Relationship Between Antipsychotic Medication Treatment and New Cases of Diabetes Among Psychiatric Inpatients

Nathan Kline Institute, Orangeburg, New York, United States
Psychiatric Services (Impact Factor: 2.41). 10/2004; 55(9):1006-13. DOI: 10.1176/
Source: PubMed

ABSTRACT This study examined data on patients with serious and persistent mental illness in a large state hospital system to determine whether patients who took second-generation antipsychotics were more likely to develop diabetes mellitus than patients who took first-generation antipsychotics.
A case-control study design was used. A new prescription of an antidiabetic medication was used to identify new cases of diabetes mellitus. Odds ratios were calculated for exposure to second-generation antipsychotics (clozapine, risperidone, olanzapine, quetiapine, and multiple second-generation antipsychotics) compared with exposure to first-generation antipsychotics. Cases and controls were identified by using a database that contained drug prescription information from the inpatient facilities that were operated by the New York State Office of Mental Health. Data from January 1, 2000, to December 31, 2002, were examined. Among 13,611 unique patients who received antipsychotics, 8,461 met entry criteria of being hospitalized for at least 60 days and not having an antidiabetic medication prescribed in the past. A total of 181 of these inpatients received prescriptions for an antidiabetic medication at least 30 days after their admission. Eight controls (N=1,448) for each case (N=181) were matched by calendar year, length of observation period, race, age group, and diagnosis, giving a total sample of 1,629 patients.
Statistically significant elevations in risk were seen among patients who received more than one second-generation antipsychotic or clozapine or quetiapine, compared with patients who received first-generation antipsychotics alone. Although not statistically significant, odds ratios for olanzapine and risperidone were also elevated. Conditional logistic regression adjusting for gender and age did not change the results.
Exposure to multiple second-generation antipsychotics or clozapine or quetiapine significantly increased the risk of treatment-emergent diabetes mellitus.

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Available from: Leslie Citrome, Sep 26, 2015
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    • "Antipsychotics are known to induce metabolic disturbances like weight gain, dyslipidemia, glycemic dysregulations or diabetes (Newcomer et al., 2002; Caro et al., 2002; Citrome et al., 2004). Over the last two decades, the risk of diabetes associated to antipsychotics attracted considerable clinical interest in psychiatry. "
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    ABSTRACT: Pharmacodynamic mechanisms of diabetes induced by antipsychotic drugs remain unclear, while numerous receptors have been suspected to be involved in the genesis of this Adverse Drug Reaction (ADR). We investigated potential relationships between antipsychotics׳ receptor occupancy (serotonin 5-HT1A, 5-HT2A, 5-HT2C, histamine H1, muscarinic M3, adrenergic α1, α2 or dopaminergic D2 D3 occupancies) and reports of diabetes using VigiBase(®), the World Health Organization (WHO) global Individual Case Safety Report (ICSR) database. All ADR reports from 15 first and second generation antipsychotic drugs recorded in VigiBase(®) were extracted. Logistic regression models, completed by disproportionality analysis, were used to determine the associations between antipsychotics׳ receptor occupancy and ICSRs of diabetes on VigiBase(®). During the study period, 94,460 ICSRs involved at least one of the 15 antipsychotics of interest. Diabetes was reported in 1799 (1.9%) patients. Clozapine was the most frequently suspected drug (n=953; 53.0%). A significant and positive association was found between histamine H1, muscarinic M3 and serotonin 5-HT2C, 5-HT2A receptor occupancies and reports of diabetes. A multivariable stepwise regression model showed that only serotonin 5-HT2c (AOR=2.13, CI 95% 1.72-2.64) and histamine H1 (AOR=1.91, CI 95% 1.38-2.64) predicted the risk for diabetes mellitus (p<0.001). Using an original pharmacoepidemiology-pharmacodynamic (PE-PD) approach, our study supports that antipsychotic drugs blocking simultaneously histamine H1 and serotonin 5-HT2C receptors are more frequently associated with diabetes reports in VigiBase(®) than other antipsychotics. These findings should encourage investigation of histamine H1 and serotonin 5-HT2C properties for predicting the risk of glycemic effects in candidate antipsychotics. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 07/2015; DOI:10.1016/j.euroneuro.2015.07.010 · 4.37 Impact Factor
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    • "Atypical antipsychotic agents are first-line therapy for symptoms of schizophrenia and other psychotic disorders. However, numerous studies have documented a higher incidence of diabetes and hyperglycemia among patients treated with atypical antipsychotics (at least partially attributed to effects of weight gain) compared to typical agents (Caro et al., 2002; Koller and Doraiswamy, 2002; Kornegay et al., 2002; Koro et al., 2002; Sernyak et al., 2002; Buse et al., 2003; Gianfrancesco et al., 2003a, 2003b; Lindenmayer et al., 2003; Citrome et al., 2004; Leslie and Rosenheck, 2004; Gianfrancesco et al., 2006; Ramaswamy et al., 2006; DuMouchel et al., 2008; Smith et al., 2008). In addition, case reports and case series have suggested that these drugs may also have acute hyperglycemic effects, occasionally leading to diabetic ketoacidosis (DKA), coma, and death (Muench and Carey, 2001; Roefaro and Mukherjee, 2001; Jin et al., 2002; Koller et al., 2003; Wilson et al., 2003; Koller et al., 2004; Takahashi et al., 2005; Marlowe et al., 2007; Kohen et al., 2008; Makhzoumi et al., 2008). "
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    ABSTRACT: Objective To evaluate the relationship between initiation of atypical antipsychotic agents and the risk of hyperglycemic emergencies. Method We conducted a multicentre retrospective cohort study using administrative health data from 7 Canadian provinces and the UK Clinical Practice Research Datalink. Hospitalizations for hyperglycemic emergencies (hyperglycemia, diabetic ketoacidosis, hyperosmolar hyperglycemic state) were compared between new users of risperidone (reference), and new users of olanzapine, other atypical antipsychotics, and typical antipsychotics. We used propensity scores with inverse probability of treatment weighting and proportional hazard models to estimate the site-specific hazard ratios of hyperglycemic emergencies in the year following drug initiation separately for adults under and over age 66 years. Site-level results were pooled using meta-analytic methods. Results Among 725,489 patients, 55% were aged 66 + years; 5% of younger and 19% of older patients had pre-existing diabetes. Hyperglycemic emergencies were rare (1–2 per 1000 person years), but more frequent in patients with pre-existing diabetes (6–12 per 1000 person years). We did not find a significant difference in risk of hyperglycemic emergencies with initiation of olanzapine versus risperidone; however heterogeneity existed between sites. The risk of an event was significantly lower with other atypical (99% quetiapine) compared to risperidone use in older patients [adjusted hazard ratio, 95% confidence interval (CI): 0.69, 0.53–0.90]. Conclusions Risk for hyperglycemic emergencies is low after initiation of antipsychotics, but patients with pre-existing diabetes may be at greater risk. The risk appeared lower with the use of quetiapine in older patients, but the clinical significance of the findings requires further study.
    Schizophrenia Research 04/2014; 154(1-3). DOI:10.1016/j.schres.2014.01.043 · 3.92 Impact Factor
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    • "The safety of polypharmacy with two AP is a matter of concern. Data from studies published so far suggest that polypharmacy may increase the risk of metabolic syndrome [21] [18] "
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    ABSTRACT: Background The term antipsychotic polypharmacy (APP) refers to the concurrent use of two or more antipsychotic drugs in schizophrenia. The aim of this study was to investigate the range of APP in schizophrenic patients discharged from psychiatric units in Poland, and to determine its demographical and clinical correlates. Methods Data on the pharmacological treatment of 207 patients with a diagnosis of schizophrenia, discharged from six psychiatric hospitals from September–December 2011 were recorded by experienced psychiatrists. Clinical and demographical information was obtained on each patient. The severity of symptoms at admission, and their improvement during hospitalization were assessed using the Clinical Global Impression Scale. Results At discharge, 52.7% of the patients were prescribed one, 42.5% two and 4.8% three antipsychotic drugs (AP). When two AP were applied, it was usually a combination of two second generation antipsychotics (SGA) (46%), or of both first generation antipsychotics (FGA) and SGA (48%). The SGA's olanzapine and risperidone were those most commonly prescribed. Patients treated with two or more AP had a higher number of previous hospitalizations than patients receiving antipsychotic monotherapy. Mood stabilizers were prescribed for nearly one third of the patients, while antidepressants and benzodiazepines were prescribed for fewer than 10%. Conclusions The prevalence of polypharmacy in Poland is similar to that reported in other countries. This may suggest that, in a substantial proportion of schizophrenic patients clinical response to the antipsychotic monotherapy is unsatisfactory. Further studies focusing on the efficacy and safety of strategies in the treatment of patients with schizophrenia not responding to antipsychotic monotherapy are necessary.
    Pharmacological reports: PR 01/2014; 66(4):613–617. · 1.93 Impact Factor
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