Olanzapine‐Associated Diabetes Mellitus

Koller, Elizabeth A.; Doraiswamy, P. Murali

doi:10.1592/phco.22.11.841.33629

Cited by 265 publications

(196 citation statements)

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“…Up to date, several studies investigating olanzapineinduced changes in glucose metabolism in patients have been published (Hedenmalm et al, 2002;Koller and Doraiswamy, 2002;Sernyak et al, 2002;Wilson et al, 2003;Simpson et al, 2004;Haupt et al, 2007). Newcomer et al (2002) tested oral glucose tolerance in chronically ill BMImatched patients with schizophrenia.…”

Section: Discussionmentioning

confidence: 99%

“…Despite the welldescribed effects of adiposity on glucose metabolism in the general population (Welch et al, 1990;Karter et al, 1996;Macor et al, 1997;Mayer-Davis et al, 1997), the underlying mechanisms for potential adiposity-independent effects of atypical antipsychotics on insulin sensitivity have not been identified yet. While most studies report an increased risk for the development of metabolic abnormalities like glucose intolerance, insulin-resistance, and consequentially DM2 in rodent (Houseknecht et al, 2005) or dog studies as well as in patients with schizophrenia (Hedenmalm et al, 2002;Koller and Doraiswamy, 2002;Newcomer et al, 2002;Sernyak et al, 2002;Wilson et al, 2003;Kane et al, 2004;Simpson et al, 2004;Henderson et al, 2005, 2006, Haupt et al, 2007, patients with schizoaffective disorder (Wilson et al, 2003;Simpson et al, 2004) or patients with mood disorder (Gianfrancesco et al, 2003) treated with atypical antipsychotics, other studies fail to confirm these correlations for healthy subjects (Sowell et al, 2002(Sowell et al, , 2003 or patients with schizophrenia (Kinon et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

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Effects of Olanzapine and Ziprasidone on Glucose Tolerance in Healthy Volunteers

Sacher

Mossaheb

Spindelegger

et al. 2007

Neuropsychopharmacol

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Atypical antipsychotics have been linked to a higher risk for glucose intolerance, and consequentially the development of type 2 diabetes mellitus (DM2). We have therefore set out to investigate the acute effects of oral administration of olanzapine and ziprasidone on whole body insulin sensitivity in healthy subjects. Using the standardized hyperinsulinemic euglycemic clamp technique we compared whole body insulin sensitivity of 29 healthy male volunteers after oral intake of either olanzapine 10 mg/day (n ¼ 14) or ziprasidone 80 mg/day (n ¼ 15) for 10 days. A significant decrease (po0.001) in whole body insulin sensitivity from 5.7 ml/h/kg ( ¼ mean, SM ¼ 0.4 ml/h/kg) at baseline to 4.7 ml/h/kg ( ¼ mean, SM ¼ 0.3 ml/h/kg) after oral intake of olanzapine (10 mg/day) for 10 days was observed. The ziprasidone (80 mg/day) group did not show any significant difference (5.2 ± 0.3 ml/h/kg baseline vs 5.1 ± 0.3 ml/h/kg) after 10 days of oral intake. Our main finding demonstrates that oral administration of olanzapine but not ziprasidone leads to a decrease in whole body insulin sensitivity in response to a hyperinsulinemic euglycemic challenge. Our finding is suggestive that not all atypical antipsychotics cause acute direct effects on glucose disposal and that accurate determination of side effect profile should be performed when choosing an atypical antipsychotic.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of Olanzapine and Ziprasidone on Glucose Tolerance in Healthy Volunteers

Sacher

Mossaheb

Spindelegger

et al. 2007

Neuropsychopharmacol

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“…Koller et al have published several analyses of anecdotal reports of diabetes occurring with clozapine [32], olanzapine [33], risperidone [34] and quetiapine [35]. All drugs were associated with either new cases of diabetes or exacerbation of pre-existing disease, and there are reports on the fatalities associated with hyperglycemia for each drug.…”

Section: Antipsychotics and Glucose Disturbancesmentioning

confidence: 99%

“…A first subgroup concerns patients with rapid onset of diabetes after antipsychotic treatment initiation. Even if infrequent, they have been reported with ketoacidotic coma, a lifethreatening condition [31][32][33][34][35]. Patients with diabetic ketoacidosis were younger, less overweight at baseline and included a higher proportion of women.…”

Section: Underlying Mechanismsmentioning

confidence: 99%

Abnormal glucose metabolism in patients treated with antipsychotics

Scheen

Hert

2007

Diabetes & Metabolism

151

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Second-generation (atypical) antipsychotic medications are of great benefit to a wide variety of people with psychiatric disorders, especially patients with schizophrenia. However, one constellation of adverse effects is an increased risk of obesity, diabetes, and metabolic syndrome. Increasing numbers of reports concerning impaired glucose tolerance, diabetes, and ketoacidosis have raised concerns about a possible association between abnormal glucose metabolism and treatment with atypical antipsychotics, although the question is still debated because of the presence of many confounding factors. A close relationship between drug-induced weight gain and risk of diabetes has been reported, emphasizing the role of insulin resistance. However, some cases of diabetes developed independently of weight gain, rather rapidly and possibly progressing to ketoacidosis, thus arguing for a severe impairment of insulin secretion. Another debated question is whether diabetes risk is a class action or a differential action. Although not fully scientifically proven yet, available evidence suggests that clozapine and olanzapine have a higher propensity to induce diabetes and metabolic syndrome compared with other atypical antipsychotic drugs, risperidone and quetiapine. Despite more limited available data, amisulpride, aripiprazole and ziprazidone showed less likelihood of precipitating diabetes. Interestingly, reversibility of drugrelated diabetes has been reported with aripiprazole. The choice of atypical antipsychotic medication for a specific patient depends on many factors, but the likelihood of developing diabetes should become an important consideration. When prescribing an atypical antipsychotic, a commitment to careful baseline screening and follow-up monitoring is essential in order to mitigate the risk of developing diabetes and associated complications.Keywords: antipsychoticsa; schizophrenia ; diabetes ; impaired glucose tolerance ; metabolic syndrome ; review RésuméLes antipsychotiques de seconde génération, appelés aussi antipsychotiques atypiques, ont apporté une aide précieuse dans la prise en charge de nombreux patients psychiatriques, en particulier ceux avec schizophrénie. Cependant, ils semblent associés à une constellation d'effets indésirables métaboliques, avec un risque accru d'obésité, de diabète et de syndrome métabolique. Un nombre croissant de publications à propos de cas de diminution de tolérance au glucose, de diabète et d'acidocétose chez des patients traités avec des antipsychotiques atypiques plaident pour une association causale possible entre une anomalie du métabolisme du glucose et le traitement par antipsychotique atypique, même si la question reste controversée suite à la présence de nombreux facteurs confondants. Une relation étroite entre la prise de poids induite par la médication et le risque accru de diabète a été rapportée, insistant sur le rôle de l'insulinorésistance. Pourtant, certains cas de diabète se développent indépendamment de toute prise pondérale, avec une évolution...

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“…The second argument is the dramatic clinical presentation of diabetes in schizophrenia. There is an enhanced risk of metabolic complications, such as ketosis, acidosis and ketoacidosis, which are associated with a mortality rate of 26.5% [4][5][6]. These features are suggestive of type 1 diabetes or latent autoimmune diabetes of adults (LADA) rather than type 2 diabetes.…”

Section: To the Editormentioning

confidence: 99%

Immunological characteristics of diabetes in schizophrenia

2005

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Abbreviations IA2: insulinoma antigen 2 . LADA: latent autoimmune diabetes of adults To the EditorIn 1899, Henry Maudsley, the first psychiatrist to link diabetes to psychiatric illness, wrote that "diabetes is a disease which often shows itself in families in which insanity prevails" [1]. With this observation, Maudsley suggested that patients with schizophrenia are genetically predisposed to diabetes. The introduction of chlorpromazine (in 1953) and, more recently, the atypical antipsychotics was followed by an increase in the number of cases of new-onset diabetes and the worsening of glycaemic control in cases of existing diabetes in patients with schizophrenia [2]. These findings suggest an iatrogenic, rather than a genetic, origin of diabetes in schizophrenia, in the form of antipsychoticinduced weight gain. However, this debate has not, as yet, been settled.In general, diabetes associated with schizophrenia is classified as type 2 diabetes. However, there are two arguments against this classification. The first argument is the rapid onset of schizophrenia-associated diabetes: over 80% of patients who develop diabetes do so within 6 months of initiating antipsychotic therapy [2]. With such a rapid onset, weight gain is unlikely to be the main stimulus for the development of the diabetes. A prospective randomised trial comparing the classical antipsychotic haloperidol with the three atypicals clozapine, olanzapine and risperidone found no relationship between glucose change and weight gain at endpoint, thereby confirming the independence of these two measures [3]. The second argument is the dramatic clinical presentation of diabetes in schizophrenia. There is an enhanced risk of metabolic complications, such as ketosis, acidosis and ketoacidosis, which are associated with a mortality rate of 26.5% [4][5][6]. These features are suggestive of type 1 diabetes or latent autoimmune diabetes of adults (LADA) rather than type 2 diabetes.Type 1 diabetes and LADA are characterised by diabetes-related antibodies, i.e. antibodies against insulin, GAD and insulinoma antigen 2 (IA2), which are found in over 80% of type 1 diabetic subjects and in fewer than 5% of the general population [7,8]. The aim of this study was to determine the prevalence of the three diabetes-related antibodies in schizophrenic patients, thereby establishing whether autoimmune phenomena play a role in diabetes associated with schizophrenia.Patients (81 men [68.1%], 38 women [31.9%]; mean age 41.5 years [SD=10.9, range 19-65]) gave informed consent to participate in the study, which was approved by the Ethics Committee of the University of Utrecht. The psychiatric diagnosis was based on the shortened version of the

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Olanzapine‐Associated Diabetes Mellitus

Abstract: Number of reports, temporal relationship to start of olanzapine therapy, relatively young age, and improvement on drug withdrawal suggest that olanzapine may precipitate or unmask diabetes in susceptible patients.

Cited by 265 publications

References 52 publications

Effects of Olanzapine and Ziprasidone on Glucose Tolerance in Healthy Volunteers

Effects of Olanzapine and Ziprasidone on Glucose Tolerance in Healthy Volunteers

Abnormal glucose metabolism in patients treated with antipsychotics

Immunological characteristics of diabetes in schizophrenia

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