Skip to main content
Erschienen in: Drug Safety 15/2002

01.12.2002 | Original Research Article

Glucose Intolerance with Atypical Antipsychotics

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

Erschienen in: Drug Safety | Ausgabe 15/2002

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat 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.
Zurück zum Zitat Stanniland C, Taylor D. Tolerability of atypical antipsychotics. Drug Saf 2000; 22(3): 195–214PubMedCrossRef Stanniland C, Taylor D. Tolerability of atypical antipsychotics. Drug Saf 2000; 22(3): 195–214PubMedCrossRef
3.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat Edwards IR, Wiholm B-E, Martinez C. Concepts in risk-benefit assessment. Drug Saf 1996; 15: 1–7PubMedCrossRef Edwards IR, Wiholm B-E, Martinez C. Concepts in risk-benefit assessment. Drug Saf 1996; 15: 1–7PubMedCrossRef
31.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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
Metadaten
Titel
Glucose Intolerance with Atypical Antipsychotics
verfasst von
Dr Karin Hedenmalm
Staffan Hägg
Malin Ståhl
Örjan Mortimer
Olav Spigset
Publikationsdatum
01.12.2002
Verlag
Springer International Publishing
Erschienen in
Drug Safety / Ausgabe 15/2002
Print ISSN: 0114-5916
Elektronische ISSN: 1179-1942
DOI
https://doi.org/10.2165/00002018-200225150-00005

Weitere Artikel der Ausgabe 15/2002

Drug Safety 15/2002 Zur Ausgabe