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

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).
 ...
PMID:[Psychotropic drugs induced weight gain: a review of the literature concerning epidemiological data, mechanisms and management]. 1638 18

Clozapine is an atypical antipsychotic drug with unique pharmacological and therapeutic properties. Unlike the typical antipsychotic drug, haloperidol, clozapine does not cause extrapyramidal side effects; however, weight gain, dyslipidemia, and type II diabetes are commonly associated with the use of this drug in subjects with schizophrenia. The aim of this study was to profile gene expression in the rat striatum following clozapine treatment. Chronic treatment with clozapine revealed upregulation of several genes including the glucose-dependent insulinotropic polypeptide (GIP) gene by over 200% in the rat striatum. The cDNA array results for the GIP gene were confirmed by real-time RT-PCR as well as by radioimmunoassay. Expression of the GIP gene in the central nervous system is consistent with the results of retinal GIP gene expression as reported by other investigators. Taken together, these findings implicate the possible role of GIP as a neuromodulator in the central nervous system. GIP is an insulinotropic agent with stimulatory effects on insulin synthesis and release from the pancreas. However, changes in brain GIP levels are most likely unrelated to the metabolic adverse effects (dyslipidemia, type II diabetes, weight gain) associated with clozapine treatment. Therefore, we also measured GIP gene expression in the K-cell-rich regions, duodenum and jejunum (small intestine), and plasma GIP levels using radioimmunoassay following chronic treatment with clozapine. GIP mRNA levels in the small intestine and the plasma GIP at the protein level were significantly elevated in clozapine-treated subjects. Furthermore, as observed in humans, chronic clozapine treatment also caused weight gain, and increased levels of insulin, triglycerides and leptin in the plasma. These results suggest that adverse metabolic effects associated with clozapine treatment may be related to its ability to increase intestinal gene expression for GIP.
 ...
PMID:cDNA array reveals increased expression of glucose-dependent insulinotropic polypeptide following chronic clozapine treatment: role in atypical antipsychotic drug-induced adverse metabolic effects. 1640 76

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.
 ...
PMID:A cognitive/behavioral group intervention for weight loss in patients treated with atypical antipsychotics. 1650 43

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.
 ...
PMID:A case series: evaluation of the metabolic safety of aripiprazole. 1694 Mar 38

Patients with schizophrenia and bipolar disorder are vulnerable to developing key modifiable risk factors for cardiovascular disease, such as obesity, smoking, hypertension, dyslipidemia, and type 2 diabetes mellitus. In addition, mood stabilizers, anticonvulsants, and antipsychotic medications, which are commonly used to treat schizophrenia and bipolar disorder, have been linked to risk for adverse metabolic changes in patients. This article reviews the current literature on the prevalence of medical risk factors in the general population as well as in those patients with schizophrenia or bipolar disorder and discusses treatment strategies and lifestyle changes that patients can make in order to reduce their risks for certain diseases.
 ...
PMID:Medical risk in patients with bipolar disorder and schizophrenia. 1696 86

It is well known, that patients with schizophrenia exhibit increased rates of cardiac morbidity and mortality. Frequent cardiovascular diseases are only partially explained by lifestyle, inactivity, dietary habits and nicotine abuse, but also by reduced compliance in prevention programs. On the other hand, it has been shown that particularly atypical antipsychotic agents are differentially responsible for high rates of obesity, hypertriglyceridemia, and diabetes. Therefore, a standardized evaluation of corresponding parameters is indicated in every patient. If needed, modulation of the medication regimen has to be performed. Additionally, a dietary counselling of the patient and his family should be offered. Besides pharmacological approaches to normalize dyslipidemia, specific behavioural therapy programmes are an option that may alter metabolic parameters. Threatening cardiac complications in long-term treatment of schizophrenia may also be the result of direct side effects under treatment with antipsychotics, like QT-prolongation triggering major arrhythmias. For prevention, predisposing risk factors like electrolyte disturbances, pre-existing cardiac diseases, co-medication with QT prolonging drugs and medication with potential cytochrome P450 interaction have to be taken into consideration.
 ...
PMID:[Cardiac complications in patients with schizophrenic disorders]. 1697 9

Patients with schizophrenia and bipolar disorder are vulnerable to developing key modifiable risk factors for cardiovascular disease, such as obesity, smoking, hypertension, dyslipidemia, and type 2 diabetes mellitus. In addition, mood stabilizers, anticonvulsants, and antipsychotic medications, which are commonly used to treat schizophrenia and bipolar disorder, have been linked to risk for adverse metabolic changes in patients. This review reports the prevalence of medical risk factors in the general population as well as in those patients with schizophrenia or bipolar disorder and discusses treatment strategies and lifestyle changes that patients can make in order to reduce their risks for certain diseases.
 ...
PMID:Medical risk in patients with bipolar disorder and schizophrenia. 1720 Oct 46

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.
 ...
PMID:Metabolic considerations in the use of antipsychotic medications: a review of recent evidence. 1728 24

Cardiovascular disease (CVD), which includes coronary heart, cerebrovascular, and peripheral vascular disease, is the leading cause of death in the United States and most developed countries, accounting for about 50% of all deaths. The major risk factors include obesity and its consequences, dyslipidemia, hypertension, insulin resistance leading to diabetes, and cigarette smoking. In developing countries, CVD will become the leading cause of death due to alarming increases in obesity, sedentary lifestyles, cigarette smoking, and improvements in prevention and treatment of malnutrition and infection. Compared with nonschizophrenics, patients with schizophrenia have a 20% shorter life expectancy (i.e., from 76 to 61 years). In general populations, about 1% die from suicide compared with about 10% among patients with schizophrenia (relative risk = 10). For CVD, the corresponding figures are 50% and about 75% (relative risk = 1.5). In patients with schizophrenia, however, CVD occurs more frequently and accounts for more premature deaths than suicide. Patients with schizophrenia have alarmingly higher rates of obesity, dyslipidemia, hypertension, diabetes, and cigarette smoking than nonschizophrenic individuals in the general population. Compounding these data, patients with schizophrenia have less access to medical care, consume less medical care, and are less compliant. Primary prevention strategies should include the choice of antipsychotic drug regimens that do not adversely affect the major risk factors for CVD.
 ...
PMID:Increasing global burden of cardiovascular disease in general populations and patients with schizophrenia. 1753 93

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.
 ...
PMID:Antipsychotic medications: metabolic and cardiovascular risk. 1753 94


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>