Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
CNS Drugs
Published in: CNS Drugs 7/2008

01-07-2008 | Review Article

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

A Systematic Critical Reappraisal

Authors: Dr Mario Álvarez-Jiménez, César González-Blanch, Benedicto Crespo-Facorro, Sarah Hetrick, Jose Manuel Rodriguez-Sánchez, Rocio Pérez-Iglesias, Jose Luis

Published in: CNS Drugs | Issue 7/2008

Login to get access

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.
Literature
1.
Green AI, Patel JK, Goisman RM, et al. Weight gain from novel antipsychotic drugs: need for action. Gen Hosp Psychiatry 2000; 22(4): 224–35PubMedCrossRef
2.
Wirshing DA. Schizophrenia and obesity: impact of antipsychotic medications. J Clin Psychiatry 2004; 65Suppl. 18: 13–26PubMed
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): 179–83PubMed
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): 565–7PubMedCrossRef
5.
Sussman N. Review of atypical antipsychotics and weight gain. J Clin Psychiatry 2001; 62Suppl. 23: 5–12PubMed
6.
Aronne LJ. Epidemiology, morbidity, and treatment of overweight and obesity. J Clin Psychiatry 2001; 62Suppl. 23: 13–22PubMed
7.
Crisp AH, Gelder MG, Rix S, et al. Stigmatisation of people with mental illnesses. Br J Psychiatry 2000; 177: 4–7PubMedCrossRef
8.
Weiden PJ, Mackell JA, McDonnell DD. Obesity as a risk factor for antipsychotic noncompliance. Schizophr Res 2004; 66(1): 51–7PubMedCrossRef
9.
Angermeyer MC, Matschisger H. Neuroleptics and quality of life: a patient survey. Psychiatr Prax 2000; 27: 64–8PubMed
10.
Marder SR, Essock SM, Miller AL, et al. Physical health monitoring of patients with schizophrenia. Am J Psychiatry 2004; 161(8): 1334–49PubMedCrossRef
11.
McCreadie RG. Diet, smoking and cardiovascular risk in people with schizophrenia: a descriptive study. Br J Psychiatry 2003; 183: 534–9PubMedCrossRef
12.
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): 1253–60PubMedCrossRef
15.
Addington J, Mansley C, Addington D. Weight gain in first episode psychosis. Can J Psychiatry 2003; 48: 272–176PubMed
16.
Coldham EL, Addington J, Addington D. Medication adherence of individuals with a first episode of psychosis. Acta Psychiatr Scand 2002; 106(4): 286–90PubMedCrossRef
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): 341–6PubMedCrossRef
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): 1008–12PubMedCrossRef
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): 118–23PubMedCrossRef
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): 1733–40PubMedCrossRef
21.
Allison DB, Mentore JL, Heo M, et al. Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry 1999; 156: 1686–96PubMed
22.
Starfield B. Quality-of-care research: internal elegance and external relevance. JAMA 1998; 280(11): 1006–8PubMedCrossRef
23.
American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association, 1994
24.
World Health Organization. International classification of diseases. 10th ed. Geneva: World Health Organization, 1992
25.
Allison DB, Cassey DE. Antipsychotic-induced weight gain: a review of the literature. J Clin Psychiatry 2001; 62 Suppl. 7: 22–31
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): 1624–33PubMedCrossRef
27.
Apiquian R, Fresan A, Ulloa RE, et al. Amoxapine as an atypical antipsychotic: a comparative study vs risperidone. Neuropsychopharmacology 2005; 30(12): 2236–44PubMedCrossRef
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
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: 3PubMedCrossRef
30.
Baymiller SP, Ball P, McMahon RP, et al. Weight and blood pressure change during clozapine treatment. Clin Neuropharmacol 2002; 25(4): 202–6PubMedCrossRef
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): 173–80PubMedCrossRef
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): 1879–87PubMedCrossRef
33.
Buchanan RW, Ball MP, Weiner E, et al. Olanzapine treatment of residual positive and negative symptoms. Am J Psychiatry 2005; 162(1): 124–9PubMedCrossRef
34.
Buckley PF, Goldstein JM, Emsley RA. Efficacy and tolerability of quetiapine in poorly responsive, chronic schizophrenia. Schizophr Res 2004; 66(2–3): 143–50PubMedCrossRef
35.
Bustillo JR, Buchanan RW, Irish D, et al. Differential effect of clozapine on weight: a controlled study. Am J Psychiatry 1996; 153(6): 817–9PubMed
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): 29–36PubMedCrossRef
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): 765–74PubMedCrossRef
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): 244–51PubMedCrossRef
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): 311–8PubMedCrossRef
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): 279–85PubMedCrossRef
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): 516–23PubMedCrossRef
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): 811–6PubMed
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: 30–6PubMed
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): 763–71PubMedCrossRef
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): 1125–32PubMedCrossRef
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): 181–6PubMed
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): 368–79PubMedCrossRef
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): 355–62PubMedCrossRef
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
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): 63–9PubMedCrossRef
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
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): 254–65PubMedCrossRef
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): 681–90PubMedCrossRef
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
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): 1535–8PubMedCrossRef
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): 1837–47PubMedCrossRef
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): 52–63PubMedCrossRef
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): 1093–103PubMedCrossRef
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): 238–49PubMedCrossRef
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): 259–66CrossRef
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): 16–22PubMedCrossRef
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): 831–8PubMedCrossRef
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): 175–82CrossRef
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
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): 1209–23PubMedCrossRef
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: 563–5CrossRef
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): 1050–60PubMedCrossRef
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): 2096–102PubMedCrossRef
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): 947–53PubMedCrossRef
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): 341–6PubMedCrossRef
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: 537–43PubMedCrossRef
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: 13–22PubMedCrossRef
73.
Addington J, Saeedi H, Addington D. Weight gain in first episode psychosis over three years. Schizophr Res 2006; 81(1–3): 335–6CrossRef
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): 611–22PubMedCrossRef
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): 157–62PubMedCrossRef
76.
Chagnon YC. Susceptibility genes for the side effect of antipsychotics on body weight and obesity. Current Drug Targets 2006 Dec; 7(12): 1681–95PubMedCrossRef
Metadata
Title
Antipsychotic-Induced Weight Gain in Chronic and First-Episode Psychotic Disorders
A Systematic Critical Reappraisal
Authors
Dr Mario Álvarez-Jiménez
César González-Blanch
Benedicto Crespo-Facorro
Sarah Hetrick
Jose Manuel Rodriguez-Sánchez
Rocio Pérez-Iglesias
Jose Luis
Publication date
01-07-2008
Publisher
Springer International Publishing
Published in
CNS Drugs / Issue 7/2008
Print ISSN: 1172-7047
Electronic ISSN: 1179-1934
DOI
https://doi.org/10.2165/00023210-200822070-00002

Other articles of this Issue 7/2008

CNS Drugs 7/2008 Go to the issue

Review Article

Impact of Newer Pharmacological Treatments on Quality of Life in Patients with Parkinson’s Disease

Original Research Article

Effect of Switching Drug Formulations from Immediate-Release to Extended-Release OROS Methylphenidate

Original Research Article

Efficacy and Tolerability of Milnacipran in the Treatment of Major Depression in Comparison with Other Antidepressants

Therapy In Practice

Pathological Laughing and Crying

Adis Spotlight

Spotlight on Bupropion in Major Depressive Disorder