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

Evidence on the efficacy and safety of atypical antipsychotics in children and adolescents with schizophrenia is limited. The purpose of this review is to assess the published data on the use of atypical antipsychotics in children and adolescents with schizophrenia alone and with comorbid disorders, and to establish benefit-risk guidelines for clinicians.Risperidone, olanzapine and clozapine were found to be effective in the treatment of aggression and mania. Risperidone, and possibly also olanzapine, may be the drugs of choice in children with comorbid tic disorders. Ziprasidone has some monoamine reuptake inhibition properties and may be administered as an augmenting agent in children and adolescents with schizophrenia and comorbid anxiety and mood disorders. Compared with the typical antipsychotics, the atypical drugs seem to be more effective, better tolerated and lead to better patient adherence. Importantly, the atypical antipsychotics have a lower propensity to induce extrapyramidal symptoms and a potential (shown so far only in adults) to improve cognitive function and inhibit suicidal behaviour (especially clozapine). Yet, the adverse effects associated with these agents, especially weight gain, which may also have long-term effects, can lead to non-compliance in the young population. In children and adolescents receiving clozapine, olanzapine and quetiapine (but not ziprasidone, which does not have a pro-appetite effect), particularly those with obesity or a family history of diabetes mellitus, fasting blood glucose and lipid levels must be monitored frequently. Weight gain might be better controlled when the children and their parents are properly informed about this adverse effect and diet is regulated. Another major disadvantage of the atypical antipsychotics, especially risperidone, is their association with hyperprolactinaemia, which can lead to hypogonadism-induced osteoporosis, galactorrhoea, gynaecomastia, irregular menstruation and sexual dysfunction, all seen also with typical antipsychotics. Other atypical antipsychotics, namely olanzapine and ziprasidone, have been reported to be prolactin sparing in adults, but may not be completely devoid of hyperprolactinaemic effects in children and adolescents. Thus, prolactin levels should be assessed routinely in young patients treated with atypical antipsychotics. Further, children and adolescents with hyperprolactinaemia-related effects should be switched to a prolactin-sparing agent, such as quetiapine. All atypical antipsychotics may induce sedation and they are not devoid of extrapyramidal symptoms (especially risperidone). The use of typical antipsychotics has been limited to patients who are resistant to atypical antipsychotics, intolerant to their adverse effects, or require injections or depot preparations. Further double-blind, placebo-controlled trials and long-term safety assessments are needed before definitive conclusions can be reached about the place of atypical antipsychotics in the therapeutic armamentarium of childhood-onset schizophrenia.
 ...
PMID:Benefit-risk assessment of atypical antipsychotics in the treatment of schizophrenia and comorbid disorders in children and adolescents. 1555 47

The hypothesis that there is a developmental component to subsequent adult disease initially arose from epidemiological findings relating birth size to either indices of disease risk or actual disease prevalence in later life. While components of the epidemiological analyses have been challenged, there is strong evidence that developmental factors contribute to the later risk of metabolic disease--including insulin resistance, obesity, and heart disease--as well as have a broader impact on osteoporosis, depression and schizophrenia. We suggest that disease risk is greater when there is a mismatch between the early developmental environment (i.e., the phase of developmental plasticity) versus that experienced in mature life (i.e., adulthood), and that nutritional influences are particularly important. It is also critical to distinguish between those factors acting during the developmental phase that disrupt development from those influences that are less extreme and act through regulated processes of epigenetic change. A model of the relationship between the developmental and mature environment is proposed and suggests interventional strategies that will vary in different population settings.
 ...
PMID:Life-long echoes--a critical analysis of the developmental origins of adult disease model. 1556 79

Psychiatry is constantly faced with challenges related to the medical status of its patients and comorbid effects of pharmacologic treatment for psychiatric disorders. Other articles in this supplement review how obesity, diabetes, and dyslipidemia play a role in the treatment of schizophrenia, but these issues are by no means limited to schizophrenia. As the population of the United States becomes more obese and sedentary over time, risk factors for cardiovascular disease and diabetes are increasing in prevalence and affect the treatment of any psychiatric condition. As our understanding of how metabolic factors contribute to disease grows, it has become clear that a clustering of individual dysmetabolic factors, now known as metabolic syndrome, can contribute to significant morbidity and mortality and should be accounted for in the treatment of psychiatric conditions.
 ...
PMID:Metabolic syndrome: epidemiology and consequences. 1560 Mar 80

Obesity is an epidemic in this country and much of the rest of the developed world. It is a major contributor to a range of metabolic disorders responsible for much of the medical morbidity and mortality that burden our society. The combination of the costs to society of the chronic illness of schizophrenia with the costs of obesity and the chronic illnesses associated with it, e.g., metabolic disorders, diabetes, dyslipidemias, and cardiovascular disease, represents a major public health problem. Obesity in schizophrenia is accentuated even further largely through illness-related factors, like poor dietary conditions and more sedentary lifestyles, and particularly because many of the psychiatric medications (antipsychotics, mood stabilizers, and antidepressants) used to combat this devastating illness themselves result in weight gain that, if untreated, may result in the usual obesity-associated morbidity and mortality. This article is intended to review some of the physiology of obesity and obesity-related metabolic disorders, the risks to schizophrenia patients engendered by obesity, the evidence for weight gain associated with the antipsychotic drugs, and the possible mechanisms involved in antipsychotic medication-associated weight gain.
 ...
PMID:Schizophrenia and obesity: impact of antipsychotic medications. 1560 Mar 81

Dyslipidemia is an increasing problem in most industrialized societies and is a risk factor for coronary heart disease (CHD). Imbalances in individual lipid components, including total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and serum triglycerides, have each been shown to contribute to this increased risk. Certain psychiatric patient populations, such as those afflicted with schizophrenia, are of particular concern. Psychiatric patients with schizophrenia are naturally at increased risk for dyslipidemia and obesity, in part due to poor diet and sedentary lifestyle, but these conditions can be exacerbated by some antipsychotic medications. Clozapine and olanzapine, for example, appear to be associated with hyperlipidemia, which may be associated with changes in body weight. Other, newer antipsychotic agents may exhibit less liability for weight gain and the development of dyslipidemia. This review is intended to briefly highlight the association between dyslipidemia and cardiovascular disease, the changes in serum lipids associated with some antipsychotic agents, and how these changes in serum lipids affect the monitoring of schizophrenia patients.
 ...
PMID:Dyslipidemia and atypical antipsychotic drugs. 1560 Mar 82

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.
 ...
PMID:Abnormalities of glucose metabolism associated with atypical antipsychotic drugs. 1560 Mar 83

Weight gain has been documented as a significant adverse effect associated with many of the atypical antipsychotic medications. Several recent reports have linked a -759C/T polymorphism of the 5HT2C receptor gene and obesity as well as chlorpromazine, risperidone, and clozapine induced to weight gain. This aim was to determine the association between changes in body mass index (BMI) during clozapine treatment and the -759C/T polymorphism of the 5HT2C receptor gene. This study included 41 patients with treatment-refractory schizophrenia (DSM-IV) who were followed prospectively during treatment with clozapine. Weight and height measurements were obtained prior to starting clozapine and after 6-months of treatment. Genomic DNA was isolated from a whole blood sample and analyzed for the -759C/T polymorphism of the 5HT2C receptor gene. A chi(2) analysis comparing whether or not the subjects carried a -759T allele in subjects grouped as having an increase of more or less than 7% of their baseline BMI during treatment with clozapine found that the presence of the -759T allele was significantly higher in subjects with less than or equal to a 7% increase in baseline BMI compared to those with a greater than 7% increase in BMI. A multiple linear regression analysis showed that both baseline BMI and the presence or absence of the -759T allele had significant effects on 6-month BMI. The T allele may have a protective function in preventing significant weight gain from clozapine. Subjects without the -759T variant allele were at a greater risk for weight gain from clozapine over 6-months compared to those with the -759T allele.
 ...
PMID:Clozapine-induced weight gain associated with the 5HT2C receptor -759C/T polymorphism. 1563 67

Since the cloning of the histamine H(3) receptor cDNA in 1999 by Lovenberg and co-workers, this histamine receptor has gained the interest of many pharmaceutical companies as a potential drug target for the treatment of various important disorders, including obesity, attention-deficit hyperactivity disorder, Alzheimer's disease, schizophrenia, as well as for myocardial ischaemia, migraine and inflammatory diseases. Here, we discuss relevant information on this target protein and describe the development of various H(3) receptor agonists and antagonists, and their effects in preclinical animal models.
 ...
PMID:The histamine H3 receptor: from gene cloning to H3 receptor drugs. 1566 57

Benzazepines 1 and 2 (SCH 23390 and SCH 39166, respectively) are two classical benzazepine D1/D5 antagonists, with Ki values 1.4 and 1.2 nM, respectively. Compound 2 has been in human clinical trials for a variety of diseases, including schizophrenia, cocaine addition, and obesity. Both 1 and 2 displayed low plasma levels and poor oral bioavailability, due to rapid first-pass metabolism of the phenol moieties. Several heterocyclic systems containing an N-H hydrogen bond donor were synthesized and evaluated as phenol isosteres. The preference orientation of the hydrogen bond was established by comparison of analogues containing different NH vectors. Replacement of the phenol group of 2 with an indole ring generated the first potent D1/D5 antagonist 11b. Further optimization led to the synthesis of very potent benzimidazolones 19, 20 and benzothiazolone analogues 28, 29. These compounds have excellent selectivity over D2-D4 receptors, alpha2a receptor, and the 5-HT transporter. Compared to 2, these heterocyclic phenol isosteres showed much better pharmacokinetic profiles as demonstrated by rat plasma levels. In sharp contrast, similar phenolic replacements in 1 decreased the binding affinity dramatically, presumably due to a conformational change of the pendant phenyl group. However, one indazole compound 33 was identified as a potent D1/D5 ligand in this series.
 ...
PMID:Dopamine D1/D5 receptor antagonists with improved pharmacokinetics: design, synthesis, and biological evaluation of phenol bioisosteric analogues of benzazepine D1/D5 antagonists. 1568 53

A higher prevalence of diabetes mellitus (DM) has been reported in schizophrenic patients for decades. But the risk factors for diabetes in these patients were not well understood. The aim of our study is to establish the prevalence of DM in patients with schizophrenia in Taiwan and discover the risk factors associated with it. In 246 recruited schizophrenic patients, the prevalence of DM was 9.8%, not significantly different from that of the general population in Taiwan. However, we found a significantly higher prevalence of DM in younger schizophrenic patients (p=0.001) than in the general population, but not in older patients (p>0.10). Our results showed old age, a longer duration of illness, obesity, and having a family history of DM were independent factors associated with DM in schizophrenia. These results suggest that schizophrenia may make young people more vulnerable to developing DM. Further large-scale, controlled studies should be done to confirm our results.
 ...
PMID:Diabetes mellitus in patients with schizophrenia in Taiwan. 1586 53


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