Hostname: page-component-cd9895bd7-dzt6s Total loading time: 0 Render date: 2024-12-23T00:01:35.091Z Has data issue: false hasContentIssue false

The impact of weight gain associated with atypical antipsychotic use in schizophrenia

Published online by Cambridge University Press:  24 June 2014

Pierre Chue*
Affiliation:
Department of Psychiatry, University of Alberta
Raphael Cheung
Affiliation:
South-western Ontario Medical Education Network Windsor, Faculty of Medicine and Dentistry, University of Western Ontario, Canada
*
Dr P. Chue, 3rd Floor, 9942-108 Street, Edmonton, Alberta T5K 2J5, Canada. Tel: (780) 401 4189; Fax: (780) 425 9317; E-mail: [email protected]

Abstract

Background:

Atypical antipsychotics offer clear advantages in the management of schizophrenia, compared with conventional neuroleptics, but weight gain is a significant adverse effect with some of these agents.

Objective:

To review the literature on weight gain associated with atypical antipsychotic treatment in schizophrenia.

Methods:

Relevant sources were identified from Medline searches to February 2003 using combinations of keywords including ‘schizophrenia’, ‘antipsychotics’, ‘weight gain’, ‘adverse events’, ‘obesity’, and ‘diabetes’.

Results:

Most atypical antipsychotics induce some weight gain, but the magnitude of the effect varies markedly. The greatest increases are seen with clozapine and olanzapine: risperidone has a slight effect, comparable with that of conventional neuroleptics, while ziprasidone and aripiprazole appear from current data to have little effect. In addition, atypical antipsychotics have been associated with metabolic disturbances, particularly glucose dysregulation and dyslipidemia. These effects tend to be more marked with olanzapine and clozapine than with other agents. Weight gain associated with atypical antipsychotics imposes substantial morbidity, in addition to that associated with schizophrenia itself. Furthermore, weight gain can significantly impair patients' quality of life, and leads to non-adherence with treatment. Effective weight management should include the selection of an appropriate atypical antipsychotic and for effective weight management, as well both diet and exercise, formal weight management programs tailored to the needs of schizophrenic patients may be useful, and some patients may benefit from weight-reducing drugs.

Conclusions:

Weight gain associated with atypical antipsychotics is a common problem that requires effective management. The selection of an agent with a low risk of weight gain, such as risperidone or ziprasidone, is central to such management.

Type
Review Article
Copyright
Copyright © 2004 Blackwell Munksgaard

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Tandon, R. Safety and tolerability: how do newer generation ‘atypical’ antipsychotics compare? Psychiatric Q 2002;73: 297311. CrossRefGoogle ScholarPubMed
Basile, VS, Masellis, M, McIntyre, RSet al. Genetic dissection of atypical antipsychotic-induced weight gain: novel preliminary data on the pharmacogenetic puzzle. J Clin Psychiatry 2001;62(Suppl. 23):4566.Google ScholarPubMed
Ackerman, S, Nolan, LJ. Bodyweight gain induced by psychotropic drugs. Incidence, mechanisms and management. CNS Drugs 1998;9: 135151. CrossRefGoogle Scholar
Baptista, T. Body weight gain induced by antipsychotic drugs: mechanisms and management. Acta Psychiatr Scand 1999;100: 316.CrossRefGoogle ScholarPubMed
Baptista, T, Kin N, Beaulieu, Set al. Obesity and related metabolic abnormalities during antipsychotic drug administration: mechanisms, management and research perspectives. Pharmacopsychiatry 2002;35: 205219.CrossRefGoogle ScholarPubMed
Sussman, N. Choosing a typical antipsychotic. Int Clin Psychopharmacol 2002;17(Suppl. 3):S29S33.Google Scholar
Wetterling, T, Müßigbrodt, HE. Weight gain: side effect of atypical neuroleptics? J Clin Psychopharmacol 1999;19: 316321.CrossRefGoogle ScholarPubMed
Ganguli, R. Weight gain associated with antipsychotic drugs. J Clin Psychiatry 1999;60(Suppl. 21):2024.Google ScholarPubMed
Allison, DB, Mentore, JL, Heo, Met al. Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry 1999;156: 16861696.Google ScholarPubMed
Sussman, N. Review of atypical antipsychotics and weight gain. J Clin Psychiatry 2001;62(Suppl. 23):512.Google ScholarPubMed
Wetterling, T. Bodyweight gain with atypical antipsychotics. A comparative review. Drug Safety 2001;24: 5973.CrossRefGoogle ScholarPubMed
Wirshing, DA, Erhart, SM, Pierre, JMet al. Nonextrapyramidal side effects of novel antipsychotics. Curr Opin Psychiatry 2000;13: 4550. CrossRefGoogle Scholar
Green, AI, Patel, JK, Goisman, RMet al. Weight gain from novel antipsychotic drugs: need for action. General Hosp Psychiatry 2000;22: 224235. CrossRefGoogle Scholar
Davidson, M. Risk of cardiovascular disease and sudden death in schizophrenia. J Clin Psychiatry 2002;63 (Suppl. 9):511.Google Scholar
Jeste, DV, Gladsjo, JA, Lindamer, LA, Lacro, JP. Medical comorbidity in schizophrenia. Schizophr Bull 1996;22: 413430.CrossRefGoogle Scholar
Stanton, JM. Weight gain associated with neuroleptic medication: a review. Schizophrenia Bull 1995;21: 463472. CrossRefGoogle ScholarPubMed
Davis, JM, Chen, N. Clinical profile of an atypical antipsychotic: risperidone. Schizophrenia Bull 2002;28: 4361. CrossRefGoogle ScholarPubMed
Coodin, S. Body mass index in persons with schizophrenia. Can J Psychiatry 2001;46: 549555.CrossRefGoogle ScholarPubMed
Theisen, FM, Linden, A, Geller, Fet al. Prevalence of obesity in adolescent and young adult patients with and without schizophrenia and in relation to antipsychotic medication. J Psychiatr Res 2001;35: 339345.CrossRefGoogle Scholar
Aquila, R. Management of weight gain in patients with schizophrenia. J Clin Psychiatry 2002;63(Suppl. 4):3336.Google ScholarPubMed
National Heart, Lung, and Blood Institute. First Federal Obesity Clinical Guidelines. NIH News Release, June 17 1998. Bethesda, MD: NHLBI, 1998. Google Scholar
Stedman, T, Welman, J. The distribution of adipose tissue in female in-patients receiving psychotropic drugs. Br J Psychiatry 1993;162: 249250.CrossRefGoogle ScholarPubMed
Sharpe, JK, Hills, AP. Anthrometry and adiposity in a group of people with chronic mental illness. Aus NZ J Psychiatry 1998;32: 7781. CrossRefGoogle Scholar
Lapidus, L, Bengtsson, C, Larsson, Bet al. Distribution of adipose tissue and risk of cardiovascular disease and death: a 12 year follow up of participants in the population study of Gothenburg, Sweden. Br Med J 1984;289: 12571261. CrossRefGoogle ScholarPubMed
Ananth, J, Burgoyne, K, Gadasally, R. Comparison of weight gain associated with three atypical antipsychotic drugs and haloperidol. Int J Neuropsychopharmacol 2000;3(Suppl. 1):S163. Google Scholar
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: 765774.CrossRefGoogle ScholarPubMed
Beasley, CM. Safety of olanzapine. J Clin Psychiatry Monogr 1997;15: 1921. Google Scholar
Barak, Y. No weight gain among elderly schizophrenia patients after 1 year of risperidone treatment. J Clin Psychiatry 2002;63: 117119.CrossRefGoogle ScholarPubMed
Gomez, JC, Sacristan, JA, Hernandez, Jet al. The safety of olanzapine compared with other antipsychotic drugs: results of an observational prospective study in patients with schizophrenia (EFESO Study). Pharmacoepidemiologic Study of Olanzapine in Schizophrenia. J Clin Psychiatry 2000;61: 335343.CrossRefGoogle Scholar
Ganguli, R, Brar, JS, Ayrton, Z. Weight gain over 4 months in schizophrenia patients. a comparison of olanzapine and risperidone. Schizophrenia Res 2001; 49: 261267. CrossRefGoogle ScholarPubMed
Taylor, DM, McAskill, R. Atypical antipsychotics and weight gain – a systematic review. Acta Psychiatr Scand 2000;101: 416432.CrossRefGoogle ScholarPubMed
Patil, KB. Comparative Weight Change with Atypical Antipsychotic Treatment. Presented at the American Psychiatric Association 2001 Annual Meeting, 5–10 May 2001, New Orleans, LA. Washington, DC: American Psychiatric Association, 2001. Google Scholar
Simpson, MM, Goetz, RR, Devlin, MJet al. Weight gain and antipsychotic medication: differences between antipsychotic-free and treatment periods. J Clin Psychiatry 2001;62: 694700.CrossRefGoogle ScholarPubMed
Henderson, DC, Cagliero, E, Gray, Cet al. Clozapine, diabetes mellitus, weight gain,and lipid abnormalities: a five-year naturalistic study. Am J Psychiatry 2000;157: 975981.CrossRefGoogle ScholarPubMed
Henderson, DC. Atypical antipsychotic-induced diabetes mellitus: how strong is the evidence? CNS Drugs 2002;16: 7789. Google Scholar
Kinon, BJ, Milton, DR, Gilmore, JA. Continued improvement in quality of life despite weight change during olanzapine treatment. Int J Neuropsychopharmacol 2000;3(Suppl. 1):S154. Google Scholar
Wirshing, DA, Wirshing, WC, Kysar, Let al. Novel antipsychotics: comparison of weight gain liabilities. J Clin Psychiatry 1999;60: 358363.CrossRefGoogle ScholarPubMed
Casey, DE, Zorn, Sh. The pharmacology of weight gain with antipsychotics. J Clin Psychiatry 2001;62(Suppl. 7):410.Google ScholarPubMed
Seeman, P, Kapur, S. Schizophrenia: more dopamine, more D2 receptors. Proc Natl Acad Sci USA 2000;97: 73637365. CrossRefGoogle ScholarPubMed
Eliosoff, RV. The obese patient: are drugs an option? Can J Diagnosis 1997;14: 7994. Google Scholar
Fujisawa, T, Ikegami, H, Yamato, Eet al. Association of Trp64Arg mutation of the β3-adrenergic-receptor with NIDDM and body weight gain. Diabetologia 1996;39: 349352.CrossRefGoogle ScholarPubMed
Schotte, A, Janssen, PF M, Gommeren, Wet al. Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology 1996;124: 5773.CrossRefGoogle ScholarPubMed
Mantzoros, CS. The role of leptin in human obesity and disease: a review of current evidence. Ann Intern Med 1999;130: 671680.CrossRefGoogle ScholarPubMed
Kraus, T, Haack, M, Schuld, Aet al. Body weight and leptin plasma levels during treatment with antipsychotic drugs. Am J Psychiatry 1999;156: 312314.Google ScholarPubMed
Atmaca, M, Kuloglu, M, Tezcan, Eet al. Weight gain, serum leptin and triglyceride levels in patients with schizophrenia on antipsychotic treatment with quetiapine, olanzapine and haloperidol[letter]. Schizophrenia Res 2003;60: 99100. CrossRefGoogle ScholarPubMed
Herrán, A, García-Unzueta, MT, Amado, JTet al. Effects of long-term treatment with antipsychotics on serum leptin levels. Br J Psychiatry 2001;179: 5962.CrossRefGoogle ScholarPubMed
Reaven, GM. Role of insulin resistance in human disease. Diabetes 1986;37: 15951607. CrossRefGoogle ScholarPubMed
Newcomer, JW, Haupt, DW, Fucetola, Ret al. Abnormalities in glucose regulation during antipsychotic treatment of schizophrenia. Arch General Psychiatry 2002;59: 337345. CrossRefGoogle ScholarPubMed
Cohn, TA, Remington, G, Lieter, L, Kameh, H. Antipsychotic Medication and Insulin Resistance. Abstract NR555. Presented at the American Psychiatric Association 2001 Annual Meeting, 5–10 May 2001, New Orleans, LA. Washington, DC: American Psychiatric Association, 2001. Google ScholarPubMed
Baptista, T. Atypical antipsychotic drugs and glucose dysregulation[letter]. Can J Psychiatry 2002;47: 9496.Google ScholarPubMed
Lean, M. Clinical Handbook of Weight Management. London: Martin Dunitz, 1998. Google Scholar
Calle, EE, Rodriguez, C, Walker-Thurmond, K, Thun, MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of US adults. N Engl J Med 2003;348: 16251638.CrossRefGoogle Scholar
Brown, S, Inskip, H, Barraclough, B. Causes of the excess mortality of schizophrenia. Br J Psychiatry 2000;177: 212217.CrossRefGoogle ScholarPubMed
Ryan, MCM, Thakore, JH. Physical consequences of schizophrenia and its treatment. The metabolic syndrome. Life Sci 2002;71: 239257.CrossRefGoogle ScholarPubMed
Brown, S, Birtwistle, J, Roe, Let al. The unhealthy lifestyle of people with schizophrenia. Psychol Med 1999;29: 697701.CrossRefGoogle ScholarPubMed
Henderson, DC, Ettinger, ER. Schizophrenia and diabetes. Int Rev Neurobiol 2002;51: 481501.CrossRefGoogle ScholarPubMed
McIntyre, RS, McCann, SM, Kennedy, SH. Antipsychotic metabolic effects: weight gain, diabetes mellitus, and lipid abnormalities. Can J Psychiatry 2001;46: 273281.CrossRefGoogle ScholarPubMed
Gianfrancesco, F, Grogg, AL, Mahmoud, RAet al. Differential effects of risperidone, olanzapine, cloza- pine and conventional antipsychotics on type 2 diabetes: findings from a large health plan database. J Clin Psychiatry 2002;63: 920930. Google Scholar
Caro, J, Ward, A, Levinton, Cet al. The risk of diabetes during olanzapine use compared with risperidone use: a retrospective database analysis.J Clin Psychiatry 2002;63: 11351139. Google ScholarPubMed
Liebzeit, KA, Markowitz, JS, Caley, CF. New onset diabetes and atypical antipsychotics. Europ Neuropsychopharmacol 2001;11: 2532. CrossRefGoogle ScholarPubMed
Iqbal, N, Oldan, RL, Baird, Get al. Diabetes Mellitus Induced by Atypical Antipsychotics. Presented at the 59th American Psychiatric Association Institute on Psychiatric Services, October 25–29, 2000, Philadelphia. Google Scholar
Mir, S, Taylor, D. Atypical antipsychotics and hyperglycaemia. Int Clin Psychopharmacol 2001;16: 6374.CrossRefGoogle ScholarPubMed
Ananth, J, Venkatesh, R, Burgoyne, Ket al. Atypical antipsychotic drug use and diabetes. Psychother Psychosom 2002;71: 244254.CrossRefGoogle ScholarPubMed
Hedenmalm, K, Hägg, S, Ståhl, Met al. Glucose intolerance with atypical antipsychotics. Drug Safety 2002;25: 11071116.CrossRefGoogle ScholarPubMed
Henderson, DC. Atypical antipsychotic-induced diabetes mellitus. How strong is the evidence? CNS Drugs 2002; 16: 7789.CrossRefGoogle ScholarPubMed
Koro, CE, Fedder, DO, L'Italien, GJet al. Assessment of independent effect of olanzapine and risperidone on risk of diabetes among patients with schizophrenia: population based nested case-control study. Br Med J 2002;325: 243245. CrossRefGoogle ScholarPubMed
Lindenmayer, J-P, Nathan, A-M, Smith, RC. Hyperglycaemia associated with the use of atypical antipsychotics. J Clin Psychiatry 2001;62(Suppl. 23):3038. Google Scholar
Jin, H, Meyer, JM, Veste, 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;14: 5964.CrossRefGoogle ScholarPubMed
Lindenmayer, J-P, Czobor, P, Volavka, Jet al. Changes in glucose and cholesterol levels in patients with schizophrenia treated with typical or atypical antipsychotics. Am J Psychiatry 2003;160: 290296.CrossRefGoogle ScholarPubMed
Kato, MM, Goodnick, PJ. Antipsychotic medication: effects on regulation of glucose and lipids. Expert Opin Pharmacother 2001;2: 15711582.CrossRefGoogle ScholarPubMed
Wilson, DR, D'Souza, L, Sarkar, Net al. New-onset diabetes and ketoacidosis with atypical antipsychotics. Schizophrenia Res 2002;59: 16. CrossRefGoogle ScholarPubMed
Domon, SE, Cargile, CS. Quetiapine-associated hyperglycaemia and hypertriglyceridemia[letter]. J Am Acad Child Adolesc Psychiatry 2002;41: 495496.CrossRefGoogle ScholarPubMed
Bouchard, RH, Demers, M-F, Simoneau, Iet al. Atypical antipsychotics and cardiovascular risk in schizophrenic patients[letter]. J Clin Psychopharmacol 2001;21: 110111.CrossRefGoogle ScholarPubMed
Procyshyn, RM, Kennedy, NB, Marriage, Set al. Plasma protein and lipoprotein distribution of clozapine. Am J Psychiatry 2001;158: 949951.CrossRefGoogle ScholarPubMed
Meyer, JM. Effects of atypical antipsychotics on weight and serum lipid levels. J Clin Psychiatry 2001;62 (Suppl. 27):2734.Google ScholarPubMed
Koro, CE, Fedder, DO, L'Italien, GJet al. An assessment of the independent effects of olanzapine and risperidone exposure on the risk of hyperlipidemia in schizophrenic patients. Arch Gen Psychiatry 2002;59: 10211026.CrossRefGoogle ScholarPubMed
Meyer, JM. A retrospective comparison of weight, lipid, and glucose changes between risperidone- and olanzapine-treated inpatients: metabolic outcomes after 1 year. J Clin Psychiatry 2002;63: 425433.CrossRefGoogle ScholarPubMed
Chue, P, Welch, R. Investigation of the Metabolic Effects of Antipsychotics in Patients with Schizophrenia. Presented at the 51st Annual Meeting of the Canadian Psychiatric Association, November 15–19, 2001, Montreal, Canada. CrossRefGoogle Scholar
Martin, A, L'Ecuyer, S. Triglyceride, cholesterol and weight changes among risperidone-treated youths. A retrospective study. Europ Child Adolesc Psychiatry 2002;11: 129133. CrossRefGoogle ScholarPubMed
Kawachi, I. Physical and psychological consequences of weight gain. J Clin Psychiatry 1999;60(Suppl. 21):59.Google ScholarPubMed
Kurtzhaler, I, Fleischhacker, WW. The clinical implications of weight gain in schizophrenia. J Clin Psychiatry 2001;62(Suppl. 7):3237. Google Scholar
Allison, DB, Mackell, JA, McDonnell, DD. The impact of weight gain on quality of life among persons with schizophrenia. Psychiatr Serv 2003;54: 565567.CrossRefGoogle ScholarPubMed
Perkins, DO. Adherence to antipsychotic medication. J Clin Psychiatry 1999;60(Suppl. 21):2530.Google Scholar
Perkins, DO. Predictors of non-compliance inpatients with schizophrenia. J Clin Psychiatry 2002;63: 11211128.CrossRefGoogle Scholar
Fleischhacker, WW, Meise, U, Günther, Vet al. Compliance with antipsychotic drug treatment: influence of side effects. Acta Psychiatr Scand 1994;89(Suppl. 382):1115. Google Scholar
National Schizophrenia Fellowship. A Question of Choice. Available at http://www.rethink.org/research/pdfs/choice.pdf. London: NSF, 2000. Google Scholar
Buis, W. Patients' opinions concerning side effects of depot neuroleptics. Am J Psychiatry 1992;149: 844845.Google ScholarPubMed
Fakhouri, W. Extent of distress caused by adverse experiences associated with antipsychotic treatment. J Eur Coll Neuropsychopharmacol 1999;9: S285. CrossRefGoogle Scholar
Weiden, PJ, Mackell, J, McDonnell, DD. Obesity as a risk factor for antipsychotic noncompliance. J Eur Coll Neuropsychopharmacol 2000;10(Suppl. 3):S289. CrossRefGoogle Scholar
Sachs, GS, Guille, C. Weight gain associated with use of psychotic medications. J Clin Psychiatry 1999;60: 1619.Google Scholar
Allison, DB, Mackell, J. Healthcare resource use and body mass index among individuals with schizophrenia. Int J Neuropsychopharmacol 2000;3(Suppl. 1):S124. Google Scholar
Weiden, PJ, Mackell, JA, McDonnell, DD. Recent weight gain and the cost of acute service use among individuals with schizophrenia. J Eur Coll Neuropsychopharmacol 2001;11: S271. CrossRefGoogle Scholar
Fontaine, KR, Barofsky, I, Andersen, REet al. Impact of weight loss on health-related quality of life. Qual Life Res 1999;8: 275277.CrossRefGoogle ScholarPubMed
Greenberg, I, Chan, S, Blackburn, GL. Nonpharmacologic and pharmacologic management of weight gain. J Clin Psychiatry 1999;60(Suppl. 21):3136.Google ScholarPubMed
Blackburn, GL. Weight gain and antipsychotic medication. J Clin Psychiatry 2000;61(Suppl. 8):3641.Google ScholarPubMed
Ball, MP, Coons, VB, Buchanan, RW. A program for treating olanzapine-related weight gain. Psychiatr Serv 2001;52: 967969.CrossRefGoogle ScholarPubMed
Littrell, Kh, Petty, RG, Hilligoss, NMet al. Educational Interventions for the Management of Antipsychotic-Related Weight Gain. Abstract NR244. Presented at the American Psychiatric Association Annual Meeting, 5–10 May, 2001, New Orleans, LA. Washington, DC: American Psychiatric Association, 2001. Google Scholar
Cohn, T, Miles, J, Blake, Jet al. A Novel Weight Management Program for Young Adults at Risk for Antipsychotic-induced Weight Gain. Presented at the XXIInd CINP Congress, July 9–23 2000, Brussels, Belgium.Google Scholar
Floris, M, Lejeune, J, Deberdt, W. Effect of amantadine on weight gain during olanzapine treatment. Europ Neuropsychopharmacol 2001;11: 181182. CrossRefGoogle ScholarPubMed
Cavazzoni, P, Tanaka, Y, Roychowdhury, SM, Breier, A, Allison, DB, Nizatidine for prevention of weight gain with olazapine: a double-blind placebo-controlled trial. Eur Neuropsychopharmacol 2003;13: 8185. Google Scholar