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

Metabolic abnormalities occur frequently in patients treated with antipsychotics and are of growing concern to clinicians. This study sought to determine whether antipsychotic-associated metabolic abnormalities identified through intensive monitoring can be reversed by switching to aripiprazole. Recent evidence suggests that aripiprazole may exhibit a favorable metabolic safety profile. The study population is a subset of a large (n > 500) ongoing prospective cohort. Thirty-one consecutive patients with schizophrenia who were started on aripiprazole were included in the study. All patients underwent an extensive metabolic evaluation, including an oral glucose tolerance test, at baseline, at 6 weeks, and at 3 months post switch. Metabolic abnormalities were defined as any of the following: new onset diabetes, impaired fasting glucose, impaired glucose tolerance, metabolic syndrome (MetS) according to various definitions, and dyslipidemia. After 3 months of treatment with aripiprazole (mean daily dose 16.3 mg), there was a significant decrease in body weight, body mass index, and waist circumference. There was a significant reduction in fasting glucose, fasting insulin, insulin resistance index, and serum lipids levels (cholesterol, triglycerides, low-density lipoprotein (LDL), LDL/HDL, Chol/HDL, and non-HDL cholesterol). There was also a significant reduction in prolactin levels. All 7 cases of recent onset diabetes were reversed at 3 months follow-up. The MetS was reversed in 50% of patients at 3 months follow-up. Our results support the reversibility of recent onset diabetes on antipsychotic medication when detected early and followed by a switch to aripiprazole.
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PMID:A case series: evaluation of the metabolic safety of aripiprazole. 1694 Mar 38

The accidental discovery (in the 1950s) and subsequent development of antipsychotic drugs have revolutionized the care of many patients with the schizophrenic psychoses. The first-generation antipsychotics, though effective for hallucinations, delusions, as well as a treatment of the disorder in two-thirds of patients with schizophrenia, burdened many patients with extrapyramidal effects (EPS), including dystonias, akathisia, and pseudo-Parkinsonian morbidity. Moreover, they had little or no effect on the most disabling, core symptoms associated with withdrawal of interests and interpersonal relationships. The second-generation antipsychotics, which began to appear in the late 1980s with the introduction of clozapine, had strikingly less morbidity, contributing little or no EPS and providing at least modest promise of reduction of negative symptoms and enhancement of some aspects of cognition. However, some second-generation antipsychotics have induced considerable weight gain, and appear to lower the threshold for the development of the metabolic syndrome, which increases cardio-vascular morbidity. The actual mechanism(s) of action of the antipsychotic drugs is still in dispute. Direct and indirect effects on dopamine transmission have been supported by much of the evidence. Direct blockade of dopamine hyperactivity and partial restoration deficient dopamine has been the standard explanation of their effects. However, dysfunctional intracellular signal transduction and dysfunction of myelin are emerging as competing pathologies upon which antipsychotics act. It is likely that the next generation of antipsychotics will act more directly and more specifically on such underlying neuropathology.
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PMID:Evolution of antipsychotic intervention in the schizophrenic psychosis. 1701 96

The introduction of second-generation antipsychotic drugs for the treatment of schizophrenia has provided significant benefits for clients experiencing this disorder. While they have been found effective in reducing psychotic symptoms, there is evidence that these drugs are also linked with a group of side effects commonly known as the metabolic syndrome. Mental health nurses are well positioned to prevent, detect and/or manage the development of this problematic constellation of symptoms. Guidelines for practice can be useful in prevention and management of the syndrome and enhance nursing care of clients who are taking second-generation antipsychotics.
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PMID:The metabolic syndrome and schizophrenia: the latest evidence and nursing guidelines for management. 1708 76

Mortality rates in patients with schizophrenia are double compared with the general population, with cardiovascular disease causing 50% of the excess. Lowering low-density lipoprotein cholesterol is recognized as a primary target for the prevention of cardiovascular mortality. The effects of lipid-lowering treatment were evaluated in patients with schizophrenia. Forty-six patients with schizophrenia and with severe dyslipidaemia were identified. All were treated with antipsychotics. Patients were screened for cardiovascular risk factors and examined at baseline when statin therapy was initiated. The effects of lipid-lowering medication on lipid profile, glucose homeostasis and components of metabolic syndrome were evaluated at 3 months follow-up. After 3 months of statin therapy, a significant decrease in triglycerides, total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and, in associated ratios, low-density lipoprotein/high-density lipoprotein, cholesterol/high-density lipoprotein was observed. No significant changes occurred in high-density lipoprotein cholesterol, body mass index, waist circumference or glucose homeostasis. The only component of metabolic syndrome affected by statin therapy has been the serum triglyceride level. Statins proved effective in the management of dyslipidaemia in patients with schizophrenia treated with antipsychotics. More complex treatment may be required for associated metabolic disturbances.
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PMID:Pharmacological treatment of severe dyslipidaemia in patients with schizophrenia. 1715 59

Compared with the general population, persons with schizophrenia have up to a 20% shorter lifespan, with cardiovascular disease as the leading cause of death. In addition, persons with schizophrenia have increased prevalence of the metabolic syndrome (obesity, insulin resistance, dyslipidemia, impaired glucose tolerance, and hypertension), increased prevalence of risk factors such as smoking, poverty, and poor nutrition, and reduced access to medical care. Results from the recent Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) provide further evidence of the metabolic risk associated with different atypical antipsychotics. Based on this study and a growing number of other randomized clinical trials, clozapine and olanzapine treatment can produce substantial mean changes in weight and an increased risk of associated metabolic disturbances. Risperidone and quetiapine treatment can produce intermediate changes in mean weight in comparison to treatment with other atypical antipsychotics, with discrepant results with respect to metabolic risk. Aripiprazole and ziprasidone treatment induced the lowest mean changes in weight gain and had no effect on risk for adverse metabolic changes, among currently available atypical agents. Considerable evidence indicates that mentally ill patients often do not receive adequate recognition of, monitoring of, or care for their medical illnesses. There is a critical need for psychiatrists and primary care professionals to increase awareness of and attention to the physical health problems of persons with mental illness, including appropriate management of metabolic adverse events associated with psychiatric medications.
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PMID:Metabolic considerations in the use of antipsychotic medications: a review of recent evidence. 1728 24

It is well recognized that investigation into the relationship between early life programming and subsequent neurological disorders may have powerful implications for understanding the human vulnerability to psychopathology. The present article will propose that schizophrenia may be adaptively programmed by early environmental adversity permitting physiological and behavioral characteristics that would have created a fitness advantage in the ancestral environment under conditions of nutritional scarcity and severe environmental stress. This proposition will be analyzed in terms of phenotypic plasticity theory which explains how and why specific environmental stressors can alter normal gene expression resulting in an alternative phenotype that is better suited for an adverse environment. The primary neurophysiological symptoms of schizophrenia can be induced in animals through exposure to prenatal and postnatal stressors, and that schizophrenia itself is known to be associated with exposure to stress during development, supports the view that the "disorder" may represent a predictive, adaptive response to adversity. In fact, maternal malnutrition, maternal stress, multiparity, short birth interval and stress provoking postnatal events are well recognized epidemiological risk factors for schizophrenia that may represent cues for the initiation of epigenetic programming. Behavioral and physiological characteristics of schizophrenia will be analyzed and interpreted as protective in the context of environmental hardship. For instance, the hypometabolic areas of the schizophrenic brain--the hippocampus and the frontal lobes--are the same areas that are known to become adaptively hypometabolic in response to starvation, stress and variations in ecological rigor in birds and mammals. Individuals with schizophrenia are also highly genetically inclined to develop the metabolic syndrome, which is widely thought to allow developmentally deprived mammals to conserve energy under poor circumstances. It is well known that schizophrenia features an up-regulated hypothalamic-pituitary-adrenal axis and an exaggerated stress response--both alterations thought to represent predictive, adaptive responses to stress in mammals--which may have increased attentiveness to the environment and created a defensive, vigilance-based behavioral strategy. The habituation deficits characteristic of schizophrenia--which can be induced in other mammals through stress--may represent a cognitive strategy that alerts the organism to salient, potentially informative stimuli and that permits it to be more impulsive and vigilant. Inability to calm instinctual drives, ignore arousing stimuli, and inhibit transient desires are all core characteristics of the disorder, which predict social and vocational disabilities in modern times, but may have amounted to a robust, selfish strategy in prehistoric times.
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PMID:Schizophrenia and phenotypic plasticity: schizophrenia may represent a predictive, adaptive response to severe environmental adversity that allows both bioenergetic thrift and a defensive behavioral strategy. 1732 Oct 61

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.
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PMID:Abnormal glucose metabolism in patients treated with antipsychotics. 1741 28

Metabolic syndrome is a risk factor for cardiovascular disease. People with chronic schizophrenia are at risk for metabolic syndrome because of their diets, lifestyle, and (in some cases) their medication. The increased risk of metabolic syndrome has implications for the delivery of care to this population. This article provides an overview of metabolic syndrome in patients with schizophrenia and evidence-based criteria for monitoring this population. A recommendation is made to aggregate data collection in one place to facilitate follow-up. A sample form and letter are provided.
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PMID:Evidence-based monitoring for metabolic syndrome in clients with chronic schizophrenia. 1746 71

Individuals with serious mental illness experience excess morbidity and mortality, including an increased prevalence of diabetes mellitus and cardiovascular disease. Cardiovascular disease is the leading cause of death in persons with serious mental illness, and the elevated prevalence of obesity in this population is of particular concern. Obesity is an independent cardiometabolic risk factor that impacts morbidity and mortality and contributes to the development of other cardiometabolic risk factors, such as dyslipidemia and hypertension. In addition, obesity is a major risk factor for type 2 diabetes, with the relative risk of diabetes increasing with body mass index. Increased abdominal fat is strongly associated with insulin resistance, which can lead to impaired glucose regulation. Abdominal obesity, hyperglycemia, hypertension, and dyslipidemia are key components of the metabolic syndrome, a constellation of cardiometabolic risk factors linked by their common association with insulin resistance. Evidence from large clinical samples indicates a high prevalence of metabolic syndrome and all of its components in persons with serious mental illness, particularly in patients with schizophrenia. In addition, psychotropic agents, including some antipsychotic medications, are associated with substantial weight gain, as well as with adiposity-dependent and possibly adiposity-independent changes in insulin sensitivity and lipid metabolism, which increase the risk of diabetes and cardiovascular disease. Among the second-generation antipsychotics, clozapine and olanzapine are associated with the highest risk of substantial weight gain, similar to the weight gain potential associated with low-potency first-generation antipsychotics such as thioridazine or chlorpromazine, as well as with an increased risk of diabetes and dyslipidemia. Various strategies for monitoring cardiometabolic risk factors in patients with mental illness are discussed in this review.
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PMID:Antipsychotic medications: metabolic and cardiovascular risk. 1753 94

It has long been known that psychiatric patients experience increased morbidity and mortality associated with a range of physical disorders. Lifestyle, inadequate health care, and a variety of other factors all contribute to the poor physical health of people with severe mental illness. Second-generation antipsychotics have gained widespread acceptance for the management of patients with schizophrenia and other forms of severe mental illness. While demonstrating several advantages over first-generation antipsychotics, second-generation antipsychotics have been found to cause or exacerbate several metabolic disorders, including diabetes, obesity, dyslipidemia, and metabolic syndrome. These disorders are closely linked and consistently associated with the development of cardiovascular disease, with varying prevalence rates depending on the second-generation antipsychotic used. As a result, several authoritative guidelines have been developed for the monitoring and management of metabolic disturbances in schizophrenia and other forms of severe mental illness. Specifically, the guidelines and recommendations generated from the Mount Sinai Conference on Medical Monitoring and the American Diabetes Association/American Psychiatric Association Consensus Development Conference on Antipsychotic Drugs and Obesity and Diabetes call for a more integrated and cooperative approach between primary care physicians and mental health care providers to improve the quality of health care for people with severe mental illness. By routinely performing physical health monitoring, referrals, and/or treatment for patients with schizophrenia and other forms of severe mental illness, mental health care providers can take a lead role in transforming the current system of fragmented mental and physical health services into a system focused on early intervention, wellness, and recovery.
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PMID:Implementation of monitoring and management guidelines for second-generation antipsychotics. 1753 95


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