Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Psychiatric disorders themselves and treatment with conventional antipsychotic medications have in a number of early studies been associated with venous thromboembolism. In general, information on the relationship between antipsychotics and this possible adverse effect is in the form of case reports and open cross-sectional studies. However, recently the association between conventional antipsychotics and venous thrombosis has been strengthened as a result of the publication of a large, nested, case-control study. In this study, low-potency antipsychotic drugs were more strongly associated with venous thrombosis than high-potency drugs. In addition, recent epidemiological data support an association between the atypical antipsychotic agent clozapine and venous thromboembolism. The risk for venous thromboembolism seems to be highest during the initial months of treatment with antipsychotics. The biological mechanisms responsible for this possible adverse drug reaction are unknown, but a number of hypotheses have been suggested. The increased risk may be the result of drug-induced sedation, obesity, hyperleptinaemia, antiphospholipid antibodies and increased activity in the coagulation system. The association could also be related to underlying risk factors present in patients with psychosis such as smoking. Despite the limitations of present knowledge, clinicians should be aware of this possible adverse drug reaction and should consider interrupting or changing the antipsychotic regimen in patients in whom this reaction is suspected. More studies are needed in order to further elucidate this adverse effect, particularly to determine the incidence rate, possible predisposing factors and the biological mechanisms involved.
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PMID:Antipsychotic-induced venous thromboembolism: a review of the evidence. 1238 32

Anti-psychotic medications are an important therapeutic option for many individuals with schizophrenia. Recently, a growing interest has been observed on weight gain, which is now a well-known adverse effect of many anti-psychotics. As obesity is frequently a comorbid condition with schizophrenia, patients with schizophrenia are inherently at increased risk of developing obesity-related conditions such as cardiovascular disease and type 2 diabetes. The consequences of excessive weight gain (obesity) associated with anti-psychotic drugs are likely to include adverse effects on health, social burden and poor compliance or even discontinuation of therapy by the patients. In this article, we focus on different aspects of weight gain induced by anti-psychotics. This review comprises the following sections: (i) the pharmacological basis of anti-psychotic-induced weight gain and metabolic effects with a review of all anti-psychotics that can be used in patients with schizophrenia; (ii) the clinical impact of the body weight gain (morbidity, psychatric consequences, mortality); (iii) the management of obesity (identification of risk factors including pharmacogenetics, diet, behavioural therapies, pharmacological approach). An understanding of these aspects is important for those who prescribe anti-psychotics in order to provide the patient the best therapeutic management.
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PMID:Weight gain profiles of new anti-psychotics: public health consequences. 1291 14

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

Platelet activation is involved in the pathogenesis of atherosclerosis and venous thromboembolism, and might therefore be a possible link between the two entities. Prolactin and leptin have recently been recognized as potent co-activators of ADP-dependent platelet aggregation or P-selectin expression, and are therefore suspected as additional risk factors for both arterial and venous thrombosis. There are clinical situations that have a known association with higher prolactin or leptin levels (pregnancy, obesity or anti-psychotic therapy) and increased risk of thromboembolic events. We compared the impact of both hormones on platelet activation in vitro and in vivo, indicating that prolactin has a stronger effect on platelet activation as leptin in vitro and in vivo. We have also demonstrated that prolactin levels are increased in so called idiopathic thrombosis, and that conversely, patients with prolactinoma have an increased frequency of thrombosis during the hyperprolactinemic state, in a retrospective analysis. Moreover, we have demonstrated increased prolactin values in stroke and myocardial infarction. Prospective studies have yet to be performed to give this theory its final confirmation. The involvement of hormonal factors in platelet aggregation and venous or arterial thrombosis may have important clinical implications such as for risk stratification of patients with venous and arterial thrombosis or new therapeutic options such as decreasing pro-coagulant hormone levels in certain risk situations.
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PMID:Co-activation of platelets by prolactin or leptin--pathophysiological findings and clinical implications. 1498 99

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

Hormones such as prolactin and leptin have recently been recognized as potent platelet aggregation co-activators, and have therefore been postulated as an additional risk factor for both arterial and venous thrombosis. Clinical situations exist that are known to be associated with higher leptin and/or prolactin levels (obesity, pregnancy, prolactinomas and anti-psychotic therapy respectively) and increased venous thrombosis or atherosclerosis risk. Therefore, we compared the impact of both hormones on platelet activation in vitro and in vivo. First, we investigated platelet aggregation and P-selectin expression after stimulation with 1,000 mU/l prolactin or 100 ng/ml leptin in five healthy volunteers in vitro. Prolactin revealed significant higher levels of P-selectin expression and platelet aggregation than leptin in all subjects. We also compared the correlation of prolactin and leptin values with the P-selection expression on platelets. Previously, we detected a significant correlation between prolactin values and ADP-stimulated P-selectin expression on platelets in pregnant women, patients with pituitary tumours, and patients on anti-psychotic therapy. In contrast, leptin did not correlate with P-selectin expression in all subject groups investigated. However, leptin correlated with body mass index in the subjects investigated. Our data indicate that prolactin has a stronger effect on platelet activation as leptin in vitro and in vivo. Moreover, our data suggest that the stronger effect of prolactin on ADP-stimulated platelet aggregation, compared to leptin, depends on higher stimulation of CD62p expression by prolactin.
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PMID:Differences in platelet activation by prolactin and leptin. 1530 27

BACKGROUND: Since the introduction of the first atypical antipsychotics in the early 1990s, this class of medication has been increasingly relied upon for the treatment of a variety of patients with psychotic and mood disorders.DATA SOURCES: The following retrospective review was derived from the MEDLINE database using the search terms metabolic syndrome, insulin resistance, obesity, diabetes, severe mental illness, schizophrenia, bipolar disorder, mood disorders, depression, unipolar depression, and prevalence from 1966 to the present. LITERATURE SYNTHESIS: Coincident with the growing usage of these agents, there have been a growing number of literature reports of changes in metabolic homeostasis among patients taking these medications. These changes have led to interest in evaluating whether there is a relationship among these mental illnesses, their psychiatric treatments, and certain physical comorbidities known collectively as the metabolic syndrome. This article reviews the existing literature around the metabolic syndrome in patients with severe mental illnesses. CONCLUSION: Patients with severe mental illnesses, particularly schizophrenia and chronic mood disorders, demonstrate a higher prevalence of metabolic syndrome or its components compared with the general population. Based upon this increased risk in these patients, baseline and periodic medical evaluations should become a standard component in ongoing clinical assessment.
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PMID:The Metabolic Syndrome in Patients With Severe Mental Illnesses. 1536 18

In this research psychic and somatic symptoms related to disturbances of hypothalamus-hypophysis-peripheral regulation which may occur in the schizophrenic process were analysed. Authors discussed the problem of relations between hypothalamus neuroregulation and pathogenesis of endocrine disturbances which suggest the organic cause of obesity, hirsutism and secondary amenorrhea among women diagnosed with paranoid schizophrenia. Actual antipsychotic pharmacological treatment, including some side-effects: the metabolic (obesity) and the endocrine (hyperprolactinemia) ones were considered. The authors conclude that endocrine disorders which are connected with hypothalamus disfunction (sleeping, eating and reproductive functions) may reach the psychotic symptoms and treating them influences at the same time some endocrine changes. The estimation of PRL release in a test of stimulation with metoclopramide can be a sensitive (though not specific) test of dopaminergic activity in tuberous--infundibulum pathway and may be used to control the treatment.
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PMID:[The endocrine mask of a developing process of schizophrenia--case study]. 1552 34

Obesity and attention-deficit hyperactivity disorder (ADHD) are both increasing in prevalence. Childhood exposure to television has shown linkage to both ADHD and obesity with the former ascribed to dysfunctional cognitive hyperstimulation and the latter to altered patterns of diet and exercise. Empirical evidence has contradicted prior presumptions that the hyperactivity of ADHD would decrease the risk of obesity. Instead, obesity and ADHD demonstrate significant comorbidity. We propose that obesity and ADHD represent different manifestations of the same underlying dysfunction, a phenomenon we term environmental oversampling syndrome. Oversupply of information in the form of nutritional content and sensory content may independently predispose to both obesity and ADHD. Moreover, the pathogenic mechanisms of these conditions may overlap such that nutritional excess contributes to ADHD and cognitive hyperstimulation contributes to obesity. The overlapping effects of medications provide further evidence towards the existence of shared etiologic pathways. Metabolism and cognition may represent parallel systems of intelligence, and oversampling of content may constitute the source of parallel dysfunctions. The emerging association between psychiatric and metabolic disorders suggests a fundamental biologic link between these two systems. In addition, the immune system may represent yet another form of intelligence. The designation of syndrome X subsumes seemingly unrelated metabolic and inflammatory entities. Environmental oversampling syndrome may represent an even more inclusive concept that encompasses various metabolic, inflammatory, and behavioral conditions. Apparently disparate conditions such as insulin resistance, diabetes, hypertension, syndrome X, obesity, ADHD, depression, psychosis, sleep apnea, inflammation, autism, and schizophrenia may operate through common pathways, and treatments used exclusively for one of these conditions may prove beneficial for the others.
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PMID:Obesity and ADHD may represent different manifestations of a common environmental oversampling syndrome: a model for revealing mechanistic overlap among cognitive, metabolic, and inflammatory disorders. 1590 45

Patients treated with atypical antipsychotic drugs commonly gain excess weight. Because obesity is associated with considerable morbidity and decreased life expectancy, treatment of weight gain in these patients is critical. Topiramate, a fairly new anticonvulsant, promotes bodyweight loss in healthy obese subjects, patients with bipolar disorder, and patients with eating disorder. However, there are very few reports about the efficacy of topiramate for weight management in schizophrenic patients. We present the cases of three Taiwanese patients with schizophrenia whose bodyweight increased as a result of atypical antipsychotics treatment, then was controlled by topiramate without aggravation of their psychotic symptoms.
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PMID:Management of atypical antipsychotic-induced weight gain in schizophrenic patients with topiramate. 1619 68


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