Antipsychotic effects on estimated 10-year coronary heart disease risk in the CATIE schizophrenia study

Johns Hopkins Medical Institutions, Welch Center for Prevention, Epidemiology and Clinical Research, 2024 East Monument Street, Suite 2-500, Baltimore, MD 21287, United States.
Schizophrenia Research (Impact Factor: 3.92). 10/2008; 105(1-3):175-87. DOI: 10.1016/j.schres.2008.07.006
Source: PubMed

ABSTRACT Persons with schizophrenia die earlier than the general population, in large part due to cardiovascular disease. The study objective was to examine effects of different antipsychotic treatments on estimates of 10-year coronary heart disease (CHD) risk calculated by the Framingham Heart Study formula.
Change in 10-year risk for CHD was compared between treatment groups in 1125 patients followed for 18 months or until treatment discontinuation in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Schizophrenia Trial.
The covariate-adjusted mean change in 10-year CHD risk differed significantly between treatments. Olanzapine was associated with a 0.5% (SE 0.3) increase and quetiapine, a 0.3% (SE 0.3) increase; whereas risk decreased in patients treated with perphenazine, -0.5% (SE 0.3), risperidone, -0.6% (SE 0.3), and ziprasidone -0.6% (SE 0.4). The difference in 10-year CHD risk between olanzapine and risperidone was statistically significant (p=0.004). Differences in estimated 10-year CHD risk between drugs were most marked in the tertile of subjects with a baseline CHD risk of at least 10%. Among individual CHD risk factors used in the Framingham formula, only total and HDL cholesterol levels differed between treatments.
These results indicate that the impact on 10-year CHD risk differs significantly between antipsychotic agents, with olanzapine producing the largest elevation in CHD risk of the agents studied in CATIE.

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Available from: Jeffrey A Lieberman, Sep 28, 2015
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    • "The prevalence of metabolic syndrome in people with SMI is reported to be 37–61.6% globally (Brunero et al. 2009; John et al. 2009; McEnvoy et al. 2005; van Winkel et al. 2008), and rates of cardiovascular disease and diabetes are more than double that of the general population (Daumit et al. 2008; De Hert et al. 2009; Goff et al. 2005; Morgan et al. 2011). The literature reviewed for the present study (Barnett et al. 2007; Edward et al. 2010; Lambert 2009; 2011; Lambert & Chapman 2004; Rege 2008; Usher et al. 2006) strongly endorses the implementation of a targeted cardiometabolic monitoring (CMM) system, based on metabolic syndrome criteria, as the first step towards addressing the poor cardiometabolic health outcomes for consumers of mental health services. "
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    ABSTRACT: People with serious mental illness are reported to live up to 25 years less than the general population. Cardiovascular disease and diabetes risk factors, as well as mental health, treat-ment, lifestyle, service provision, and socioeconomic factors, all contribute to this health inequity. Cardiometabolic monitoring (CMM) is one strategy used to attend to some cardiometabolic risk factors. The present study aimed to explore factors that influence decisions to undertake CMM in an Australian adult community mental health service. A CMM audit tool was designed to capture demographic, clinical, and care-provision factors. A 6-month retrospective file audit from the total population of consumers of an adult community mental health service was undertaken, where no existing CMM guidelines or practices were in place. The study findings confirmed a higher prevalence of cardiometabolic disorders in the study population compared to the general population. Complete CMM occurred in 24% of the study population (n = 94). No consumer demographic, socioeconomic, or clinical characteristics, or care-provision factors, were found to be predictors of complete CMM. The random manner in which CMM was observed to occur in the study highlights the need for standardized CMM guidelines and capacity-building strategies to improve current CMM practices.
    International journal of mental health nursing 07/2014; 23(6). DOI:10.1111/inm.12085 · 1.95 Impact Factor
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    • "Several atypical antipsychotic drugs, in particular olanzapine and clozapine, are associated with metabolic adverse effects such as obesity, dyslipidemia, and derangements in glucose metabolism, which contribute to the increased risk for cardiovascular disorders observed in patients suffering from schizophrenia (American Diabetes Association, 2004; Daumit et al., 2008; McGrath et al., 2008). Rodents are commonly used to model antipsychotic-induced metabolic adverse effects, with hyperphagia and weight gain consistently replicated after subchronic olanzapine administration to female rats, either orally or via injections (Albaugh et al., 2006; Baptista et al., 1993; Choi et al., 2007; Goudie et al., 2002; Minet- Ringuet et al., 2006; Skrede et al., 2012a). "
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    ABSTRACT: Rats are used as animal models in the study of antipsychotic-induced metabolic adverse effects, with oral drug administration yielding hyperphagia, weight gain and, in some cases, lipogenic effects. However, the rapid half-life of these drugs in rats, in combination with development of drug tolerance after a few weeks of treatment, has limited the validity of the model. In order to prevent fluctuating drug serum concentrations seen with daily repeated administrations, we injected female rats with a single intramuscular dose of long-acting olanzapine formulation. The olanzapine depot injection yielded plasma olanzapine concentrations in the range of those achieved in patients, and induced changes in metabolic parameters similar to those previously observed with oral administration, including increased food intake, weight gain and elevated plasma triglycerides. Moreover, the sensitivity to olanzapine was maintained beyond the 2-3 wk of weight gain observed with oral administration. In a separate olanzapine depot experiment, we aimed to clarify the role of hypothalamic AMP-activated protein kinase (AMPK) in olanzapine-induced weight gain, which has been subject to debate. Adenovirus-mediated inhibition of AMPK was performed in the arcuate (ARC) or the ventromedial hypothalamic (VMH) nuclei in female rats, with subsequent injection of olanzapine depot solution. Inhibition of AMPK in the ARC, but not in the VMH, attenuated the weight-inducing effect of olanzapine, suggesting an important role for ARC-specific AMPK activation in mediating the orexigenic potential of olanzapine. Taken together, olanzapine depot formulation provides an improved mode of drug administration, preventing fluctuating plasma concentrations, reducing handling stress and opening up possibilities to perform complex mechanistic studies.
    The International Journal of Neuropsychopharmacology 01/2014; 17(1):91-104. DOI:10.1017/S1461145713000862 · 4.01 Impact Factor
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    • "Individuals with serious mental illnesses are at greatly increased risk of a number of medical comorbidities including obesity [1], metabolic syndrome [2-4], diabetes mellitus [4-6], and subsequent early mortality [7-9], primarily from cardiovascular disease [2,10,11]. The causes of these elevated cardiometabolic risks can include factors such as poor access to medical care [12,13], poor nutrition [14], sedentary lifestyle [11], and smoking [11,15] but they can also be exacerbated by the antipsychotic agents prescribed to treat mental health conditions [16-23]. Because many individuals diagnosed with serious mental illnesses rely on antipsychotic medications as a primary component of their treatment, complementary treatments that reduce weight gain and potentially reduce associated cardiometabolic risks have been suggested by clinicians and researchers [1]. "
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    BMC Psychiatry 09/2013; 13(1):238. DOI:10.1186/1471-244X-13-238 · 2.21 Impact Factor
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