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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atypical antipsychotics are the treatment of choice for patients with schizophrenia. They are generally better tolerated than conventional antipsychotics since most do not cause debilitating extrapyramidal symptoms. They are associated though with an array of cardiovascular adverse events that may affect morbid-mortality of schizophrenic patients. Orthostatic hypotension, electrocardiographic changes and metabolic syndrome (MS) are the main cardiovascular effects of atypical antipsychotics. They contribute to the overall disease burden associated with schizophrenia even though the benefit risk of such treatments still is highly favourable. We aim to review the main cardiovascular side effects of new atypical oral antipsychotics, the pharmacological mechanisms involved, and to which drugs they are particularly attributed.
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PMID:Cardiovascular risks of atypical antipsychotic drug treatment. 1756 19

There is great concern over cardiovascular disease in the schizophrenic population owing to the high incidence of cardiovascular mortality. Increased cardiovascular mortality is related to lifestyle choices (e.g., smoking and sedentary lifestyle) and a high prevalence of comorbid medical conditions, including dyslipidemia, the metabolic syndrome and Type 2 diabetes. One factor that increases cardiovascular risk is the medications used to treat the core features of schizophrenia. Adverse cardiovascular effects of antipsychotic treatment have been recognized for many decades, especially tachycardia, orthostatic hypotension and rare instances of sudden death; but, since 2000, there has been a significant shift in the focus of risk perception. The older antipsychotic literature is replete with papers primarily concerned with the physiological consequences of muscarinic cholinergic antagonism, alpha(1)-adrenergic antagonism or receptors associated with cardiac conduction, but the current literature recognizes that, for most antipsychotic-exposed patients, the more significant cardiovascular burden of treatment is mediated by metabolic adverse effects such as weight gain, dyslipidemia and diabetes mellitus. The purpose of this review is to examine the cardiovascular risks of treatment with antipsychotic medications, elucidating relevant mechanisms and differences between various agents, especially for metabolic adverse effects seen with atypical antipsychotics.
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PMID:Cardiovascular effects of antipsychotics. 1761 Mar 90

The variability of individual responses reported by the CATIE study has raised awareness of the need to reconsider personalizing prescriptions of antipsychotic medications for the purpose of establishing the best antipsychotic for each individual patient. As atypical antipsychotics are widely prescribed for severe mental illnesses other than schizophrenia and side effects are largely independent from diagnosis, personalizing antipsychotic dosing may have important public health implications. This hypothesis article emphasizes that, whereas other psychiatric medications may cause weight gain, antipsychotics appear to have additional effects. Antipsychotics may have direct effects (not explained by obesity) on hypertension, diabetes mellitus and hyperlipidemia. The clinical and pharmacoepidemiological literature appears to suggest that (1) antipsychotics rarely increase blood pressure, with the probable exception of clozapine; (2) antipsychotics (particularly clozapine and olanzapine) may interfere with glucose metabolism in a (still unknown) direct way, independently of their effects on obesity; and (3) clozapine and olanzapine (and possibly quetiapine and low-potency typical antipsychotics) may directly cause hyperlipidemia, independently of their effects on obesity. This commentary focuses on the effect sizes and the time interval/event sequence of the direct influences of antipsychotics on blood pressure, glucose metabolism and lipid metabolism. Cross-sectional lipid studies may show antipsychotic effects. It is hypothesized that it may be easier to design studies focusing on these three aspects than to design pharmacogenetic studies focusing on antipsychotic-induced weight gain or metabolic syndrome, which require long-term follow-up.
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PMID:Planning for the optimal design of studies to personalize antipsychotic prescriptions in the post-CATIE era: the clinical and pharmacoepidemiological data suggest that pursuing the pharmacogenetics of metabolic syndrome complications (hypertension, diabetes mellitus and hyperlipidemia) may be a reasonable strategy. 1761 85

The use of antipsychotics is associated with metabolic side effects, which put patients with schizophrenia or related disorders at risk for cardiovascular morbidity. The high interindividual variability in antipsychotic-induced metabolic abnormalities suggests that genetic makeup is a possible determinant. In this cross-sectional study, we investigated whether genotypes of the HTR2C receptor are associated with the metabolic syndrome in patients using antipsychotics. Patients were identified from a schizophrenia disease management program. In this program, patients' blood pressure, triglycerides, high-density lipoprotein-cholesterol, and waist circumference are measured regularly during follow-up. The primary end point of our study was the prevalence of the metabolic syndrome as classified by a modified version of the National Cholesterol Education Program's Adult Treatment Panel III. Primary determinants were polymorphisms in the HTR2C receptor gene (HTR2C:c.1-142948[GT]n, rs3813928 [-997 G/A], rs3813929 [-759 C/T], rs518147 [-697 G/C], and rs1414334 [C > G]). The included patients (n = 112) mainly (>80%) used atypical antipsychotics (clozapine, olanzapine, and risperidone). Carriership of the variant alleles of the HTR2C polymorphisms rs518147, rs1414334, and HTR2C:c.1-142948(GT)n was associated with an increased risk of the metabolic syndrome (adjusted odds ratio [OR], 2.62 [95% confidence interval {CI}, 1.00-6.85]; OR, 4.09 [95% CI, 1.41-11.89]; and OR, 3.12 [95% CI, 1.13-8.16]), respectively. Our findings suggest that HTR2C genotypes are associated with antincreased risk of metabolic syndrome in patients taking antipsychotics.
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PMID:The association between HTR2C gene polymorphisms and the metabolic syndrome in patients with schizophrenia. 1763 16

People with schizophrenia are at greater risk of obesity, Type 2 diabetes, dyslipidaemia and hypertension than the general population. This results in an increased incidence of cardiovascular disease (CVD) and reduced life expectancy, over and above that imposed by their mental illness through suicide. Several levels of evidence from data linkage analyses to clinical trials demonstrate that treatment-related metabolic disturbances are commonplace in this patient group, and that the use of certain second-generation antipsychotics may compound the risk of developing the metabolic syndrome and CVD. In addition, smoking, poor diet, reduced physical activity and alcohol or drug abuse are prevalent in people with schizophrenia and contribute to the overall CVD risk. Management and minimization of metabolic risk factors are pertinent when providing optimal care to patients with schizophrenia. This review recommends a framework for the assessment, monitoring and management of patients with schizophrenia in the UK clinical setting.
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PMID:Minimising metabolic and cardiovascular risk in schizophrenia: diabetes, obesity and dyslipidaemia. 1765 24

Patients with chronic mental illness have multiple health care needs. These patients, particularly those with schizophrenia, have higher incidences of heart disease and metabolic syndrome than the general population and show increased risks of infectious disease, pulmonary disease, and substance abuse. In order to effectively monitor and treat these patients, psychiatric and general health care should be integrated as much as possible. This presentation describes the role of the psychiatrist in helping to maintain the physical health of his or her patients, including monitoring for weight gain and other cardiac risk factors that may be increased by psychotropic medications, and explains the importance of communication between psychiatrists and primary care physicians.
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PMID:Integrating general health care in private community psychiatry practice. 1768 30

Coronary heart disease (CHD) is a major cause of mortality in people who have schizophrenia, and it is caused by many factors relating to lifestyle choices, antipsychotic treatment, and other medical comorbidities. This article focuses on modifiable risk factors such as cigarette smoking, diabetes, hyperlipidemia, hypertension, and the metabolic syndrome, all of which occur more frequently in patients who have schizophrenia than in the general population. Although treatment of risk factors for CHD is still far from ideal, all attempts should be made to strive for wellness to improve patients' long-term outcomes.
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PMID:Reaching for wellness in schizophrenia. 1772 32

Schizophrenic patients who are treated with antipsychotics, especially second generation antipsychotics, such as clozapine and olanzapine, manifest an increase in cholesterol and triglycerides as well as other changes associated with diabetes or the metabolic syndrome. Previous studies have shown that polymorphisms in several genes that regulate lipid metabolism can influence the levels of these lipids and response to drug treatment. We have investigated in an exploratory study whether polymorphisms in the apolipoprotein C-III (ApoC3), apolipoprotein A-V gene (ApoA5) and lipoprotein lipase genes influence differential lipid response to treatment with three second generation antipsychotics-olanzapine, clozapine and risperidone-or treatment with a first generation antipsychotic. A total of 189 patients with schizophrenia or schizoaffective disorder who were being treated with a single antipsychotic were studied in a cross-sectional study design in which fasting serum cholesterol and triglycerides and selected single-nucleotide polymorphosms (SNPs) in the three lipid metabolism genes were assessed. The treatment with antipsychotic monotherapy makes drug haplotype ascertainment less complex. Our analyses showed several nominally significant drug x gene and drug x haplotype interactions. The rarer C allele or the ApoA5_1131 (T/C) SNP was associated with higher cholesterol levels in patients treated with first generation antipsychotics and lower cholesterol levels in patients treated with olanzapine or clozapine. The rarer C allele of the ApoA5_SW19 (G/C) SNP was associated with higher cholesterol in risperidone-treated patients. An ApoA5 CG haplotype was associated with decreased cholesterol in olanzapine- or clozapine-treated patients and higher cholesterol in patients treated with first generation antipsychotics. The presence of the rarer T allele of the ApoC3_1100 (C/T) SNP or the presence of the ApoC3 TG haplotype was associated with decreased triglyceride levels in patients treated with olanzapine or clozapine and a nonsignificant trend for increased triglycerides in patients treated with first generation antipsychotics. The presence of the ApoC3 CC haplotype was associated with increased triglycerides in patients treated with olanzapine or clozapine. The overall magnitude of the effects was not large. These results provide a potential initial step toward a pharmacogenetic approach to selection of antipsychotic treatment which may help minimize the side effect of increases in serum lipids.
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PMID:Allelic variation in ApoC3, ApoA5 and LPL genes and first and second generation antipsychotic effects on serum lipids in patients with schizophrenia. 1772 53

The glutamatergic system has been implicated in neuropsychiatric disorders, such as schizophrenia, bipolar disorder and Alzheimer's disease, which also have a high prevalence of metabolic syndrome. Treatment with ketamine, a non-competitive glutamate N-methyl-d-aspartic acid (NMDA) receptor antagonist, is known to have paradoxical effects of neuroprotection and neurotoxicity. We investigated gene expression in brain tissue of adult mice treated with ketamine to characterize the expression profiles and to identify the affected metabolic pathways. Adult male mice were treated by a single intraperitoneal (i.p.) injection of either s(+)ketamine (80 mg/kg) or distilled water (as the control). Fifty genes were differentially expressed in ketamine-treated mouse brains compared with control mice using oligonucleotide microarray analysis, and the expression of Troponin T1 (Tnnt1) gene was consistently elevated (2- to 4-fold) (p<0.001). Ketamine-induced Tnnt1 expression was confirmed and characterized using RNA in situ hybridization techniques in paraffin embedded brain tissue sections. Tnnt1 expression was induced in the granule layer of the hippocampus, amygdala, hypothalamus, Purkinje cells of cerebellum (p<0.0001), and cerebral cortex. Tnnt1 gene is known to interact directly with FoxO1, which is involved in multiple peripheral metabolic pathways and central energy homeostasis. Our findings suggest that the induction of Tnnt1 gene expression in adult mouse brains by ketamine may illustrate the genes involved in the metabolic syndromes observed in neuropsychiatric disorders.
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PMID:The expression of Troponin T1 gene is induced by ketamine in adult mouse brain. 1785 Jul 69

Patients with mental illnesses such as schizophrenia and bipolar disorder have an increased prevalence of metabolic syndrome and its components, risk factors for cardiovascular disease and type 2 diabetes. Although the prevalence of obesity and other risk factors such as hyperglycemia are increasing in the general population, patients with major mental illnesses have an increased prevalence of overweight and obesity, hyperglycemia, dyslipidemia, hypertension, and smoking, and substantially greater mortality, compared with the general population. Persons with major mental disorders lose 25 to 30 years of potential life in comparison with the general population, primarily due to premature cardiovascular mortality. The causes of increased cardiometabolic risk in this population can include nondisease-related factors such as poverty and reduced access to medical care, as well as adverse metabolic side effects associated with psychotropic medications, such as antipsychotic drugs. Individual antipsychotic medications are associated with well-defined risks of weight gain and related risks for adverse changes in glucose and lipid metabolism. Based on the medical risk profile of persons with major mental illnesses, and the evidence that certain medications can contribute to increased risk, screening and regular monitoring of metabolic parameters such as weight (body mass index), waist circumference, plasma glucose and lipids, and blood pressure are recommended to manage risk in this population. Treatment decisions should incorporate information about medical risk factors in general and cardiometabolic risk in particular. In addition to the implications for individual clinicians, the problem of disparity in meeting healthcare needs for persons with mental illness in comparison with the general population has become an important public policy concern, with recent recommendations from the National Association of State Mental Health Program Directors and the Institute of Medicine. This article provides an overview of cardiometabolic risk in patients with major mental illness and describes steps for risk reduction.
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PMID:Metabolic syndrome and mental illness. 1804 78


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