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

Many antipsychotic drugs disturb the regulation of glucose metabolism in patients treated for schizophrenia. The goal of the present studies was to determine if these antipsychotic drugs produce hyperglycemia in mice in relation to their ability to interfere with glucose uptake and utilization. Male C57BL/6 mice were injected with a panel of typical and atypical antipsychotic drugs and blood glucose levels were determined periodically over a 3- to 6-h time interval. The atypical drugs, clozapine, desmethylclozapine, quetiapine, and loxapine, and the original antipsychotic, chlorpromazine, induced significant hyperglycemia in the mice in accordance with their effects on glucose transport. By contrast, haloperidol and sulpiride, which have little effect on glucose uptake, did not induce hyperglycemia. Risperidone produced a modest elevation of blood glucose levels, but only at a low dose of the drug. Cytochalasin B, a specific inhibitor of the glucose transporter (GLUT) protein, produced significant hyperglycemia in the mice. Overall, there was a strong correlation between the ability of a drug to inhibit glucose transport in vitro and its ability to induce hyperglycemia in vivo. Finally, the drugs that produced hyperglycemia in mice have been linked to the development of diabetes in patients.
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PMID:Induction of hyperglycemia in mice with atypical antipsychotic drugs that inhibit glucose uptake. 1287 13

Diabetes or hyperglycemia associated with the use of atypical anti-psychotic agents is a subject of growing concern among health care providers and the patients who use the drugs. Although much attention has been relegated to this topic in the mental health literature, there has been little attention devoted to it in the diabetes literature. The purpose of this report is to review the problem of diabetes mellitus associated with atypical anti-psychotic use from an endocrinology perspective. This paper will specifically present (a) a review of the increased prevalence of diabetes in the setting of schizophrenia, (b) a compilation and critical assessment of the existing publications that have documented the association of hyperglycemia and atypical anti-psychotic use, (c) a discussion of the potential mechanisms through which antipsychotics may lead to disturbances in glucose homeostasis, and (d) recommendations for the effective monitoring and treatment of affected patients.
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PMID:Diabetes mellitus associated with atypical anti-psychotic medications. 1451 22

With the widespread use of atypical antipsychotics over the past several years, adverse metabolic effects have emerged as the most serious medical consequences of pharmacotherapy with some of these agents. Initially, weight gain and obesity were observed (especially with clozapine and olanzapine), but subsequently, type 2 diabetes and dyslipidemia became apparent as well. Further, many reports suggest that sudden and severe (occasionally fatal) diabetes ketoacidosis (DKA) can emerge during treatment with some atypical antipsychotics, even in the absence of adiposity. A marked increase of serum lipids (especially triglycerides) has also been reported, to varying degrees, with different atypicals. This article reviews the data regarding metabolic dysfunction in patients with psychosis (schizophrenia and bipolar disorder). Populations with psychosis have a 2-3-fold higher prevalence of diabetes even before treatment with any antipsychotics, suggesting a possible genetic linkage or comorbidity; this was confirmed with glucose regulation studies in schizophrenia and mania. The induction of type 2 diabetes with atypicals has further increased the prevalence of noninsulin-dependent diabetes from about 6% to 8% to 11% to 15% according to recent studies, and even higher rates of subclinical hyperglycemia. Serious weight gain (eg, 26-29 lbs after 1 year of clozapine or olanzapine treatment) is an important risk factor, but sudden DKA has now been reported in patients with minimal weight gain, suggesting alternative mechanisms, such as insulin resistance, as a direct effect of some atypicals. Psychiatrists can reduce the risk of metabolic disorders in schizophrenia and bipolar disorder by avoiding the use of certain atypicals as first-line treatment in patients with a personal or family history of diabetes, obesity, and hyperlipidemias. Regulatory agencies in some countries have already taken action in this regard.
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PMID:Factors in antipsychotic drug selection: tolerability considerations. 1497 55

The antipsychotic drugs (APDs) are fundamental tools in current psychiatric practice. A new generation of agents, the atypical APDs, represents an important progress in the treatment of psychotic disorders. Unfortunately, some of them induce excessive body weight gain (BWG), obesity, hyperglycemia and dyslipidemia in the following order: clozapine approximately equal to olanzapine > quetiapine > risperidone > ziprasidone = aripiprazole. Appetite stimulation is probably the main mechanism of BWG and this is strongly correlated with the APD affinity for H1 (histaminergic) and alpha1 (adrenergic) receptors. A composed ratio of the APD affinity for diverse neurotransmitters involved in food intake (FI) regulation correlates with BWG as well. Endocrine/metabolic mechanisms, such as the activation of the hypothalamus-pituitary-adrenal axis, changes in insulin sensitivity (by conventional and atypical agents), hyperprolactinemia and gonadal dysfunction (by conventional APDs and risperidone) may also be involved. Importantly, patients with schizophrenia may have a genetically-based predisposition to appetite dysregulation, insulin resistance and endocrine imbalance involving gonadal steroids. Excessive BWG must be prevented or attenuated by proper drug selection, combining or switching agents, nutritional assistance and physical exercise. Amantadine. metformin and reboxetine proved to significantly lessen APD-induced BWG. Notwithstanding this, novel strategies are necessary to treat this side effect in a clinical population particularly prone to poor compliance and under a high risk of negative drug interaction.
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PMID:Drug induced weight gain, an impediment to successful pharmacotherapy: focus on antipsychotics. 1505 13

The introduction of atypical antipsychotic drugs has provided a clear benefit for many schizophrenia patients, with less risk for the extrapyramidal side effects associated with conventional antipsychotics. However, some antipsychotics are associated with an increased risk of adverse metabolic outcomes, including weight gain, dyslipidemia, and hyperglycemia. Increases in adiposity and disturbances in glucose and lipid metabolism represent a serious health risk in a patient that may be predisposed to these metabolic conditions. The increased risk for diabetes with certain antipsychotics may be associated with the risk of treatment-induced weight gain. However, other mechanisms, including effects on central neurotransmitters and direct effects on glucose metabolism, may contribute to the development of disordered glucose metabolism. The purpose of this article is to review the association between antipsychotic medications and obesity, insulin resistance, and diabetes, including the mechanisms through which these changes might be effected.
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PMID:Abnormalities of glucose metabolism associated with atypical antipsychotic drugs. 1560 Mar 83

Atypical antipsychotics, like clozapine, have fewer extrapyramidal side effects compared with typical antipsychotics, however, such treatment is associated with several adverse metabolic effects such as weight gain, hyperglycemia and hyperlipidemia in patients with schizophrenia. In this study, we investigated the effects of 30-day clozapine treatment on weight change, and serum fasting glucose, cholesterol and triglyceride levels in male BALB/c mice. The results demonstrate that 10.0 mg/kg clozapine group gained significantly less weight but had higher cholesterol compared with controls and the 2.0 mg/kg clozapine group. Our findings indicate the possibility of using mice to study the mechanisms of body weight change and lipid dysregulations induced by clozapine.
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PMID:Effects of subchronic clozapine administration on serum glucose, cholesterol and triglyceride levels, and body weight in male BALB/c mice. 1573 41

Antipsychotic medications are a mainstay in the treatment of schizophrenia and are widely used in other psychiatric conditions. New generation antipsychotic agents (NGAs) are increasingly replacing first generation antipsychotic agents (FGAs), mainly due to a decreased risk for extrapyramidal symptoms, better overall tolerability, as well as some efficacy advantages. However, some of these NGAs are associated with adverse metabolic effects such as substantial weight gain, the induction of insulin resistance and lipid disorders. Among these substances, clozapine and olanzapine induce the most significant weight gain, olanzapine mainly by increasing body fat and both of these antipsychotics have been associated with disturbances in glucose metabolism. Diabetes mellitus induced by treatment with some NGAs occurred in many cases within days to weeks after initiation of SGA therapy, in some cases hyperglycemia promptly resolved after discontinuation of the medication and several reports have documented recurrent hyperglycemia after a rechallenge with the same drug. One possible pathomechanism for hyperglycemia induced by these NGAs is the induction of insulin resistance via humoral and/or cellular pathways. Alternatively, NGA induced diabetes may occur because of weight gain or a change in body fat distribution with a shift to a predominantly visceral fat type or through a direct effect on insulin sensitive target tissues. In this article we like to review the metabolic side effects of NGA treatment, highlight recent advances in the pathogenesis of these metabolic complications and discuss potential treatments of these side effects.
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PMID:[Antipsychotic drug-induced changes in metabolism]. 1679 55

Abnormalities in glucose and lipid regulation have been reported in schizophrenia during antipsychotic medications. The objectives of the present study were to evaluate the effect of various peroxisome proliferator-activated receptor modulators viz. glimepiride, rosiglitazone and fenofibrate on chlorpromazine, clozapine and ziprasidone induced hyperglycemia and hyperlipidemia in mice. Male Swiss albino mice were orally treated with chlorpromazine, clozapine and ziprasidone concurrently with the antidiabetic medications for 7 days. Plasma glucose, insulin and triglyceride levels were determined at the end of the study. Chlorpromazine and clozapine elevated the glucose and triglyceride levels in normal mice, with no effect on insulin but ziprasidone increased the basal triglyceride and insulin levels and did not have any effect on glucose. Glimepiride and rosiglitazone showed beneficial glucose and triglyceride lowering effects in chlorpromazine and clozapine animals and no effect on insulin levels. Fenofibrate significantly reduced the glucose levels only in animals treated with clozapine, and exhibited significant reduction of triglyceride levels in chlorpromazine, clozapine and ziprasidone treated animals. All three antidiabetic/hypolipidemic agents lowered triglyceride and insulin levels in ziprasidone treated animals. The results of the present studies suggest that hyperglycemia, hyperinsulinemia and hypertriglyceridemia induced by various antipsychotics may involve diverse mechanisms.
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PMID:Antipsychotic induced metabolic abnormalities: an interaction study with various PPAR modulators in mice. 1682 8

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

Atypical antipsychotics like olanzapine are more efficacious in treating negative symptoms and have less side effects. Nevertheless, important adverse effects of olanzapine are, for example, weight gain and hyperglycemia. Perazine in combination with carbamazepine has shown satisfying results in several single-schizophrenia patients, leading to the hypothesis of being equal or even superior to atypical antipsychotic monotherapy. The aim of the present study was to survey the hypothesis that perazine in combination with carbamazepine have an outcome and risk of side effects comparable to olanzapine. Eleven patients with DSM-IV schizophrenia received 14.0 +/- 5.0 mg/day olanzapine and 12 patients received 360.0 +/- 196.0 mg/day perazine in combination with 404.0 +/- 229.0 mg/day carbamazepine. Symptoms and neuropsychological state were assessed 3 times (days 0, 7, 21) using the Positive and Negative Syndrome Scale and the Brief Psychiatric Rating Scale. The neuropsychological state was assessed by the following neuropsychological tests: Benton, d2, ZVT, VLMT and MWT-B. Data were analyzed of variance for multiple dependent variables and repeated-measures multivariate analysis of variance. Positive and Negative Syndrome Scale and Brief Psychiatric Rating Scale scores showed superior improvement in the group receiving olanzapine. Olanzapine offers a more favorable response in positive symptoms than does perazine in combination with carbamazepine. The effect on negative symptoms is favorable in both forms of therapy and no significant differences between the groups could be determined. In both groups, treatment was associated with improved performance in cognitive tests; however, no differences were determined in the effects of the drugs. Results suggest that olanzapine offers a better response in positive symptoms than perazine in combination with carbamazepine.
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PMID:Perazine and carbamazepine in comparison to olanzapine in schizophrenia. 1757 Sep 51


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