Skip to main content
SpringerLink
Log in

Antipsychotic-Induced Weight Gain in Chronic and First-Episode Psychotic Disorders

A Systematic Critical Reappraisal

  • Review Article
  • Published:
CNS Drugs Aims and scope Submit manuscript

Abstract

Antipsychotic-induced weight gain is an important issue in the treatment of psychotic illnesses, and affects 80% of individuals being treated with antipsychotic drugs. However, the true dimension of weight gain and many accepted ‘facts’ in this area remain unclear as most research has been conducted in short-term trials and has included individuals receiving prolonged antipsychotic treatment.

This review aims to systematically and critically review the evidence on weight gain induced by the two leading second-generation antipsychotics (olanzapine and risperidone) and the most widely researched first-generation antipsychotic (haloperidol) in patients with chronic and first-episode psychotic disorders.

Weight gain was 3- to 4-fold greater in studies that included young patients with limited previous exposure to antipsychotic agents in both short-term studies (7.1–9.2 kg for olanzapine, 4.0–5.6 kg for risperidone and 2.6–3.8 kg for haloperidol vs 1.8–5.4 kg, 1.0–2.3 kg and 0.01–1.4 kg, respectively, in studies that included patients with chronic psychotic disorders) and long-term trials (10.2–15.4 kg for olanzapine, 6.6–8.9 kg for risperidone and 4.0–9.7 kg for haloperidol vs 2.0–6.2 kg, 0.4–3.9 kg and −0.7 to 0.4 kg, respectively). The same disparity was observed regarding the proportion of patients increasing their baseline weight by ≥7% (the cut-off for clinically significant weight gain).

Recent studies carried out in young patients with first-episode psychosis (FEP), along with methodological artefacts in studies of chronic populations, suggest that the magnitude of weight gain reported by much of the literature could in fact be an underestimation of the true magnitude of this adverse effect. Although antipsychotics present idiosyncratic patterns of weight gain, they may also generate similar absolute gains.

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

Fig. 1
Table I
Table II
Table III
Table IV

Similar content being viewed by others

References

  1. Green AI, Patel JK, Goisman RM, et al. Weight gain from novel antipsychotic drugs: need for action. Gen Hosp Psychiatry 2000; 22(4): 224–35

    Article  PubMed  CAS  Google Scholar 

  2. Wirshing DA. Schizophrenia and obesity: impact of antipsychotic medications. J Clin Psychiatry 2004; 65Suppl. 18: 13–26

    PubMed  Google Scholar 

  3. Rumpel C, Ingram DD, Harris TB, et al. The association between weight change and psychological well-being in women. Int J Obes Relat Metab Disord 1994; 18(3): 179–83

    PubMed  CAS  Google Scholar 

  4. Allison DB, Mackell JA, McDonnell DD. The impact of weight gain on quality of life among persons with schizophrenia. Psychiatr Serv 2003; 54(4): 565–7

    Article  PubMed  Google Scholar 

  5. Sussman N. Review of atypical antipsychotics and weight gain. J Clin Psychiatry 2001; 62Suppl. 23: 5–12

    PubMed  CAS  Google Scholar 

  6. Aronne LJ. Epidemiology, morbidity, and treatment of overweight and obesity. J Clin Psychiatry 2001; 62Suppl. 23: 13–22

    PubMed  CAS  Google Scholar 

  7. Crisp AH, Gelder MG, Rix S, et al. Stigmatisation of people with mental illnesses. Br J Psychiatry 2000; 177: 4–7

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  9. Angermeyer MC, Matschisger H. Neuroleptics and quality of life: a patient survey. Psychiatr Prax 2000; 27: 64–8

    PubMed  CAS  Google Scholar 

  10. Marder SR, Essock SM, Miller AL, et al. Physical health monitoring of patients with schizophrenia. Am J Psychiatry 2004; 161(8): 1334–49

    Article  PubMed  Google Scholar 

  11. McCreadie RG. Diet, smoking and cardiovascular risk in people with schizophrenia: a descriptive study. Br J Psychiatry 2003; 183: 534–9

    Article  PubMed  CAS  Google Scholar 

  12. Thakore JH. Metabolic syndrome and schizophrenia. Br J Psychiatry 2005; 186: 455–6

    Article  PubMed  Google Scholar 

  13. Alvarez-Jimenez M, Hetrick SE, González-Blanch, et al. Non-pharmacological management of antipsychotic-induced weight gain: a systematic review and meta-analysis of randomized controlled trials. Br J Psychiatry. In press

  14. Alvarez-Jimenez M, Gonzalez-Blanch C, Vazquez-Barquero JL, et al. Attenuation of antipsychotic-induced weight gain with early behavioral intervention in drug-naive first-episode psychosis patients: a randomized controlled trial. J Clin Psychiatry 2006; 67(8): 1253–60

    Article  PubMed  Google Scholar 

  15. Addington J, Mansley C, Addington D. Weight gain in first episode psychosis. Can J Psychiatry 2003; 48: 272–176

    PubMed  Google Scholar 

  16. Coldham EL, Addington J, Addington D. Medication adherence of individuals with a first episode of psychosis. Acta Psychiatr Scand 2002; 106(4): 286–90

    Article  PubMed  CAS  Google Scholar 

  17. Van Bruggen J, Tijssen J, Dingemans P, et al. Symptom response and side-effects of olanzapine and risperidone in young adults with recent onset schizophrenia. Int Clin Psychopharmacol 2003; 18(6): 341–6

    Article  PubMed  Google Scholar 

  18. Gortmaker SL, Must A, Perrin JM, et al. Social and economic consequences of overweight in adolescence and young adulthood. N Engl J Med 1993; 329(14): 1008–12

    Article  PubMed  CAS  Google Scholar 

  19. Graham KA, Perkins DO, Edwards LJ, et al. Effect of olanzapine on body composition and energy expenditure in adults with first-episode psychosis. Am J Psychiatry 2005; 162(1): 118–23

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  21. Allison DB, Mentore JL, Heo M, et al. Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry 1999; 156: 1686–96

    PubMed  CAS  Google Scholar 

  22. Starfield B. Quality-of-care research: internal elegance and external relevance. JAMA 1998; 280(11): 1006–8

    Article  PubMed  CAS  Google Scholar 

  23. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association, 1994

    Google Scholar 

  24. World Health Organization. International classification of diseases. 10th ed. Geneva: World Health Organization, 1992

    Google Scholar 

  25. Allison DB, Cassey DE. Antipsychotic-induced weight gain: a review of the literature. J Clin Psychiatry 2001; 62 Suppl. 7: 22–31

    Google Scholar 

  26. Addington DE, Pantelis C, Dineen M, et al. Efficacy and tolerability of ziprasidone versus risperidone in patients with acute exacerbation of schizophrenia or schizoaffective disorder: an 8-week, double-blind, multicenter trial. J Clin Psychiatry 2004; 65(12): 1624–33

    Article  PubMed  CAS  Google Scholar 

  27. Apiquian R, Fresan A, Ulloa RE, et al. Amoxapine as an atypical antipsychotic: a comparative study vs risperidone. Neuropsychopharmacology 2005; 30(12): 2236–44

    Article  PubMed  CAS  Google Scholar 

  28. Arvanitis LA, Miller BG. Multiple fixed doses of “Seroquel” (quetiapine) in patients with acute exacerbation of schizophrenia: a comparison with haloperidol and placebo. The Seroquel Trial 13 Study Group. Biol Psychiatry 1997; 42(4): 233–46

    CAS  Google Scholar 

  29. Ascher-Svanum H, Stensland M, Zhao Z, et al. Acute weight gain, gender, and therapeutic response to antipsychotics in the treatment of patients with schizophrenia. BMC Psychiatry 2005; 5: 3

    Article  PubMed  Google Scholar 

  30. Baymiller SP, Ball P, McMahon RP, et al. Weight and blood pressure change during clozapine treatment. Clin Neuropharmacol 2002; 25(4): 202–6

    Article  PubMed  CAS  Google Scholar 

  31. Bitter I, Dossenbach MR, Brook S, et al. Olanzapine versus clozapine in treatment-resistant or treatment-intolerant schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2004; 28(1): 173–80

    Article  PubMed  CAS  Google Scholar 

  32. 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; 162(10): 1879–87

    Article  PubMed  Google Scholar 

  33. Buchanan RW, Ball MP, Weiner E, et al. Olanzapine treatment of residual positive and negative symptoms. Am J Psychiatry 2005; 162(1): 124–9

    Article  PubMed  Google Scholar 

  34. Buckley PF, Goldstein JM, Emsley RA. Efficacy and tolerability of quetiapine in poorly responsive, chronic schizophrenia. Schizophr Res 2004; 66(2–3): 143–50

    Article  PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  36. Chan HY, Lin WW, Lin SK, et al. Efficacy and safety of aripiprazole in the acute treatment of schizophrenia in Chinese patients with risperidone as an active control: a randomized trial. J Clin Psychiatry 2007; 68(1): 29–36

    Article  PubMed  CAS  Google Scholar 

  37. 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; 158(5): 765–74

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  39. Dossenbach MR, Folnegovic-Smalc V, Hotujac L, et al. Double-blind, randomized comparison of olanzapine versus fluphenazine in the long-term treatment of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2004; 28(2): 311–8

    Article  PubMed  CAS  Google Scholar 

  40. Gattaz WF, Diehl A, Geuppert MS, et al. Olanzapine versus flupenthixol in the treatment of inpatients with schizophrenia: a randomized double-blind trial. Pharmacopsychiatry 2004; 37(6): 279–85

    Article  PubMed  CAS  Google Scholar 

  41. Hirsch SR, Kissling W, Bauml J, et al. A 28-week comparison of ziprasidone and haloperidol in outpatients with stable schizophrenia. J Clin Psychiatry 2002; 63(6): 516–23

    Article  PubMed  CAS  Google Scholar 

  42. Hwang TJ, Lin SK, Lin HN. Efficacy and safety of zotepine for the treatment of Taiwanese schizophrenic patients: a double-blind comparison with haloperidol. J Formos Med Assoc 2001; 100(12): 811–6

    PubMed  CAS  Google Scholar 

  43. Hwang TJ, Lee SM, Sun HJ, et al. Amisulpride versus risperidone in the treatment of schizophrenic patients: a double-blind pilot study in Taiwan. J Formos Med Assoc 2003; 102: 30–6

    PubMed  CAS  Google Scholar 

  44. Kane JM, Carson WH, Saha AR, et al. Efficacy and safety of aripiprazole and haloperidol versus placebo in patients with schizophrenia and schizoaffective disorder. J Clin Psychiatry 2002; 63(9): 763–71

    Article  PubMed  CAS  Google Scholar 

  45. Kane JM, Eerdekens M, Lindenmayer JP, et al. Long-acting injectable risperidone: efficacy and safety of the first long-acting atypical antipsychotic. Am J Psychiatry 2003; 160(6): 1125–32

    Article  PubMed  Google Scholar 

  46. Kelly DL, Conley RR, Richardson CM, et al. Adverse effects and laboratory parameters of high-dose olanzapine vs. clozapine in treatment-resistant schizophrenia. Ann Clin Psychiatry 2003; 15(3–4): 181–6

    PubMed  Google Scholar 

  47. Lindenmayer JP, Khan A, Iskander A, et al. A randomized controlled trial of olanzapine versus haloperidol in the treatment of primary negative symptoms and neurocognitive deficits in schizophrenia. J Clin Psychiatry 2007 Mar; 68(3): 368–79

    Article  PubMed  CAS  Google Scholar 

  48. Martin S, Ljo H, Peuskens J, et al. A double-blind, randomised comparative trial of amisulpride versus olanzapine in the treatment of schizophrenia: short-term results at two months. Curr Med Res Opin 2002; 18(6): 355–62

    Article  PubMed  CAS  Google Scholar 

  49. 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; 65 Suppl. 18: 47–56

    Google Scholar 

  50. Mortimer A, Martin S, Loo H, et al. A double-blind, randomized comparative trial of amisulpride versus olanzapine for 6 months in the treatment of schizophrenia. Int Clin Psychopharmacol 2004; 19(2): 63–9

    Article  PubMed  Google Scholar 

  51. Peuskens J, Bech P, Moller HJ, et al. Amisulpride vs. risperidone in the treatment of acute exacerbations of schizophrenia. Amisulpride Study Group. Psychiatry Res 1999; 88(2): 107–17

    CAS  Google Scholar 

  52. Potkin SG, Gharabawi GM, Greenspan AJ, et al. A double-blind comparison of risperidone, quetiapine and placebo in patients with schizophrenia experiencing an acute exacerbation requiring hospitalization. Schizophr Res 2006; 85(1–3): 254–65

    Article  PubMed  Google Scholar 

  53. Potkin SG, Saha AR, Kujawa MJ, et al. Aripiprazole, an antipsychotic with a novel mechanism of action, and risperidone vs placebo in patients with schizophrenia and schizoaffective disorder. Arch Gen Psychiatry 2003; 60(7): 681–90

    Article  PubMed  CAS  Google Scholar 

  54. Sechter D, Peuskens J, Fleurot O, et al. Amisulpride vs. risperidone in chronic schizophrenia: results of a 6-month double-blind study. Neuropsychopharmacology 2002; 27(6): 1071–81

    CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  56. 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; 161(10): 1837–47

    Article  PubMed  Google Scholar 

  57. Tollefson GD, Birkett MA, Kiesler GM, et al. Double-blind comparison of olanzapine versus clozapine in schizophrenic patients clinically eligible for treatment with clozapine. Biol Psychiatry 2001; 49(1): 52–63

    Article  PubMed  CAS  Google Scholar 

  58. Zhong KX, Sweitzer DE, Hamer RM, et al. Comparison of quetiapine and risperidone in the treatment of schizophrenia: a randomized, double-blind, flexible-dose, 8-week study. J Clin Psychiatry 2006; 67(7): 1093–103

    Article  PubMed  CAS  Google Scholar 

  59. Alvarez E, Ciudad A, Olivares JM, et al. A randomized, 1-year follow-up study of olanzapine and risperidone in the treatment of negative symptoms in outpatients with schizophrenia. J Clin Psychopharmacol 2006; 26(3): 238–49

    Article  PubMed  CAS  Google Scholar 

  60. 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; 189(2): 259–66

    Article  CAS  Google Scholar 

  61. Csernansky JG, Mahmoud R, Brenner R. A comparison of risperidone and haloperidol for the prevention of relapse in patients with schizophrenia. N Engl J Med 2002; 346(1): 16–22

    Article  PubMed  CAS  Google Scholar 

  62. Silva de Lima M, de Jesus Mari J, Breier A, et al. Quality of life in schizophrenia: a multicenter, randomized, naturalistic, controlled trial comparing olanzapine to first-generation antipsychotics. J Clin Psychiatry 2005; 66(7): 831–8

    Article  PubMed  CAS  Google Scholar 

  63. Emsley R, Turner HJ, Schronen J, et al. Effects of quetiapine and haloperidol on body mass index and glycaemic control: a long-term, randomized, controlled trial. Int J Neuropsycho-pharmacol 2005; 8(2): 175–82

    Article  CAS  Google Scholar 

  64. Kasper S, Lerman MN, McQuade RD, et al. Efficacy and safety of aripiprazole vs. haloperidol for long-term maintenance treatment following acute relapse of schizophrenia. Int J Neuropsychopharmacol 2003; 6(4): 325–37

    CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  66. McEvoy JP, Lieberman JA, Stroup TS, et al. Effectiveness of clozapine versus olanzapine, quetiapine and risperidone in patients with chronic schizophrenia who did not repsond to prior atypical antipsychotic treatment. Am J Psychiatry 2006; 163: 563–5

    Article  Google Scholar 

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

    Article  PubMed  Google Scholar 

  68. Robinson DG, Woerner MG, Napolitano B, et al. Randomized comparison of olanzapine versus risperidone for the treatment of first-episode schizophrenia: 4-month outcomes. Am J Psychiatry 2006; 163(12): 2096–102

    Article  PubMed  Google Scholar 

  69. Schooler N, Rabinowitz J, Davidson M, et al. Risperidone and haloperidol in first-episode psychosis: a long-term randomized trial. Am J Psychiatry 2005; 162(5): 947–53

    Article  PubMed  Google Scholar 

  70. van Bruggen J, Tijssen J, Dingemans P, et al. Symptom response and side-effects of olanzapine and risperidone in young adults with recent onset schizophrenia. Int Clin Psychopharmacol 2003; 18(6): 341–6

    Article  PubMed  Google Scholar 

  71. 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; 187: 537–43

    Article  PubMed  Google Scholar 

  72. Perez-Iglesias R, Crespo-Facorro B, Martinez-Garcia O, et al. Weight gain induced by haloperidol, risperidone and olanzapine after 1 year: findings of a randomized clinical trial in a drug-naive population. Schizophr Res 2008; 99: 13–22

    Article  PubMed  Google Scholar 

  73. Addington J, Saeedi H, Addington D. Weight gain in first episode psychosis over three years. Schizophr Res 2006; 81(1–3): 335–6

    Article  Google Scholar 

  74. Stroup TS, Lieberman JA, McEvoy JP, et al. Effectiveness of olanzapine, quetiapine, risperidone, and ziprasidone in patients with chronic schizophrenia following discontinuation of a previous atypical antipsychotic. Am J Psychiatry 2006 Apr; 163(4): 611–22

    Article  PubMed  Google Scholar 

  75. 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 

  76. Chagnon YC. Susceptibility genes for the side effect of antipsychotics on body weight and obesity. Current Drug Targets 2006 Dec; 7(12): 1681–95

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The present study has been funded by a grant from the Marqués de Valdecilla Public Foundation – Marqués de Valdecilla Research Institute (FMV-IFIMAV), Santander, Spain. The authors acknowledge Sara Gook and Joe Buckby of ORYGEN Research Centre, University of Melbourne, for their helpful comments on an earlier draft of this article. The authors have no conflicts of interest that are directly relevant to the content of this review.

Author information

Authors and Affiliations

  1. ORYGEN Research Centre, University of Melbourne, 35 Poplar Road, Parkville, Melbourne, Victoria, 3054, Australia

    Mario Álvarez-Jiménez & Sarah Hetrick

  2. Department of Psychiatry, University Hospital ‘Marqués de Valdecilla’, University of Cantabria School of Medicine, Santander, Spain

    Mario Álvarez-Jiménez, César González-Blanch, Benedicto Crespo-Facorro, Jose Manuel Rodriguez-Sánchez, Rocio Pérez-Iglesias & Jose Luis

Authors
  1. Mario Álvarez-Jiménez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. César González-Blanch
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Benedicto Crespo-Facorro
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sarah Hetrick
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jose Manuel Rodriguez-Sánchez
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rocio Pérez-Iglesias
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jose Luis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mario Álvarez-Jiménez.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Álvarez-Jiménez, M., González-Blanch, C., Crespo-Facorro, B. et al. Antipsychotic-Induced Weight Gain in Chronic and First-Episode Psychotic Disorders. CNS Drugs 22, 547–562 (2008). https://doi.org/10.2165/00023210-200822070-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00023210-200822070-00002

Keywords

Search

Navigation