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)

Olanzapine, a serotonin-dopamine-receptor antagonist, is an atypical antipsychotic agent used to treat schizophrenia and other psychotic disorders. It is preferred over older antipsychotics because of its relatively low frequency of sedation, orthostatic hypotension, extrapyramidal symptoms, and anticholinergic side effects. A 45-year-old man with well-controlled type 2 diabetes mellitus experienced an abrupt worsening of his diabetes after 3 years of olanzapine therapy His hemoglobin A1c (HbA1c) level rose from a baseline of 5.9-6.2% to 12.5%. Discontinuation of olanzapine by means of a 3-month taper resulted in a reduction in HbA1c to pretreatment levels. Although cases of olanzapine-induced hyperglycemia have been documented in the literature, this complication has not been reported in a patient maintained on therapy for this duration. Clinicians should be aware of this possible complication in patients receiving long-term olanzapine therapy.
 ...
PMID:Dramatic worsening of type 2 diabetes mellitus due to olanzapine after 3 years of therapy. 1171 19

Olanzapine has been associated with insulin resistance and new-onset diabetes mellitus. A 27-year-old African-American man developed new-onset severe hyperglycemia-glucose 1240 mg/dl, with ketonuria and acidosis, but no weight gain-2 years after starting olanzapine. Although his diabetes was stabilized with insulin, his family had difficulty monitoring his therapy, and insulin was discontinued. Subsequent monotherapy with pioglitazone stabilized the patient's glucose levels, allowing him to continue taking olanzapine. Health care professionals should be aware of links between olanzapine and diabetes mellitus and of the potential for delayed recognition of complications associated with diabetes in patients who are psychotic. Insulin poses additional problems because families of patients with schizophrenia have to deal with compliance and risk of accidental or suicidal overdose. This case and others described in the literature illustrate such dilemmas and highlight the need to further study links connecting diabetes, insulin resistance, and olanzapine. Further research to determine proportionality and risk differences among various atypical antipsychotics also is warranted.
 ...
PMID:Olanzapine-associated severe hyperglycemia, ketonuria, and acidosis: case report and review of literature. 1171 20

Unlike disorders of other fields of medicine (eg., diabetes, heart disease), schizophrenia has been only marginally impacted by the study of animal models. This gap reflects the incomplete understanding of the causes and mechanisms of schizophrenia and the resulting lack of defined targets for model development. However, prior attempts at modeling in animals the complex symptoms of schizophrenia have given way to more promising component models. This review will address the evolving field of animal models of schizophrenia with a focus on models of errors in neurotransmission, and of psychophysiological deficits, with a concluding discussion of the present and future promise of genetic-based models. Evolving models based on the long-held conceptualization of schizophrenia as being based on errors in neurotransmission are discussed as regards the integration of newer findings implicating alterations in dopamine, glutamate and neurotensin function in the pathophysiology and pharmacotherapy of schizophrenia. The case for the more recent conceptualization of schizophrenia as a core deficit in information processing and stimulus filtering is discussed. Animal behavioral paradigms that model psychophysiologic constructs of stimulus processing deficits related to schizophrenia include prepulse inhibition (PPI), a model of sensorimotor gating, or latent inhibition (LI), a model of salience learning. These models represent both better supported associations with schizophrenia and more productive targets and are providing important new information regarding the psychopharmacology of schizophrenia. Genetic models of schizophrenia are based on the demonstrated heritability of the disorder and more recent pharmacogenetic findings for antipsychotic medications. Genetic-based animal models use behavioral or molecular genetic techniques to manipulate behaviors related to schizophrenia by altering the frequencies of related genes. The future development of increasingly informative animal models of schizophrenia will be dependent on a more complete understanding of schizophrenia, an integration of findings across animal models and refinements in the criteria used to assess model "validity" that better reflect the changing nature and roles of animal models of schizophrenia.
 ...
PMID:The changing roles and targets for animal models of schizophrenia. 1174 40

Olanzapine is an 'atypical' antipsychotic indicated for the treatment of schizophrenia. We analysed adverse events (AEs) reported in primary practice in England. Dispensed prescriptions issued between December 1996 and May 1998 provided exposure data. Questionnaires sent to general practitioners provided outcomes. Frequently reported AEs were: drowsiness/sedation (n = 19), extrapyramidal disorder (n = 13) and unspecified side-effects (n = 33). Events with highest incidence density in first month and reason for stopping were: drowsiness/sedation [n = 153, incidence density (ID)1 18.9], weight gain (n = 117, ID1 8.9) and malaise/lassitude (n = 65, ID1 5.2). Extrapyramidal disorders were more common in elderly population (> 70 years, ID1 3.6, risk 26.0 per 1,000 patients) compared to < 70 years (ID1 1.1, risk 8.4 per 1,000 patients). Serious suspected adverse reactions were neuroleptic malignant syndrome (n = 1) and angioneurotic ooedema (n = 2). There were eight reports of diabetes mellitus assessed as possibly due to olanzapine. Diabetes mellitus was an unlabelled AE and possible signal generated by prescription-event monitoring.
 ...
PMID:The pharmacovigilance of olanzapine: results of a post-marketing surveillance study on 8858 patients in England. 1176 20

The variation observed in individual differences for normal and psychopathological behaviors has genetic factors as a major contributor at the most distal end of a complex gene-to-behavior pathway. Research into the etiologies of such major mental diseases as schizophrenia is facilitated by adopting the approach used for complex adaptive systems as pursued by those who study coronary artery disease and diabetes. Putative risk factors for developing the liabilities to the major disorders can be inferred from population genetic strategies using twins, families, and adoptees. Weights to indicate the relative importance of such risk factors require a perspective from the use of effect sizes and odds ratios so as to make the most efficient use of scarce resources. The challenge to the field of psychology is to join in with cross-disciplinary ventures and to adapt to rapid changes with innovations in research strategies.
 ...
PMID:Psychopathology through a life span-genetic prism. 1178 54

Type 2 diabetes mellitus and impaired glucose tolerance are associated with antipsychotic treatment. Risk factors for type 2 diabetes and impaired glucose tolerance include abdominal adiposity, age, ethnic status, and certain neuropsychiatric conditions. While impaired glucose metabolism was first described in psychotic patients prior to the introduction of antipsychotic medications, treatment with antipsychotic medications is associated with impaired glucose metabolism, exacerbation of existing type 1 and 2 diabetes, new-onset type 2 diabetes mellitus, and diabetic ketoacidosis, a severe and potentially fatal metabolic complication. The strength of the association between antipsychotics and diabetes varies across individual medications, with the largest number of reports for chlorpromazine, clozapine, and olanzapine. Recent controlled studies suggest that antipsychotics can impair glucose regulation by decreasing insulin action, although effects on insulin secretion are not ruled out. Antipsychotic medications induce weight gain, and the potential for weight gain varies across individual agents with larger effects observed again for agents like chlorpromazine, clozapine, and olanzapine. Increased abdominal adiposity may explain some treatment-related changes in glucose metabolism. However, case reports and recent controlled studies suggest that clozapine and olanzapine treatment may also be associated with adverse effects on glucose metabolism independent of adiposity. Dyslipidemia is a feature of type 2 diabetes, and antipsychotics such as clozapine and olanzapine have also been associated with hypertriglyceridemia, with agents such as haloperidol, risperidone, and ziprasidone associated with reductions in plasma triglycerides. Diabetes mellitus is associated with increased morbidity and mortality due to both acute (e.g., diabetic ketoacidosis) and long-term (e.g., cardiovascular disease) complications. A progressive relationship between plasma glucose levels and cardiovascular risk (e.g., myocardial infarction, stroke) begins at glucose levels that are well below diabetic or "impaired" thresholds. Increased adiposity and dyslipidemia are additional, independent risk factors for cardiovascular morbidity and mortality. Patients with schizophrenia suffer increased mortality due to cardiovascular disease, with presumed contributions from a number of modifiable risk factors (e.g., smoking, sedentary lifestyle, poor diet, obesity, hyperglycemia, and dyslipidemia). Patients taking antipsychotic medications should undergo regular monitoring of weight and plasma glucose and lipid levels, so that clinicians can individualize treatment decisions and reduce iatrogenic contributions to morbidity and mortality.
 ...
PMID:Hyperglycemia and antipsychotic medications. 1180 85

The lengthy list of the side effects and morbidity associated with the atypical antipsychotics might make a patient with psychosis and his or her caregivers so concerned about the use of any of these medications, particularly those associated with a higher risk of diabetes, weight gain, or increased lipid levels, that they would prefer to avoid all of them. However, schizophrenia is associated with a relatively high risk for several diseases, including diabetes, that is independent of the risks that are linked to atypical antipsychotic use. Therefore, the clinician who might think, "Why use atypicals if using the typical drugs will escape the problems of monitoring and all the associated effects of diabetes and hyperglycemia?" needs to know that these problems cannot be avoided simply by choosing typical antipsychotics. Clinicians, patients, and concerned family members must balance the significant benefits of atypical antipsychotic treatment-improved cognition, reduced suicidality, and less depression-against the risks of metabolic disturbances and select a course of treatment that includes a realistic monitoring program.
 ...
PMID:Putting metabolic side effects into perspective: risks versus benefits of atypical antipsychotics. 1180 88

Atypical antipsychotics offer significant improvements over older, conventional antipsychotic agents. However, recently the newer agents have been linked to medical morbidity including hyperglycaemia, diabetes mellitus, bodyweight gain and abnormal lipid levels. Even more concerning, because of a significant risk of death, there have been numerous case reports of patients treated with clozapine or olanzapine developing diabetic ketoacidosis shortly after initiation of the drug. Much of the information concerning the medical morbidity of diabetes mellitus is based on case reports, retrospective chart reviews, naturalistic studies and cross-sectional studies. While definitive studies have yet to be reported, mounting evidence suggests that the atypical antipsychotic agents, particularly clozapine and olanzapine, may significantly impair glucose metabolism and increase the risk of diabetes in patients with schizophrenia. Diabetic ketoacidosis, although it appears to be uncommon, is of great concern secondary to the risk of death. Patients treated with atypical antipsychotic agents should be routinely screened for diabetes and other metabolic abnormalities including raised lipid levels. Patients with risk factors for diabetes should be monitored more closely. Reports and clinical experience suggest that in a case of atypical antipsychotic-associated diabetes or diabetic ketoacidosis, discontinuation of the antipsychotic agent may result in complete resolution of the hyperglycaemia and diabetes.
 ...
PMID:Atypical antipsychotic-induced diabetes mellitus: how strong is the evidence? 1182 99

Since the introduction of chlorpromazine in the 1950s, antipsychotics have been used for the treatment of schizophrenia. The phenothiazines were followed by the butyrophenones, particularly haloperidol. With all the movement disorder side effects of these medications (extrapyramidal syndrome, akathisia, tardive dyskinesia), the pharmaceutical industry has gradually released atypical antipsychotics. This class includes clozapine (released in the USA in 1990), risperidone (1994), olanzapine (1996), quetiapine (1998) and ziprasidone (2001). However, the rate of diabetes mellitus in patients with schizophrenia appeared to increase with the availability of this class of medications. In reviewing rate and degree of changes in weight, glucose control and lipid levels induced by typical and atypical antipsychotics, it was found that in contrast to case reports, there is a dearth of retrospective, open and controlled studies. However, in studies as early as 1964, significant weight increases were found to be associated with use of chlorpromazine. While the phenothiazines may have some effect on patients with chemical diabetes, there is little evidence of the typical antipsychotics producing diabetes mellitus de novo, or worsening diabetes that is already been discovered. Ziprasidone appears to be the antipsychotic with the most beneficial combination of effects: no weight gain, no change in glucose utilisation and reductions in cholesterol and serum triglycerides (TGs).
 ...
PMID:Antipsychotic medication: effects on regulation of glucose and lipids. 1182

Approximately 16 million people in the United States have diabetes, and the World Health Organization has estimated that the worldwide prevalence of diabetes will more than double from 1995 to 2025. Type 2 diabetes, the most common form of diabetes, may be 2 to 4 times more prevalent in patients with severe mental disorders. Within the psychiatric community, there is a great deal of concern about diabetes as a potential side effect of antipsychotic agents. An important population to remember in the context of treatment-emergent hyperglycemia is the 20 million people with impaired glucose tolerance (IGT) (fasting plasma glucose > 110 mg/dL and < 126 mg/dL or 2-hour postload glucose > 140 mg/dL and < 200 mg/dL according to the American Diabetes Association). This prediabetic condition has a 5% to 10% annual risk of converting to diabetes. One hypothesis for antipsychotic treatment-emergent diabetes during double-blind, randomized, controlled trials is that people who develop diabetes soon after the initiation of drug therapy for schizophrenia may have had undiagnosed IGT or diabetes before they started treatment. The emergence of diabetes in clinical practice may be due to an observation effect, but because the incidence of diabetes is greater in people with severe mental illnesses, it is crucial for psychiatrists to be aware of national guidelines for the diagnosis and treatment of type 2 diabetes.
 ...
PMID:Metabolic side effects of antipsychotics: focus on hyperglycemia and diabetes. 1191 75


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