana, USA

    Daniel J. Walker & Vicki Poole Hoffmann

Authors
  1. Leslie Citrome MD, MPH
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Richard I. G. Holt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daniel J. Walker
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vicki Poole Hoffmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Leslie Citrome MD, MPH.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Citrome, L., Holt, R.I.G., Walker, D.J. et al. Weight Gain and Changes in Metabolic Variables following Olanzapine Treatment in Schizophrenia and Bipolar Disorder. Clin. Drug Investig. 31, 455–482 (2011). https://doi.org/10.2165/11589060-000000000-00000

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/11589060-000000000-00000

Keywords

Search

Navigation