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The Role of Atypical Antipsychotics in Glucose/Insulin Dysregulation and the Evolving Role of the Psychiatrist in a New Era of Drug Treatment Options

Published online by Cambridge University Press:  07 November 2014

Abstract

This article examines the issue of atypical antipsychotics, glucose/insulin, and other metabolic derangements (ie, metabolic syndrome), including a general introduction to the health, concerns of our patients, a review of the literature, possible mechanisms of antipsychotic induced glucose dysregulation, monitoring approaches, and management and prevention of metabolic syndrome. Literature review leads to mechanism hypotheses and risk estimations, leading to guidelines for monitoring and treatment. The patient population suffers from a higher degree of baseline metabolic dysregulation resulting in cardiovascular disease through components of the metabolic syndrome, and this risk increases with administration of atypical antipsychotic medication at different rates, depending on both drug and patient risk factors. The growing knowledge of mechanisms behind drug induced glucose/insulin and other metabolic dysregulation, as well as advances in pharmacogenomics, will help refine drug selection and monitoring for adverse, life-threatening metabolic effects.

Type
Review Article
Copyright
Copyright © Cambridge University Press 2004

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References

REFERENCES

1. Lebovitz, HE. Insulin resistance: definition and consequences. Exp Clin Endocrinol Diabetes. 2001;109(suppl 2):S135–S148.CrossRefGoogle ScholarPubMed
2. Lebovitz, HE. Diagnosis, classification, and pathogenesis of diabetes mellitus. J Clin Psychiatry. 2001;62(suppl 11):59.Google Scholar
3. Osby, U, Correia, N, Brandt, L, Ekbom, A, Sparen, P. Mortality and causes of death in schizophrenia in Stockholm County, Sweden. Sctapphr Res. 2000;45:2128.Google Scholar
4. Melkersson, KI, Hulting, A, Brismar, KE. Elevated levels of insulin, leptin, and blood lipids in olanzapine-treated patients with schizophrenia or related psychoses. J Clin Psychiatry. 2000;61:742749.Google Scholar
5. Sernyak, MJ, Gulanski, B, Leslie, D, Rosenheck, R. Undiagnosed hyperglycemia in clozapine-treated patients with schizophrenia. J Clin Psychiatry. 2003;64:605608.CrossRefGoogle ScholarPubMed
6. Sernyak, MJ, Leslie, DL, Alarcon, RD, Losonczy, MF, Rosenheck, R. Association of diabetes mellitus with use of atypical neuroleptics in the treatment of schizophrenia. Am J Psychiatry. 2002;159:561566.CrossRefGoogle ScholarPubMed
7. Dixon, L, Weiden, P, Delahanty, J, et al. Prevalence and correlates of diabetes in national schizophrenia samples. Schizophr Bull. 2000;26:903912.Google Scholar
8. Horrobin, DF, Bennett, CN. New gene targets related to schizophrenia and other psychiatric disorders: enzymes, binding proteins and transport proteins involved in phospholipid and fatty acid metabolism. Prostaglandins Leuhot Essent Fatty Acids. 1999;60:217234.Google Scholar
9. Lund, BC, Perry, PJ, Brooks, JM, Arndt, S. Clozapine use in patients with schizophrenia and the risk of diabetes, hyperlipidemia, and hypertension: a claimsbased approach. Arch Gen Psychiatry. 2001;58:11721176.Google Scholar
10. Hagg, S, Joelsson, L, Mjorndal, T, Spigset, O, Oja, G, Dahlqvist, R. Prevalence of diabetes and impaired glucose tolerance in patients treated with clozapine compared with patients treated with conventional depot neuroleptic medications. J Clin Psychiatry. 1998;59:294299.CrossRefGoogle ScholarPubMed
11. Henderson, DC, Cagliero, E, Gray, C, et al. Clozapine, diabetes mellitus, weight gain, and lipid abnormalities: a five-year naturalistic study. Am J Psychiatry. 2000;157:975981.Google Scholar
12. Melkersson, KI, Hulting, A, Brismar, KE. Different influences of classical antipsychotics and ctozapine on glucose-insulin homeostasis in patients with schizophrenia or related psychoses. J Clin Psychiatry. 1999;60:783791.CrossRefGoogle ScholarPubMed
13. Newcomer, JW, Haupt, DW, Fucetola, R, et al. Abnormalities in glucose regulation during antipsychotic treatment of schizophrenia. Arch Gen Psychiatry. 2002;59:337345.CrossRefGoogle ScholarPubMed
14. American Diabetes Association. Clinical Practice Recommendations 2003. Journal of Clinical and Applied Research and Education. 2003;26(suppl 1):S1–S156.Google Scholar
15. Koller, E, Schneider, B, Bennett, K, Dubitsky, G. Clozapine-associated diabetes. Am J Med. 2001;111:716723.Google Scholar
16. Koller, E, Doraiswamy, PM. Olanzapine-associated diabetes mellitus. Pharmacotherapy. 2002;22:841852.Google Scholar
17. Gianfrancesco, FD, Grogg, AL, Mahmoud, RA, Wang, RH, Nasrallah, HA. Differential effects of risperidone, olanzapine, clozapine, and conventional antipsychotics on type 2 diabetes: findings from a large health plan database. J Clin Psychiatry. 2002;63:920930.Google Scholar
18. Kinon, BJ, Basson, BR, Gilmore, JA, Tollefson, GD. Long-term olanzapine treatment: weight change and weight-related health factors in schizophrenia. J Clin Psychiatry. 2001;62:92100.Google Scholar
19. Olefsky, JM. Insulin resistance. In: Diaietes Mellitus. 5th ed. Stamford, Conn: Appleton and Lange; 1997:513552.Google Scholar
20. Garg, A. Insulin resistance in the pathogenesis of dyslipidemia. Diabetes Care. 1996;19:387389.CrossRefGoogle ScholarPubMed
21. Lindenmayer, JP, Czobor, P, Volavka, J, et 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
22. Caro, JJ, Ward, A, Levinton, C, Robinson, K. The risk of diabetes during olanzapine use compared with risperidone use: a retrospective databse analysis. J Clin Psychiatry. 2002;63:11351139.Google Scholar
23. Kenny, SJ, Aubert, RE, Geiss, LS. Prevlance and incidence of non-insulin-dependent diabetes. In: Harris, M, Cowie, C, Stern, M, Boyko, E, Reiber, G, Bennett, P, eds. Diabetes in America. 2nd ed. Bethesda, MD: National Institutes Health; 1995:4767. Publication No. 95–1468.Google Scholar
24. Koro, CE, Fedder, DO, L'ltalien, GJ, et al. Assessment of independent effect of olanzapine and risperidone on risk of diabetes among patients with schizophrenia: population based nested case-control study. BMJ. 2002;325:243.CrossRefGoogle ScholarPubMed
25. Dwyer, DS, Liu, Y, Bradley, RJ. Dopamine receptor antagonists modulate glucose uptake in rat pheochromocytoma (PC12) cells. Neurosci Lett. 1999;274:151154.Google Scholar
26. Brismar, K, Grill, V, Efendic, S, Hall, K. The insulin-like growth factor binding protein-1 in low and high insulin responders before and during dexamethasone treatment. Metabcolism. 1991;40:728732.CrossRefGoogle ScholarPubMed
27. Hilding, A, Brismar, K, Degerblad, M, Thoren, M, Hall, K. Altered relation between circulating levels of insulin-like growth factor binding protein-1 and insulin in growth hormone deficient patients and insulin dependent diabetic patients compared to that in healthy subjects. J Clin Endocrinol Metab. 1995;80:26462652.Google ScholarPubMed
28. Uvnas-Moberg, K, Ahlenius, S, Alster, P, Hillegaart, V. Effects of selective serotonin and dopamine agonists on plasma levels of glucose, insulin and glucagon in the rat. Neuroendocrinology. 1996;63:269274.CrossRefGoogle ScholarPubMed
29. Wozniak, KM, Linnoila, M. Hyperglycemic properties of serotonin receptor antagonists. Life Sci. 1991:49:101109.Google Scholar
30. Tecott, LH, Sun, LM, Akana, SF, et al. Eating disorder and epilepsy in mice lacking 5-HT2C serotonin receptors. Nature. 1995;374:542546.Google Scholar
31. Kolaczynski, JW, Nyce, MR, Considine, RV, et al. Acute and chronic effect of insulin on leptin production in humans: studies in vivo and in vitro. Diabetes. 1996;45:699701.Google Scholar
32. Tanizawa, Y, Okuya, S, Ishihara, H, Asano, T, Yada, T, Oka, Y. Direct stimulation of basal insulin secretion by physiological concentrations of leptin in pancreatic beta cells. Endocrinology. 1997:138:45134516.Google Scholar
33. Seufert, J, Kieffer, TJ, Leech, CA, et al. Leptin suppression of insulin secretion and gene expression in human pancreatic islets: implications for the development of adipogenic diabetes mellitus. J Clin Endocrinol Metab. 1999;84:670676.Google ScholarPubMed
34. Dwyer, DS, Pinkofsky, HB, Liu, Y, Bradley, RJ. Antipsychotic drugs affect glucose uptake and the expression of glucose transporters in PCI 2 cells. Prog NeuroPsychopharmacol Biol Psychiatry. 1999;23:6980.Google Scholar
35. Gould, RJ, Murphy, KM, Reynolds, IJ, Snyder, SH. Antischizophrenic drugs of the diphenylbutylpiperidine type act as calcium channel antagonists. Proc Nad Acad Sci USA. 1983;80:51225125.Google Scholar
36. Galizzi, JP, Fosset, M, Romey, G, Laduron, P, Lazdunski, M. Neuroleptics of the diphenylbutylpiperidine series are potent calcium channel inhibitors. Proc Natl Acad Sci USA. 1986:83:75137517.CrossRefGoogle ScholarPubMed
37. Newcomer, JW. Metabolic disturbances associated with antipsychotic use. J Clin Psychiatry. 2001;62(suppl 27):34; discussion 40–41.Google ScholarPubMed
38. Meltzer, HY. Putting metabolic side effects into perspective: risks versus benefits of atypical antipsychotics. J Clin Psychiatry. 2001;62(suppl 27):3539; discussion 40–41.Google ScholarPubMed
39. Zoler, M. Antipsychotics linked to weight gain, diabetes. Clinical Psychiatry News. 1999;27:20.Google Scholar
40. American Diabetes Association. Screening for Type 2 Diabetes. Diabetes Care. 2003;26(suppl 1):S21–S24.Google Scholar
41. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of The 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). JAMA. 2001:285:24862497.Google Scholar
42. Wemeke, U, Taylor, D, Sanders, TA. Options for the pharmacological management of obesity in patients treated with atypical antipsychotics. Curr Psychiatry. 2002;8:145160.Google Scholar
43. Avandia [package insert]. Research Triangle Park, NC: GlaxoSmithKline; May 2002.Google Scholar
44. Allison, DB, Fontaine, KR, Heo, M, et al. The distribution of body mass index among individuals with and without schizophrenia. J Clin Psychiatry. 1999;60:215220.Google Scholar
45. Actos [package insert]. Lincolnshire, IL: Takeda Pharmaceuticals America, Inc. and Indianapolis, Ind: Eli Lilly and Co.; July 2002.Google Scholar
46. Gouda, HE, Khan, A, Schwartz, J, Cohen, RI. Liver failure in a patient treated with long-term rosiglitazone therapy. Am J Med. 2001;111:584585.CrossRefGoogle Scholar
47. Forman, LM, Simmons, DA, Diamond, RH. Hepatic failure in a patient taking rosiglitazone. Ann Intern Med. 2000;132:118121.Google Scholar
48. Vieweg, W, Adler, R, Fernandez, A. Weight control and antipsychotics: how to tip the scales away from diabetes and heart disease. Curr Psychiatry. 2002;1:1019.Google Scholar
49. Meltzer, HY. Suicidality in schizophrenia: a review of the evidence for risk factors and treatment options. Curr Psychiatry Rep. 2002;4:279283.CrossRefGoogle ScholarPubMed
50. Vangala, VR, Brown, ES, Suppes, T. Clozapine associated with decreased suicidality in bipolar disorder: a case report. Bipolar Disard. 1999;2:123124.CrossRefGoogle Scholar
51. Frankenburg, FR, Zanarini, MC. Uses of clozapine in nonschizophrenic patients. Harv Rev Psychiatry. 1994;2:142150.CrossRefGoogle ScholarPubMed
52. Benedetti, F, Sforzini, L, Colombo, C, Maffei, C, Smeraldi, E. Low-dose clozapine in acute and continuation treatment of severe borderline personality disorder. J Clin Psychiatry. 1998;59:103107.CrossRefGoogle ScholarPubMed
53. Ciapparelli, A, Dell'Osso, L, Pini, S, Chiavacci, MC, Fenzi, M, Cassano, GB. Clozapine for treatment-refractory schizophrenia, schizoaffective disorder, and psychotic bipolar disorder: a 24-month naturalistic study. J Clin Psychiatry. 2000;61:329334.Google Scholar
54. Fontaine, KR, Heo, M, Harrigan, EP, et al. Estimating the consequences of antipsychotic induced weight gain on health and mortality rate. Psychiatry Res. 2001;101:277288.CrossRefGoogle ScholarPubMed
55. Basile, VS, Masellis, M, Mclntyre, RS, Melrzer, HY, Lieherman, JA, Kennedy, JL. Genetic dissection of atypical antipsychotic-induced weight gain: novel preliminary data on the pharmacogenetic puzzle. J Clin Psychiatry. 2001;62(suppl 23):4564.Google Scholar
56. Rusnak, JM, Kisabeth, RM, Herbert, DP, McNeil, DM. Pharmacogenomics: a clinician's primer on emerging technologies for improved patient care. Mayo Clin Proc. 2001;76:299309.Google Scholar
57. Basile, VS, Masellis, M, Ozdemir, V, et al. Application of pharmacogenetics to schizophrenia: emerging insights from studies of clozapine and tardive dyskinesia. In: Breier, A, Brier, A, Bymaster, F, Tran, P, Lewis, M, eds. Current Issues in the Psychopharmacology of Schizophrenia. New York, NY: Lippincott Williams & Wilkens; 2001:85110.Google Scholar
58. Masellis, M, Basile, VS, Ozdemir, V, Meltzer, HY, Macciardi, FM, Kennedy, JL. Pharmacogenetics of antipsychotic treatment: lessons learned from clozapine. Biol Psychiatry. 2000;47:252266.Google Scholar
59. Arranz, MJ, Munro, J, Osborne, S, Collier, D, Kerwin, RW. Applications of pharmacogenetics in psychiatry: personalisation of treatment. Expert Opin Pharmacother. 2001;2:537542.Google Scholar
60. Reynolds, GP, Zhang, ZJ, Zhang, XB. Association of antipsychotic drug-induced weight gain with a 5-HT2C-receptor gene polymorphism. Lancet. 2002;359:20862087.CrossRefGoogle ScholarPubMed
61. Yuan, X, Yamada, K, Ishiyama-Shigemoto, S, Koyama, W, Nonaka, K. Identification of polymorphic loci in the promoter region of the serotonin 5-HT2C receptor gene and their association with obesity and type II diabetes. Diabetologia. 2000;43:373376.Google Scholar