Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Although physical inactivity is a leading cause of death and the Surgeon General recommends regular moderate physical activity, many Americans are inactive. Because of their increased burden of obesity and diabetes, people with severe mental illness (SMI) especially may benefit from physical activity, yet little is known about the prevalence and types of physical activity in people with SMI. We surveyed outpatients with schizophrenia and affective disorders at two psychiatric centers in Maryland and compared physical activity patterns to an age-gender-race-matched national sample (National Health and Nutrition Examination Survey III) of the general population. We found that people with SMI are overall less physically active than the general population, although the proportion with recommended physical activity levels was equal. The participants with SMI were more likely to walk as their sole form of physical activity. Within the SMI group, those without regular social contact and women had higher odds of being inactive.
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PMID:Physical activity patterns in adults with severe mental illness. 1620 58

Since the discovery of an endogenous cannabinoid system, research into the pharmacology and therapeutic potential of cannabinoids has steadily increased. Two subtypes of G-protein coupled cannabinoid receptors, CB(1) and CB(1), have been cloned and several putative endogenous ligands (endocannabinoids) have been detected during the past 15 years. The main endocannabinoids are arachidonoyl ethanolamide (anandamide) and 2-arachidonoyl glycerol (2-AG), derivatives of arachidonic acid, that are produced "on demand" by cleavage of membrane lipid precursors. Besides phytocannabinoids of the cannabis plant, modulators of the cannabinoid system comprise synthetic agonists and antagonists at the CB receptors and inhibitors of endocannabinoid degradation. Cannabinoid receptors are distributed in the central nervous system and many peripheral tissues, including immune system, reproductive and gastrointestinal tracts, sympathetic ganglia, endocrine glands, arteries, lung and heart. There is evidence for some non-receptor dependent mechanisms of cannabinoids and for endocannabinoid effects mediated by vanilloid receptors. Properties of CB receptor agonists that are of therapeutic interest include analgesia, muscle relaxation, immunosuppression, anti-inflammation, antiallergic effects, improvement of mood, stimulation of appetite, antiemesis, lowering of intraocular pressure, bronchodilation, neuroprotection and antineoplastic effects. The current main focus of clinical research is their efficacy in chronic pain and neurological disorders. CB receptor antagonists are under investigation for medical use in obesity and nicotine addiction. Additional potential was proposed for the treatment of alcohol and heroine dependency, schizophrenia, conditions with lowered blood pressure, Parkinson's disease and memory impairment in Alzheimer's disease.
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PMID:Cannabinoids. 1626 85

Metabolic syndrome is a constellation of clinical findings that identify individuals at higher than normal risk of developing diabetes mellitus or cardiovascular disease. There are two principal definitions, one emerging from the American National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, and the other from the World Health Organization. Both definitions share the common elements of abdominal obesity, hypertriglyceridaemia, low HDL-cholesterol, hypertension and abnormal glucose regulation. The syndrome is relatively common across continents, and also among those without marked obesity. It is even more common among patients with major mental health disorders such as schizophrenia. Metabolic syndrome can be used to assess risk for cardiovascular disorder and death, and is an alternative to Framingham Risk Calculations. C-reactive protein may play an additional role in risk prediction. Ongoing monitoring for all components of the metabolic syndrome is necessary. Individuals at high risk require multimodal interventions, including lifestyle interventions and targeted medications as appropriate.
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PMID:Metabolic syndrome and cardiovascular disease. 1628 Mar 41

A retrospective cohort design was used to study risk factors and cardiovascular end points among adults, with and without psychoses, receiving primary care. Earlier onset of risk factors and heart disease was noted among individuals with schizophrenia compared to those with affective psychoses and no disabilities. Patients with schizophrenia had increased relative risk for obesity, congestive heart failure, dementia, depression and death, while patients with affective psychoses had increased risk for dementia and diabetes.
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PMID:Heart disease, schizophrenia, and affective psychoses: epidemiology of risk in primary care. 1632 87

Weight gain is associated with the use of many psychotropic medications, including antidepressants, mood stabilizers, antipsychotic drugs, and may have serious long term consequences: it can increase health risks, specifically from overweight (BMI = 25-29.9 kg/m2) to obesity (BMI > or =30 kg/m2), according to Body Mass Index (BMI), and the morbidity associated therewith in a substantial part of patients (hypertension, coronary heart desease, ischemic stroke, impaired glucose tolerance, diabetes mellitus, dyslipidemia, respiratory problems, osteoarthritis, cancer); according to patients, psychosocial consequences such as a sense of demoralization, physical discomfort and being the target of substantial social stigma are so intolerable that they may discontinue the treatment even if it is effective. The paper reviews actual epidemiological data concerning drug induced weight gain and associated health problems in psychiatric patients : there is a high risk of overweight, obesity, impaired glucose tolerance, diabetes mellitus, premature death, in patients with schizophrenia or bipolar disorder; and the effects of specific drugs on body weight: Tricyclic Antidepressants (TCA) induced weight gain correlated positively with dosage and duration of treatment, more pronounced with amitriptyline ; Selective Serotonin Reuptake Inhibitors (SSRI) decrease transiently bodyweight during the first few weeks of treatment and may then increase bodyweight; weight gain appears to be most prominent with some mood stabilizers (lithium, valproate); atypical antipsychotics tend to cause more weight gain than conventional ones and weight gain, diabetes, dyslipidemia, seem to be most severe with clozapine and olanzapine. Conceming the underlying mechanisms of drug induced weight gain, medications might interfere with central nervous functions regulating energy balance; patients report about: increase of appetite for sweet and fatty foods or "food craving" (antidepressants, mood stabilizers, antipsychotic drugs) and weight gain despite reduced appetite which can be explained by an altered resting metabolic rate (TCA, SSRI, Monoaminoxidase Inhibitors MAO I). According to current concepts, appetite and feeding are regulated by a complex of neurotransmitters, neuromodulators, cytokines and hormones interacting with the hypothalamus, including the leptin and the tumor necrosis factor system. The pharmacologic mechanisms underlying weight gain are presently poorly understood: maybe the different activities at some receptor systems may induce it, but also genetic predisposition. Understanding of the metabolic consequences of psychotropic drugs (weight gain, diabetes, dyslipidemia) is essential: the insulin-like effect of lithium is known; treatment with antipsychotic medications increases the risk of impaired glucose tolerance and diabetes mellitus. Several management options of weight gain are available from choosing or switching to another drug, dietary advices, increasing physical activities, behavioural treatment, but the best approach seems to attempt to prevent the weight gain : patients beginning maintenance therapy should be informed of that risk, and nutritional assessment and counselling should be a routine part of treatment management, associated with monitoring of weight, BMI, blood pressure, biological parameters (baseline and three months monitoring of fasting glucose level, fasting cholesterol and triglyceride levels, glycosylated haemoglobin). Psychiatrics must pay attention to concomitant medications and individual factors underlying overweight and obesity. Weight gain has been described since the discovery and the use of the firstpsychotropic drugs, but seems to intensify with especially some of the second generation antipsychotic medications ; understanding of the side effects of psychotropic drugs, including their metabolic consequences (weight gain, diabetes, dyslipidemia) is essential for the psychiatrics to avoid on the one hand a risk of lack of compliance, a discontinuation of the pharmacological medication and also a risk of relapse and rehospitalization, and on the other hand to avoid acute life threatening events (diabetic ketoacidocetosis and non ketotic hyperosmolar coma, long term risk complications of diabetes and overweight).
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PMID:[Psychotropic drugs induced weight gain: a review of the literature concerning epidemiological data, mechanisms and management]. 1638 18

The serotonin (5-hydroxytryptamine) 5-HT2 receptor subfamily consists of three members, 5-HT2A, 5-HT2B, and 5-HT2C. These receptors share high homology in their amino acid sequence, have similar signaling pathways, and have been indicated to play important roles in feeding, anxiety, aggression, sexual behavior, mood, and pain. Subtype-selective agonists and antagonists have been explored as drugs for hypertension, Parkinson's disease, sleep disorders, anxiety, depression, schizophrenia, and obesity. In this study, we report the development of homogeneous agonist binding assays in a scintillation proximity assay (SPA) format to determine the high-affinity binding state of agonist compounds for the human 5-HT2C, 5-HT2A, and 5-HT2B receptors. The 5-HT2 agonist 1-(4- [125I]iodo-2,5-dimethoxyphenyl)-2-aminopropane ([125I]DOI) was used to label the high-affinity sites for the 5-HT2A and 5-HT2C receptors. The high-affinity sites for the 5-HT2B receptor were labeled with [3H]lysergic acid diethylamide. Total receptor expression was determined with the 5-HT2 antagonist [3H]mesulergine for the 5-HT2B and 5-HT2C receptors, and [3H]ketanserin for the 5-HT2A receptor. The agonist high-affinity binding sites accounted for 2.3% (5-HT(2C) receptor), 4.0% (5-HT2A receptor), and 22% (5-HT2B receptor) of the total receptor population. Competition binding studies using known agonists indicated high Z' values of the agonist binding assays in SPA format (Z' > 0.70). The Ki values of 5-HT, (R)(-)DOI, and VER-3323 for the 5-HT2A, 5-HT2B, and 5-HT2C receptors by SPA format were equivalent to published data determined by filtration binding assays. These results indicate that agonist binding assays in SPA format can be easily adapted to a high throughput assay to screen for selective 5-HT2C receptor agonists, as well as for selectivity profiling of the compounds.
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PMID:Development of homogeneous high-affinity agonist binding assays for 5-HT2 receptor subtypes. 1643 60

To establish the impact of antipsychotic medication on the incidence of diabetes, we have analysed data from the prospective French Cohort study of mortality in schizophrenia. This generated a large database of 3470 patients with schizophrenia initially enrolled in 1993 for which data collection on comorbidity has been collected systematically every three years since. The primary objective of the study was to evaluate the mortality rate in the study cohort. From this database, the prevalence and incidence of diabetes can be studied. In 1993, nine patients in 10 were prescribed conventional antipsychotics and the remainder amisulpride and clozapine. Since the introduction of risperidone and olanzapine, atypical antipsychotics are now used in one-third of patients. Multiple antipsychotic medications are used in many patients, with the exception of those receiving clozapine. At inclusion, 2.2% of patients in the study cohort had a diagnosis of diabetes. Morbidity rates were higher in females than in males (3.4% and 1.6%, respectively) and it was only in females that the standard morbidity ratio with respect to the general population was significantly elevated (2.2; 95% confidence intervals: 1.6 and 2.9). The prevalence of diabetes in the study cohort rose over the course of the study. Multivariate regression analysis was performed in order to identify potential determinants of diabetes. For pre-existing diabetes, four factors were identified: age at first hospitalisation, age, obesity and duration of schizophrenia. The same factors with the exception of length of illness were identified for the incident cases. There was no evidence for an interaction between the class and type of antipsychotic medication and risk of treatment emergent diabetes. However, the use of multiple antipsychotic treatments makes the individualisation of specific risks associated with any other antipsychotic drug impossible.
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PMID:Data on diabetes from the French cohort study in schizophrenia. 1645 48

We examined indices of the health of persons with serious mental illness. A sample of 100 adults with schizophrenia and 100 with major mood disorder were recruited from randomly selected outpatients who were receiving community-based psychiatric treatment. Participants were surveyed about health indicators using items from the National Health and Nutrition Examination Study III and the National Health Interview Survey. Their responses were compared with those of matched samples from the general population surveys. A total of 1% of persons with serious mental illness, compared with 10% from the general population sample, met criteria for all 5 of selected health indicators: nonsmoker, exercise that meets recommended standards, good dentition, absence of obesity, and absence of serious medical co-occurring illness. Within the mentally ill group, educational level, but not a diagnosis of schizophrenia versus mood disorder, was independently associated with a composite measure of health behaviors. We conclude that an examination of multiple health indicators may be used to measure overall health status in persons with serious mental illness.
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PMID:Health status of individuals with serious mental illness. 1646 43

Obesity and diabetes have caused problems for individuals with schizophrenia long before atypical antipsychotic agents. The prevalence of obesity, insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, dyslipidemia, and the Metabolic Syndrome has increased in people with schizophrenia as compared to the general population. Risk reduction studies for persons with obesity, diabetes, and cardiovascular disease indicate that cognitive/behavioral interventions that promote motivation and provide strategies to overcome the barriers in adherence to diet and activity modification are effective interventions for weight management and risk reduction. In the landmark multi-center randomized-controlled trial study, the Diabetes Prevention Project (DPP), a cognitive/behavioral intervention, was more successful in producing weight loss and preventing diabetes than the drugs metformin, troglitazone or placebo. This pilot study examined the effectiveness of a cognitive/behavioral group intervention, modified after the DPP program, in individuals with schizophrenia or schizoaffective disorder taking atypical antipsychotics in a large urban public mental health system. Outcome measures included body weight, body mass index, waist-hip ratios, and fasting glucose levels. Both groups demonstrated elevated fasting glucose levels and were obese with a mean BMI of 33. The group that received the cognitive/behavioral group intervention lost more weight than the treatment as usual group. The CB group participants lost an average of 5.4 lb or 2.9% of body weight, and those in the control group lost 1.3 lb or 0.6% body weight. The range of weight loss for the treatment group was from 1 to 20 lb. This pilot study has demonstrated that weight loss is possible with cognitive/behavioral interventions in a population with a psychotic disorder.
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PMID:A cognitive/behavioral group intervention for weight loss in patients treated with atypical antipsychotics. 1650 43


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