Glucose intolerance with atypical antipsychotics

Drug Epidemiology Unit, Medical Products Agency, Uppsala, Sweden.
Drug Safety (Impact Factor: 2.62). 02/2002; 25(15):1107-16. DOI: 10.2165/00002018-200225150-00005
Source: PubMed

ABSTRACT 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.
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.
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.
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).
Treatment with clozapine, olanzapine or risperidone appears to be associated with an increased risk of glucose intolerance.

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Available from: Staffan Haegg, Mar 19, 2015
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    • "Among the 13 large sample retrospective studies based on prescription or safety monitoring databases, eight compared the risk of developing DM directly or indirectly between AAP and conventional antipsychotics as groups. Seven of these reports (Sernyak et al., 2002; Koro et al., 2002; Gianfrancesco et al., 2002; Kornegay et al., 2002; Hedenmalm et al., 2002; Buse et al., 2003 and Fuller et al., 2003) suggested that certain atypical agents or atypicals as a group had a significantly increased risk of new-onset DM (or increased odds ratio for the casecontrol studies) compared to conventional antipsychotics. In evaluating the risk for newonset DM among individual atypical agents, 8 of these 13 studies compared the risk among individual atypical agents or relative to conventional agents or non-users of antipsychotics. "
    Topics in the Prevention, Treatment and Complications of Type 2 Diabetes, 11/2011; , ISBN: 978-953-307-590-7
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    • "During the 1960s, there was a general acceptance that antipsychotic drugs could cause diabetes and the term "phenothiazine diabetes" was introduced. The issue was largely forgotten, until interest was rekindled with the observation that atypical antipsychotic drugs may be associated with a higher risk of IGT and diabetes as compared to conventional antipsychotics [28] [29] [30]. Most interestingly, several observations in both humans and animals support the concept that atypical antipsychotics may have profound effects on glucose metabolism, independent of psychiatric disease [5]. "
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    ABSTRACT: 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 drug-related 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.
    Diabetes & Metabolism 07/2007; 33(3):169-75. DOI:10.1016/j.diabet.2007.01.003 · 2.85 Impact Factor
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    • "Indeed, and in accordance with the observation of weight gain being a risk factor for glucose metabolism disorders in the general population, weight gain was identified in a study performed on the WHO database as a risk factor for antipsychotic-induced glucose intolerance [24]. However, only 5.6% of patients with glucose intolerance experienced weight gain. "
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    ABSTRACT: The current literature supports that schizophrenia (and bipolar disorders) appear to be associated with a higher prevalence of type 2 diabetes. Because of the silent nature of diabetes mellitus, and the fact that schizophrenic patients are not screened comprehensively for the disease, the true prevalence of hyperglycemia and diabetes may be substantially underestimated. Notably, it has been suggested that schizophrenia as such carries an increased risk, as certain characteristics of schizophrenic patients such as unhealthy life style promote the diabetes risk. This risk may be increased by antipsychotic drug treatment, as was already suggested for first-generation antipsychotics (FGA). The amount of literature on the association of SGA and metabolic disorders is much larger however, although well-controlled prospective data are sparse. Reports comprise abnormal glucose regulation, exacerbation of existing type 1 and 2 diabetes, new-onset pseudo-type 1 or type 2 diabetes, diabetic ketoacidosis, coma and death. In large-scale studies (mostly retrospective), reviews and meta-analyses, the association was not found for all drugs. NEW DATA: According to recent reviews, the risk of developing diabetes was highest for clozapine and olanzapine, followed by quetiapine and risperidone. The hierarchy of liability of weight gain, or differential effects on insulin resistance was also in the described order. Apart from disturbances in glucose metabolism, further frequent metabolic abnormalities in schizophrenic patients on SGA include features of the metabolic syndrome. Antipsychotics such as clozapine and olanzapine have also been associated with hypertriglyceridemia, while agents such as haloperidol, risperidone and ziprasidone were associated with reductions in plasma triglycerides. Amisulpride, aripiprazole and ziprasidone seem to carry the lowest risk for weight gain, diabetes and effects on insulin resistance. As a consequence, there is a shift in attention toward physical health monitoring in patients with mental health disorders. The APA and ADA as well a British working group have recently published the findings on SGA and metabolic abnormalities in a joint statement (table I).
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