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Metabolic Findings From the CATIE Trial and Their Relation to Tolerability

Published online by Cambridge University Press:  07 November 2014

Henry A. Nasrallah*
Affiliation:
Dr. Nasrallah is professor of psychiatry, neurology, and neuroscience and associate dean at the, University of Cincinnati College of Medicine in Ohio
*
Henry A. Nasrallah, MD, 231 Albert Sabin Way, ML 0559m Cincinnati, OH 45267-0559; Tel: 513-558-4615; Fax:, 513-558-4616; E-mail:, [email protected]

Abstract

The overall effectiveness of antipsychotics for the management of schizophrenia is restricted by their side-effect profiles, particularly over an extended treatment period. Intolerable side effects can reduce patient adherence to medication and often lead to treatment discontinuation. Some side effects that result from antipsychotic use are precursors to the metabolic syndrome, which is prevalent among individuals with schizophrenia and represents a significant source of cardiovascular risk. The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia study assessed the efficacy of the atypical antipsychotics olanzapine, quetiapine, risperidone, and ziprasidone relative to the conventional drug perphenazine. Additional assessments included the metabolic effects of these agents in patients with schizophrenia and the incidence of negative side effects. No significant differences were found between treatment groups for time to discontinuation due to intolerability, but the rates of side effects significantly differed (P=.04). For metabolic parameters, olanzapine was associated with greater and significant adverse effects on weight, lipids, and glucose metabolism versus the other antipsychotics tested. The CATIE results show that important distinctions exist among currently available atypical antipsychotics. Physicians should be aware of the propensity of these drugs to increase the risks of cardiovascular disease and diabetes in treated patients and tailor individual treatment decisions accordingly. This article highlights the metabolic findings from the CATIE schizophrenia study, and explores the differences shown by atypical antipsychotics, with regard to metabolic side effects that increase cardiovascular risk.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2006

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References

1.Grundy, SM, Brewer, B, Cleeman, JI, Smith, SC Jr, Lenfant, C and for the Conference Participants. Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation. 2004;109(3):433438.CrossRefGoogle ScholarPubMed
2.Reaven, GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988;37(12):15951607.CrossRefGoogle ScholarPubMed
3.Meyer, JM, Koro, CE. The effects of antipsychotic therapy on serum lipids: a comprehensive review. Schizophr Res. 2004;70:117.CrossRefGoogle Scholar
4.National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106(25);31433421.CrossRefGoogle Scholar
5. World Health Organization. Definition, diagnosis and classification of diabetes mellitus and its complications: report of a WHO Consultation. Part 1: diagnosis and classification of diabetes mellitus. Geneva, Switzerland: World Health Organization; 1999. Available at: http://whqlibdoc.who.int/hq/1999/WHO_NCD_NCS_99.2.pdf. Accessed February 12, 2006.Google Scholar
6.Einhorn, D, Reaven, GM, Cobin, RH, et al.American College of Endocrinology position statement on the insulin resistance syndrome. Endocr Pract. 2003;9(3):237252.CrossRefGoogle Scholar
7.Alberti, KG, Zimmet, P, Shaw, J; IDF Epidemiology Task Force Consensus Group. The metabolic syndrome--a new worldwide definition. Lancet. 2005;366(9491):10591062.CrossRefGoogle Scholar
8.Kahn, R, Buse, J, Ferrannini, E, Stern, M; American Diabetes Association; European Association for the Study of Diabetes. The metabolic syndrome: time for a critical appraisal: joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2005;28(9):22892304.CrossRefGoogle Scholar
9.Grundy, SM, Cleeman, JI, Daniels, SR, et al.American Heart Association; National Heart, Lung, and Blood Institute. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005;112(17):2735–52.CrossRefGoogle ScholarPubMed
10.Wannamethee, SG, Shaper, AG, Lennon, L, Morris, RW. Metabolic syndrome versus Framingham Risk Score for prediction of coronary heart disease, stroke, and type 2 diabetes mellitus. Arch Intern Med. 2005;165:26442650.CrossRefGoogle Scholar
11.Ford, ES. Prevalence of the metabolic syndrome defined by the International Diabetes Federation among adults in the US. Diabetes Care. 2005;28:27452749.CrossRefGoogle Scholar
12.Park, Y-W, Zhu, S, Palaniappan, L, Heshka, S, Carnethon, MR, Heymsfield, SB. The metabolic syndrome: prevalence and associated risk factor findings in the US population from the Third National Health and Nutrition Examination Survey, 1988-1994. Arch Intern Med. 2003;163(4):427436.CrossRefGoogle ScholarPubMed
13.Newcomer, JW. Second-generation (atypical) antipsychotics and metabolic effects a comprehensive literature review. CNS Drugs. 2005;19(suppl 1):193.CrossRefGoogle ScholarPubMed
14.Casey, DE, Haupt, DW, Newcomer, JW, et al.Antipsychotic-induced weight gain and metabolic abnormalities: Implications for increased mortality in patients with schizophrenia. J Clin Psychiatry. 2004;65(S7):418.Google ScholarPubMed
15.Cohn, T, Prud'homme, D, Streiner, D, Kameh, H, Remington, G. Characterizing coronary heart disease risk in chronic schizophrenia: high prevalence of the metabolic syndrome. Can J Psychiatry. 2004;49(11): 753760.CrossRefGoogle ScholarPubMed
16.Meyer, JM, Nasrallah, HA, McEvoy, JP, et al.The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial: clinical comparison of subgroups with and without the metabolic syndrome. Schizophr Res. 2005;80(1):918.CrossRefGoogle ScholarPubMed
17.Henderson, DC, Ettinger, EP. Glucose Intolerance and Diabetes in Schizophrenia. In: Meyer, JM, Nasrallah, H, eds. Medical Illness and Schizophrenia. Washington, DC: American Psychiatric Press, Inc.; 2003:99114.Google Scholar
18.Meyer, JM. Cardiovascular Illness and Hyperlipidemia in Patients with Schizophrenia. In: Meyer, JM, Nasrallah, H, eds. Medical Illness and Schizophrenia. Washington, DC: American Psychiatric Press, Inc.; 2003:5380.Google Scholar
19.Allison, DB, Casey, DE. Antipsychotic-induced weight gain: a review of the literature. J Clin Psychiatry. 2001;62:2231.Google ScholarPubMed
20.Jin, H, Meyer, JM, Jeste, DV. Atypical antipsychotics and glucose dysregulation: a systematic review. Schizophrenia Res. 2004;71:195212.CrossRefGoogle ScholarPubMed
21.Nasrallah, HA, Newcomer, JW. Atypical antipsychotics and metabolic dysregulation: evaluating the risk/benefit ratio equation and improving the standard of care. J Clin Psychopharmacol. 2004;24(5 suppl 1):S714.CrossRefGoogle Scholar
22.Weiden, PJ, Mackell, JAMcDonnell, D. Obesity as a risk factor for antipsychotic noncompliance. Schizophr Res. 2004;66(1):5157.CrossRefGoogle ScholarPubMed
23.Simpson, GM. Atypical antipsychotics and the burden of disease. Am J Manag Care. 2005;11(8):S235S241.Google ScholarPubMed
24.Nasrallah, H. A review of the effect of atypical antipsychotics on weight. Psycho-neuroendocrinology. 2003;28(suppl 1):8396.CrossRefGoogle ScholarPubMed
25.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. J Clin Psychiatry. 2004;65(2):267272.CrossRefGoogle Scholar
26.Travis, MJ, Burns, T, Dursun, S, et al.Aripiprazole in schizophrenia: consensus guidelines. Int J Clin Pract. 2005;59:485495.CrossRefGoogle ScholarPubMed
27.Perry, PJ, Argo, TR, Carnahan, RM, et al.The association of weight gain and olanzapine plasma concentrations. J Clin Psychopharmacol. 2005;25:250254CrossRefGoogle ScholarPubMed
28.Haberfellner, EM, Rittmannsberger, H. Weight gain during long-term treatment with olanzapine: a case series. Int Clin Psychopharmacol. 2004;19:251253.CrossRefGoogle ScholarPubMed
29.Allison, DB, Mentore, JL, Heo, M, et al.Antipsychotic-induced weight gain: A comprehensive research synthesis. Am J Psychiatry. 1999;156(11):1686–96.CrossRefGoogle ScholarPubMed
30.Lieberman, JA, Stroup, TS, McEvoy, JP, et, al, for the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med. 2005;353(12):12091223.CrossRefGoogle ScholarPubMed
31.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;80(1):4553.CrossRefGoogle ScholarPubMed
32.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;80(1):1932.CrossRefGoogle ScholarPubMed
33.Mukherjee, S, Decina, P, Bocola, V, Saraceni, F, Scapicchio, PL. Diabetes mellitus in schizophrenic patients. Compr Psychiatry. 1996;37(1):6873.CrossRefGoogle ScholarPubMed
34.Nasrallah, HA, McEvoy, JP, Meyer, JM, et al.Low rates of treatment for metabolic disorders in the CATIE schizophrenia trial. Neuropsychopharmacol. 2005;(suppl 1):204.Google Scholar