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Published in: Drug Safety 15/2002

01-12-2002 | Original Research Article

Glucose Intolerance with Atypical Antipsychotics

Authors: Dr Karin Hedenmalm, Staffan Hägg, Malin Ståhl, Örjan Mortimer, Olav Spigset

Published in: Drug Safety | Issue 15/2002

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Abstract

Background: Previous studies have suggested that the atypical antipsychotics clozapine and olanzapine may be associated with an increased risk of glucose intolerance and diabetes mellitus. Early studies have also suggested an association between use of conventional antipsychotics and the development of glucose intolerance.
Objective: To examine quantitatively the association between glucose intolerance including diabetes mellitus and the use of the atypical antipsychotics clozapine, olanzapine or risperidone, and to identify possible risk factors for the development of glucose intolerance during treatment with these drugs.
Methods: All reports suggestive of glucose intolerance for clozapine, olanzapine and risperidone were identified in the WHO database for adverse drug reactions. In the analyses of possible risk factors for glucose intolerance all other reports of adverse drug reactions for clozapine, olanzapine and risperidone were used as reference. Using the Bayesian Confidence Propagation Neural Network method, the strengths of the associations over time between glucose intolerance and the use of these drugs were analysed. For comparison, the strengths of the associations between glucose intolerance and the use of the conventional antipsychotics haloperidol and chlorpromazine were also analysed.
Results: Clozapine, olanzapine and risperidone were significantly associated with glucose intolerance. In contrast, chlorpromazine and haloperidol were not associated with glucose intolerance. For clozapine, olanzapine and risperidone grouped together, the following potential risk factors for glucose intolerance were identified: an underlying diabetic condition (odds ratio [OR] 10.22, 95% CI 8.20–12.73), an increase in weight (OR 2.36, 95% CI 1.76–3.17), male gender (OR 1.27, 95% CI 1.11–1.47), and concomitant use of valproic acid (OR 1.97, 95% CI 1.61–2.40), selective serotonin reuptake inhibitors (OR 1.63, 95% CI 1.33–1.99) or buspirone (OR 2.24, 95% CI 1.33–3.77).
Conclusion: Treatment with clozapine, olanzapine or risperidone appears to be associated with an increased risk of glucose intolerance.
Literature
1.
go back to reference Waddington JL, O’Callaghan E. What makes an antipsychotic agent ‘atypical’? conserving the definition. CNS Drugs 1997; 7: 341–6CrossRef Waddington JL, O’Callaghan E. What makes an antipsychotic agent ‘atypical’? conserving the definition. CNS Drugs 1997; 7: 341–6CrossRef
2.
3.
go back to reference Popli AP, Konicki PE, Jurjus GJ, et al. Clozapine and associated diabetes mellitus. J Clin Psychiatry 1997; 58: 108–11PubMedCrossRef Popli AP, Konicki PE, Jurjus GJ, et al. Clozapine and associated diabetes mellitus. J Clin Psychiatry 1997; 58: 108–11PubMedCrossRef
4.
go back to reference Wirshing DA, Spellberg BJ, Erhart SM, et al. Novel antipsychotics and new onset diabetes. Biol Psychiatry 1998; 44: 778–83PubMedCrossRef Wirshing DA, Spellberg BJ, Erhart SM, et al. Novel antipsychotics and new onset diabetes. Biol Psychiatry 1998; 44: 778–83PubMedCrossRef
5.
go back to reference Hägg S, Joelsson L, Mjörndal T, et al. 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: 294–9PubMedCrossRef Hägg S, Joelsson L, Mjörndal T, et al. 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: 294–9PubMedCrossRef
6.
go back to reference Melkersson KI, Hulting A-L, Brismar KE. Different influences of classical antipsychotics and clozapine on glucose-insulin homeostasis in patients with schizophrenia or related psychoses. J Clin Psychiatry 1999; 60: 783–91PubMedCrossRef Melkersson KI, Hulting A-L, Brismar KE. Different influences of classical antipsychotics and clozapine on glucose-insulin homeostasis in patients with schizophrenia or related psychoses. J Clin Psychiatry 1999; 60: 783–91PubMedCrossRef
7.
go back to reference Goldstein LE, Sporn J, Brown S, et al. New-onset diabetes mellitus and diabetic ketoacidosis associated with olanzapine treatment. Psychosomatics 1999; 40: 438–43PubMedCrossRef Goldstein LE, Sporn J, Brown S, et al. New-onset diabetes mellitus and diabetic ketoacidosis associated with olanzapine treatment. Psychosomatics 1999; 40: 438–43PubMedCrossRef
8.
go back to reference Bettinger TL, Mendelson SC, Dorson PG, et al. Olanzapine-induced glucose dysregulation. Ann Pharmacother 2000; 34: 865–7PubMedCrossRef Bettinger TL, Mendelson SC, Dorson PG, et al. Olanzapine-induced glucose dysregulation. Ann Pharmacother 2000; 34: 865–7PubMedCrossRef
9.
go back to reference Arnesson GA. Phenothiazine derivates and glucose metabolism. J Neuropsychiat 1964; 5: 181–98 Arnesson GA. Phenothiazine derivates and glucose metabolism. J Neuropsychiat 1964; 5: 181–98
10.
go back to reference Thonnard-Neumann E. Phenothiazines and diabetes in hospitalised women. Am J Psychiatry 1968; 124: 978–82PubMed Thonnard-Neumann E. Phenothiazines and diabetes in hospitalised women. Am J Psychiatry 1968; 124: 978–82PubMed
11.
go back to reference Proakis AG, Mennear JH, Miya TS, et al. Phenothiazines-induced hyperglycemia: relation to CNS and adrenal effects. Proc Soc Exp Biol Med 1971; 137: 1385–8PubMed Proakis AG, Mennear JH, Miya TS, et al. Phenothiazines-induced hyperglycemia: relation to CNS and adrenal effects. Proc Soc Exp Biol Med 1971; 137: 1385–8PubMed
12.
go back to reference Schwarz L, Munoz R. Blood sugar levels in patients treated with chlorpromazine. Am J Psychiatry 1968; 125: 253–5PubMed Schwarz L, Munoz R. Blood sugar levels in patients treated with chlorpromazine. Am J Psychiatry 1968; 125: 253–5PubMed
13.
go back to reference Ward JL. Glucose tolerance in schizophrenia. Orthomol Psychiatry 1972; 44: 137–40 Ward JL. Glucose tolerance in schizophrenia. Orthomol Psychiatry 1972; 44: 137–40
14.
go back to reference Dynes JB. Diabetes in schizophrenia and diabetes in nonpsychotic medical patients. Dis Nerv Syst 1969; 30: 341–4PubMed Dynes JB. Diabetes in schizophrenia and diabetes in nonpsychotic medical patients. Dis Nerv Syst 1969; 30: 341–4PubMed
15.
go back to reference McKee HA, D’Arcy PF, Wilson P. Diabetes and schizophrenia: a preliminary study. J Clin Hosp Pharm 1986; 11: 297–9PubMed McKee HA, D’Arcy PF, Wilson P. Diabetes and schizophrenia: a preliminary study. J Clin Hosp Pharm 1986; 11: 297–9PubMed
16.
go back to reference Brambilla F, Guastalla A, Guerrini A, et al. Glucose-insulin metabolism in chronic schizophrenia. Dis Nerv Syst 1976; 37: 98–103PubMed Brambilla F, Guastalla A, Guerrini A, et al. Glucose-insulin metabolism in chronic schizophrenia. Dis Nerv Syst 1976; 37: 98–103PubMed
17.
go back to reference Mukherjee S, Decina P, Bocola V, et al. Diabetes mellitus in schizophrenic patients. Compr Psychiatry 1996; 37: 68–73PubMedCrossRef Mukherjee S, Decina P, Bocola V, et al. Diabetes mellitus in schizophrenic patients. Compr Psychiatry 1996; 37: 68–73PubMedCrossRef
18.
go back to reference Stanton JM. Weight gain associated with neuroleptic medication: a review. Schizophr Bull 1995; 21: 463–72PubMedCrossRef Stanton JM. Weight gain associated with neuroleptic medication: a review. Schizophr Bull 1995; 21: 463–72PubMedCrossRef
19.
go back to reference Wirshing DA, Wirshing WC, Kysar L, et al. Novel antipsychotics: comparison of weight gain liabilities. J Clin Psychiatry 1999; 60: 358–63PubMedCrossRef Wirshing DA, Wirshing WC, Kysar L, et al. Novel antipsychotics: comparison of weight gain liabilities. J Clin Psychiatry 1999; 60: 358–63PubMedCrossRef
20.
go back to reference 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: 975–81PubMedCrossRef 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: 975–81PubMedCrossRef
21.
go back to reference Ghaeli P, Dufresne RL. Serum triglyceride levels in patients treated with clozapine. Am J Health Syst Pharm 1996; 53: 2079–81PubMed Ghaeli P, Dufresne RL. Serum triglyceride levels in patients treated with clozapine. Am J Health Syst Pharm 1996; 53: 2079–81PubMed
22.
go back to reference Spivak B, Lamschtein C, Talmon Y, et al. The impact of clozapine treatment on serum lipids in chronic schizophrenic patients. Clin Neuropharmacol 1999; 22: 98–101PubMedCrossRef Spivak B, Lamschtein C, Talmon Y, et al. The impact of clozapine treatment on serum lipids in chronic schizophrenic patients. Clin Neuropharmacol 1999; 22: 98–101PubMedCrossRef
23.
go back to reference Gaulin BD, Markowitz JS, Caley CF, et al. Clozapine-associated elevation in serum triglycerides. Am J Psychiatry 1999; 156: 1270–2PubMed Gaulin BD, Markowitz JS, Caley CF, et al. Clozapine-associated elevation in serum triglycerides. Am J Psychiatry 1999; 156: 1270–2PubMed
24.
go back to reference Brömel T, Blum WF, Ziegler A, et al. Serum leptin levels increase rapidly after initiation of clozapine therapy. Mol Psychiatry 1998; 3: 76–80PubMedCrossRef Brömel T, Blum WF, Ziegler A, et al. Serum leptin levels increase rapidly after initiation of clozapine therapy. Mol Psychiatry 1998; 3: 76–80PubMedCrossRef
25.
go back to reference Kraus T, Haack M, Schuld A, et al. Body weight and leptin plasma levels during treatment with antipsychotic drugs. Am J Psychiatry 1999; 156: 312–4PubMed Kraus T, Haack M, Schuld A, et al. Body weight and leptin plasma levels during treatment with antipsychotic drugs. Am J Psychiatry 1999; 156: 312–4PubMed
26.
go back to reference Melamed Y, Mazeh D, Elizur A. Risperidone treatment for a patient suffering from schizophrenia and IDDM [letter]. Can J Psychiatry 1998; 43: 956PubMed Melamed Y, Mazeh D, Elizur A. Risperidone treatment for a patient suffering from schizophrenia and IDDM [letter]. Can J Psychiatry 1998; 43: 956PubMed
27.
go back to reference Bate A, Lindquist M, Edwards IR, et al. A Bayesian neural network method for adverse drug reaction signal generation. Eur J Clin Pharmacol 1998; 54: 315–21PubMedCrossRef Bate A, Lindquist M, Edwards IR, et al. A Bayesian neural network method for adverse drug reaction signal generation. Eur J Clin Pharmacol 1998; 54: 315–21PubMedCrossRef
28.
go back to reference Orre R, Lansner A, Bate A, et al. Bayesian neural networks with confidence estimations applied to data mining. Comput Stat Data Anal 2000; 34: 473–93CrossRef Orre R, Lansner A, Bate A, et al. Bayesian neural networks with confidence estimations applied to data mining. Comput Stat Data Anal 2000; 34: 473–93CrossRef
29.
go back to reference Henderson DC. Atypical antipsychotic-induced diabetes mellitus: how strong is the evidence? CNS Drugs 2002; 16: 77–89PubMedCrossRef Henderson DC. Atypical antipsychotic-induced diabetes mellitus: how strong is the evidence? CNS Drugs 2002; 16: 77–89PubMedCrossRef
30.
31.
go back to reference Mir S, Taylor D. Atypical antipsychotics and hyperglycemia. Int Clin Psychopharmacol 2001; 16: 63–73PubMedCrossRef Mir S, Taylor D. Atypical antipsychotics and hyperglycemia. Int Clin Psychopharmacol 2001; 16: 63–73PubMedCrossRef
32.
go back to reference Allison DB, Mentore JL, Heo M, et al. Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry 1999; 156: 1686–96PubMed Allison DB, Mentore JL, Heo M, et al. Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry 1999; 156: 1686–96PubMed
33.
go back to reference Isojärvi JIT, Rättyä J, Myllylä VV, et al. Valproate, lamotrigine, and insulin-mediated risks in women with epilepsy. Ann Neurol 1998; 43: 446–51PubMedCrossRef Isojärvi JIT, Rättyä J, Myllylä VV, et al. Valproate, lamotrigine, and insulin-mediated risks in women with epilepsy. Ann Neurol 1998; 43: 446–51PubMedCrossRef
34.
go back to reference Goodnick PJ, Henry JH, Buki VM. Treatment of depression in diabetes mellitus. J Clin Psychiatry 1995; 56: 128–36PubMed Goodnick PJ, Henry JH, Buki VM. Treatment of depression in diabetes mellitus. J Clin Psychiatry 1995; 56: 128–36PubMed
35.
go back to reference Petty KJ. Hyperglycemia associated with paroxetine [letter]. Ann Intern Med 1996; 125: 782PubMed Petty KJ. Hyperglycemia associated with paroxetine [letter]. Ann Intern Med 1996; 125: 782PubMed
36.
go back to reference Erenmemisoglu A, Ozdogan UK, Saraymen R, et al. Effect of some antidepressants on glycaemia and insulin levels of normoglycaemic and alloxan-induced hypeglycemic mice. J Pharm Pharmacol 1999; 51: 741–3PubMedCrossRef Erenmemisoglu A, Ozdogan UK, Saraymen R, et al. Effect of some antidepressants on glycaemia and insulin levels of normoglycaemic and alloxan-induced hypeglycemic mice. J Pharm Pharmacol 1999; 51: 741–3PubMedCrossRef
37.
go back to reference Yamada J, Sugimoto Y, Inoue K. Selective serotonin reuptake inhibitors fluoxetine and fluvoxamine induce hyperglycemia by different mechanisms. Eur J Pharmacol 1999; 382: 211–5PubMedCrossRef Yamada J, Sugimoto Y, Inoue K. Selective serotonin reuptake inhibitors fluoxetine and fluvoxamine induce hyperglycemia by different mechanisms. Eur J Pharmacol 1999; 382: 211–5PubMedCrossRef
38.
go back to reference Good MI. Lethal interaction of clozapine and buspirone? Am J Psychiatry 1997; 154: 1472–3PubMed Good MI. Lethal interaction of clozapine and buspirone? Am J Psychiatry 1997; 154: 1472–3PubMed
39.
go back to reference Uvnäs-Moberg K, Ahlenius S, Alster P, et al. Effects of selective serotonin and dopamine agonists on plasma levels of glucose, insulin and glucagon in the rat. Neuroendocrinology 1996; 63: 269–74PubMedCrossRef Uvnäs-Moberg K, Ahlenius S, Alster P, et al. Effects of selective serotonin and dopamine agonists on plasma levels of glucose, insulin and glucagon in the rat. Neuroendocrinology 1996; 63: 269–74PubMedCrossRef
Metadata
Title
Glucose Intolerance with Atypical Antipsychotics
Authors
Dr Karin Hedenmalm
Staffan Hägg
Malin Ståhl
Örjan Mortimer
Olav Spigset
Publication date
01-12-2002
Publisher
Springer International Publishing
Published in
Drug Safety / Issue 15/2002
Print ISSN: 0114-5916
Electronic ISSN: 1179-1942
DOI
https://doi.org/10.2165/00002018-200225150-00005

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