Pharmacopsychiatry 2009; 42(1): 29-34
DOI: 10.1055/s-0028-1100425
Original Paper

© Georg Thieme Verlag KG Stuttgart · New York

Effects of Six Second Generation Antipsychotics on Body Weight and Metabolism – Risk Assessment and Results from a Prospective Study

A. Tschoner 1 , J. Engl 1 , M. Rettenbacher 2 , M. Edlinger 2 , S. Kaser 1 , T. Tatarczyk 1 , M. Effenberger 1 , J. R. Patsch 1 , W. W. Fleischhacker 2 , C. F. Ebenbichler 1
  • 1Department of Internal Medicine I, Medical University Innsbruck, Innsbruck, Austria
  • 2Department of Biological Psychiatry, Medical University Innsbruck, Austria
Further Information

Publication History

received 11.06.2008 revised 25.08.2008

accepted 03.09.2008

Publication Date:
19 January 2009 (online)

Abstract

Background: Due to the association of second generation antipsychotics (SGAs) with weight gain and alterations of glucose and lipid homeostasis, we aimed to group six commonly prescribed SGAs into classes of differing risks.

Methods: Twenty-eight patients meeting the criteria for a diagnosis of schizophrenic disorder according to ICD-10 were assigned to monotherapy with olanzapine, clozapine, quetiapine, amisulpride, ziprasidone or risperidone. The levels of glucose and lipid metabolism were assessed before and after 28 days of treatment.

Results: Based on cluster analysis, olanzapine and clozapine were found to constitute a high-risk group for metabolic dysregulation while amisulpride, quetiapine, risperidone and ziprasidone could be assigned to a non-high-risk group. Subjects from the high-risk group displayed significant weight gain with concomitant increases of HOMA-IR, levels of insulin, total cholesterol, TG, LDL-C and leptin. No significant changes were observed in the non-high-risk group.

Conclusion: The results of this study support the conclusion of the Consensus Development Conference on Antipsychotic Drugs and Obesity and Diabetes that certain SGAs are associated with a higher risk for weight gain, insulin resistance and dyslipidemia.

References

  • 1 Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation.  Diabet Med. 1998;  15 539-553
  • 2 Allison DB, Casey DE. Antipsychotic-induced weight gain: a review of the literature.  J Clin Psychiatry. 2001;  62 22-31
  • 3 Allison DB, Mackell JA, MacDonnell DD. The impact of weight gain on quality of life among persons with schizophrenia.  Psychiatr Serv. 2003;  54 565-567
  • 4 American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, North American Association for the Study of Obesity . Consensus development conference on antipsychotic drugs and obesity and diabetes.  Diabetes Care. 2004;  27 596-601
  • 5 Ananth J, Venkatesh R, Burgoyne K. et al . Atypical antipsychotic induced weight gain: pathophysiology and management.  Ann Clin Psychiatry. 2004;  16 75-85
  • 6 Aquila R, Emanuel M. Weight gain and antipsychotic medications.  J Clin Psychiatry. 1999;  60 336-337
  • 7 Baptista T. Body weight gain induced by antipsychotic drugs: mechanisms and management.  Acta Psychiatr Scand. 1999;  100 3-16
  • 8 Baptista T, Beaulieu S. Are leptin and cytokines involved in body weight gain during treatment with antipsychotic drugs?.  Can J Psychiatry. 2002;  47 742-749
  • 9 Baptista T, Davila A, El Fakih Y. et al . Similar frequency of abnormal correlation between serum leptin levels and BMI before and after olanzapine treatment in schizophrenia.  Int Clin Psychopharmacol. 2007;  22 205-211
  • 10 Baptista T, Kin NM, Beaulieu S. et al . Obesity and related metabolic abnormalities during antipsychotic drug administration: mechanisms, management and research perspectives.  Pharmacopsychiatry. 2002;  35 205-219
  • 11 Beaufrere B, Morio B. Fat and protein redistribution with aging: metabolic considerations.  Eur J Clin Nutr. 2000;  54 ((Suppl. 3)) S48-S53
  • 12 Bromel T, Blum WF, Ziegler A. et al . Serum leptin levels increase rapidly after initiation of clozapine therapy.  Mol Psychiatry. 1998;  3 76-80
  • 13 Brown RR, Estoup MW. Comparison of the metabolic effects observed in patients treated with ziprasidone versus olanzapine.  Int Clin Psychopharmacol. 2005;  20 105-112
  • 14 Casey DE. Dyslipidemia and atypical antipsychotic drugs.  J Clin Psychiatry. 2004;  65 ((Suppl. 18)) 27-35
  • 15 Despres JP, Lemieux I. Abdominal obesity and metabolic syndrome.  Nature. 2006;  444 881-887
  • 16 Ebenbichler CF, Laimer M, Eder U. et al . Olanzapine induces insulin resistance: results from a prospective study.  J Clin Psychiatry. 2003;  64 1436-1439
  • 17 Ebenbichler C, Laimer M, Kranebitter M. et al . The soluble leptin receptor in olanzapine-induced weight gain: results from a prospective study.  Schizophr Res. 2005;  75 143-146
  • 18 Eder U, Mangweth B, Ebenbichler C. et al . Association of olanzapine-induced weight gain with an increase in body fat.  Am J Psychiatry. 2001;  158 1719-1722
  • 19 Engl J, Hanusch-Enserer U, Prager R. et al . The metabolic syndrome: effects of a pronounced weight loss induced by bariatric surgery.  Wien Klin Wochenschr. 2005;  117 243-254
  • 20 Engl J, Laimer M, Niederwanger A. et al . Olanzapine impairs glycogen synthesis and insulin signaling in L6 skeletal muscle cells.  Mol Psychiatry. 2005;  10 1089-1096
  • 21 Eriksson J, Franssila-Kallunki A, Ekstrand A. et al . Early metabolic defects in persons at increased risk for non-insulin-dependent diabetes mellitus.  N Engl J Med. 1989;  321 337-343
  • 22 Facchini FS, Hollenbeck CB, Jeppesen J. et al . Insulin resistance and cigarette smoking.  Lancet. 1992;  339 1128-1130
  • 23 Haslam DW, James WPT. Obesity.  Lancet. 2005;  366 1197-1209
  • 24 Haupt DW, Luber A, Maeda J. et al . Plasma leptin and adiposity during antipsychotic treatment of schizophrenia.  Neuropsychopharmacology. 2005;  30 184-191
  • 25 Henderson DC, Cagliero E, Copeland PM. et al . Glucose metabolism in patients with schizophrenia treated with atypical antipsychotic agents: a frequently sampled intravenous glucose tolerance test and minimal model analysis.  Arch Gen Psychiatry. 2005;  62 19-28
  • 26 Hofer A, Kemmler G, Eder U. et al . Quality of life in schizophrenia: the impact of psychopathology, attitude toward medication, and side effects.  J Clin Psychiatry. 2004;  65 932-939
  • 27 Hofer A, Rettenbacher MA, Edlinger M. et al . Outcomes in schizophrenia outpatients treated with amisulpride or olanzapine.  Pharmacopsychiatry. 2007;  40 1-8
  • 28 Hummer M, Kemmler G, Kurz M. et al . Weight gain induced by clozapine.  Eur Neuropsychopharmacol. 1995;  5 437-440
  • 29 Kashyap S, Belfort R, Gastaldelli A. et al . A sustained increase in plasma free fatty acids impairs insulin secretion in nondiabetic subjects genetically predisposed to develop type 2 diabetes.  Diabetes. 2003;  52 2461-2474
  • 30 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;  59 1021-1026
  • 31 Kraus T, Haack M, Schuld A. et al . Body weight and leptin plasma levels during treatment with antipsychotic drugs.  Am J Psychiatry. 1999;  156 312-314
  • 32 Laimer M, Ebenbichler CF, Kranebitter M. et al . Olanzapine-induced hyperglycemia: role of humoral insulin resistance-inducing factors.  J Clin Psychopharmacol. 2005;  25 183-185
  • 33 Larsson H, Elmstahl S, Ahren B. Plasma leptin levels correlate to islet function independently of body fat in postmenopausal women.  Diabetes. 1996;  45 1580-1584
  • 34 Lieberman JA, Stroup TS, MacEvoy JP. et al . Effectiveness of antipsychotic drugs in patients with chronic schizophrenia.  N Engl J Med. 2005;  353 1209-1223
  • 35 Manson JE, Willett WC, Stampfer MJ. et al . Body weight and mortality among women.  N Engl J Med. 1995;  333 677-685
  • 36 Matthews DR, Hosker JP, Rudenski AS. et al . Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.  Diabetologia. 1985;  28 412-419
  • 37 Melkersson K. Clozapine and olanzapine, but not conventional antipsychotics, increase insulin release in vitro.  Eur Neuropsychopharmacol. 2004;  14 115-119
  • 38 Melkersson K, Dahl ML. Adverse metabolic effects associated with atypical antipsychotics: literature review and clinical implications.  Drugs. 2004;  64 701-723
  • 39 Melkersson KI, Dahl ML. Relationship between levels of insulin or triglycerides and serum concentrations of the atypical antipsychotics clozapine and olanzapine in patients on treatment with therapeutic doses.  Psychopharmacology (Berl). 2003;  170 157-166
  • 40 Melkersson KI, Hulting AL. Insulin and leptin levels in patients with schizophrenia or related psychoses – a comparison between different antipsychotic agents.  Psychopharmacology (Berl). 2001;  154 205-212
  • 41 Melkersson KI, Hulting AL, Brismar KE. Elevated levels of insulin, leptin, and blood lipids in olanzapine-treated patients with schizophrenia or related psychoses.  J Clin Psychiatry. 2000;  61 742-749
  • 42 Melkersson K, Khan A, Hilding A. et al . Different effects of antipsychotic drugs on insulin release in vitro.  Eur Neuropsychopharmacol. 2001;  11 327-332
  • 43 Meyer JM. Novel antipsychotics and severe hyperlipidemia.  J Clin Psychopharmacol. 2001;  21 369-374
  • 44 Newcomer JW. Metabolic considerations in the use of antipsychotic medications: a review of recent evidence.  J Clin Psychiatry. 2007;  68 ((Suppl. 1)) 20-27
  • 45 Newcomer JW. Second-generation (atypical) antipsychotics and metabolic effects: a comprehensive literature review.  CNS Drugs. 2005;  19 ((Suppl. 1)) 1-93
  • 46 Rader DJ. Effect of insulin resistance, dyslipidemia, and intra-abdominal adiposity on the development of cardiovascular disease and diabetes mellitus.  Am J Med. 2007;  120 S12-18
  • 47 Rettenbacher MA, Ebenbichler C, Hofer A. et al . Early changes of plasma lipids during treatment with atypical antipsychotics.  Int Clin Psychopharmacol. 2006;  21 369-372
  • 48 Sinha MK, Opentanova I, Ohannesian JP. et al . Evidence of free and bound leptin in human circulation. Studies in lean and obese subjects and during short-term fasting.  J Clin Invest. 1996;  98 1277-1282
  • 49 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;  87 2918-2923
  • 50 Stevens J, Cai J, Pamuk ER. et al . The effect of age on the association between body-mass index and mortality.  N Engl J Med. 1998;  338 1-7
  • 51 Tandon R, Fleischhacker WW. Comparative efficacy of antipsychotics in the treatment of schizophrenia: a critical assessment.  Schizophr Res. 2005;  79 145-155
  • 52 Gaal LF Van. Long-term health considerations in schizophrenia: metabolic effects and the role of abdominal adiposity.  Eur Neuropsychopharmacol. 2006;  16 ((Suppl. 3)) S142-S148
  • 53 Gaal LF Van, Mertens IL, Block CE De. Mechanisms linking obesity with cardiovascular disease.  Nature. 2006;  444 875-880
  • 54 Wetterling T. Bodyweight gain with atypical antipsychotics. A comparative review.  Drug Saf. 2001;  24 59-73
  • 55 Wirshing DA, Wirshing WC, Kysar L. et al . Novel antipsychotics: comparison of weight gain liabilities.  J Clin Psychiatry. 1999;  60 358-363
  • 56 Wu RR, Zhao JP, Liu ZN. et al . Effects of typical and atypical antipsychotics on glucose-insulin homeostasis and lipid metabolism in first-episode schizophrenia.  Psychopharmacology (Berl). 2006;  186 572-578
  • 57 Zhang Y, Proenca R, Maffei M. et al . Positional cloning of the mouse obese gene and its human homologue.  Nature. 1994;  372 425-432
  • 58 Zimmet PZ. Kelly West Lecture 1991. Challenges in diabetes epidemiology – from West to the rest.  Diabetes Care. 1992;  15 232-252

Correspondence

C. F. EbenbichlerMD 

Department of Internal Medicine I

Medical University Innsbruck

Anichstraße 35

6020 Innsbruck

Austria

Phone: +43/512/504/285 37

Fax: +43/512/504/285 39

Email: Christoph.Ebenbichler@i-med.ac.at

    >