olanzapine and Diabetes-Mellitus--Type-2

Schizophrenia, a serious psychiatric disorder, is among the top 10 global causes of disability and affects nearly 1% of the world population. Antipsychotics constitute the best treatment for patients with schizophrenia, however, this treatment class carries a high risk of metabolic syndrome, including lipid abnormalities. Indeed, the risk of metabolic syndrome would be increased in the population with schizophrenia compared to the general population. The objective is to summarize the prevalence, the mechanisms, and the potential treatments of antipsychotic-induced metabolic syndrome. This is a narrative review of the literature. We searched the electronic database Medline, accessed through PubMed, to find studies that investigated the prevalence and treatments of metabolic syndrome in the adult population using antipsychotics. The prevalence of metabolic syndrome in patients treated with antipsychotics ranges from 37% to 63%. Antipsychotic iatrogenic effects include weight gain/increased waist circumference, dyslipidemia, insulin resistance/type 2 diabetes, and hypertension. Clozapine and olanzapine are reported to precipitate the onset of metabolic syndrome features. In patients with metabolic syndrome, an antipsychotic with less metabolic side effects such as lurasidone, lumateperone, ziprasidone, and aripiprazole should be prioritized. Unlike medications, aerobic exercise and dietetic counseling were found to be efficient as the nonpharmacologic treatment of antipsychotic-induced metabolic syndrome. Few pharmacological treatments were proven effective against weight gain in this patient population. The risk of metabolic syndrome induced by antipsychotics should be early recognized and closely monitored. Primary and secondary prevention of metabolic syndrome or onset of its feature might help reduce the risk of death for patients using antipsychotics.

Topics: Adult; Antipsychotic Agents; Clozapine; Diabetes Mellitus, Type 2; Dyslipidemias; Humans; Hypertension; Metabolic Syndrome; Olanzapine; Schizophrenia; Weight Gain

Antipsychotics are used increasingly in youth for nonpsychotic and off-label indications, but cardiometabolic adverse effects and (especially) type 2 diabetes mellitus (T2DM) risk have raised additional concern.. To assess T2DM risk associated with antipsychotic treatment in youth.. Systematic literature search of PubMed and PsycINFO without language restrictions from database inception until May 4, 2015. Data analyses were performed in July 2015, and additional analyses were added in November 2015.. Longitudinal studies reporting on T2DM incidence in youth 2 to 24 years old exposed to antipsychotics for at least 3 months.. Two independent investigators extracted study-level data for a random-effects meta-analysis and meta-regression of T2DM risk.. The coprimary outcomes were study-defined T2DM, expressed as cumulative T2DM risk or as T2DM incidence rate per patient-years. Secondary outcomes included the comparison of the coprimary outcomes in antipsychotic-treated youth with psychiatric controls not receiving antipsychotics or with healthy controls.. Thirteen studies were included in the meta-analysis, including 185,105 youth exposed to antipsychotics and 310,438 patient-years. The mean (SD) age of patients was 14.1 (2.1) years, and 59.5% were male. The mean (SD) follow-up was 1.7 (2.3) years. Among them, 7 studies included psychiatric controls (1,342,121 patients and 2,071,135 patient-years), and 8 studies included healthy controls (298,803 patients and 463,084 patient-years). Antipsychotic-exposed youth had a cumulative T2DM risk of 5.72 (95% CI, 3.45-9.48; P < .001) per 1000 patients. The incidence rate was 3.09 (95% CI, 2.35-3.82; P < .001) cases per 1000 patient-years. Compared with healthy controls, cumulative T2DM risk (odds ratio [OR], 2.58; 95% CI, 1.56-4.24; P < .0001) and incidence rate ratio (IRR) (IRR, 3.02; 95% CI, 1.71-5.35; P < .0001) were significantly greater in antipsychotic-exposed youth. Similarly, compared with psychiatric controls, antipsychotic-exposed youth had significantly higher cumulative T2DM risk (OR, 2.09; 95% CI, 1.50-52.90; P < .0001) and IRR (IRR, 1.79; 95% CI, 1.31-2.44; P < .0001). In multivariable meta-regression analyses of 10 studies, greater cumulative T2DM risk was associated with longer follow-up (P < .001), olanzapine prescription (P < .001), and male sex (P = .002) (r(2) = 1.00, P < .001). Greater T2DM incidence was associated with second-generation antipsychotic prescription (P ≤ .050) and less autism spectrum disorder diagnosis (P = .048) (r(2) = 0.21, P = .044).. Although T2DM seems rare in antipsychotic-exposed youth, cumulative risk and exposure-adjusted incidences and IRRs were significantly higher than in healthy controls and psychiatric controls. Olanzapine treatment and antipsychotic exposure time were the main modifiable risk factors for T2DM development in antipsychotic-exposed youth. Antipsychotics should be used judiciously and for the shortest necessary duration, and their efficacy and safety should be monitored proactively.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Child; Child, Preschool; Confounding Factors, Epidemiologic; Diabetes Mellitus, Type 2; Female; Humans; Incidence; Male; Odds Ratio; Olanzapine; Risk Factors; Young Adult

The use of antipsychotic therapy has been proven to have an association with the incidence of diabetes mellitus. The use of atypical antipsychotics is shown to have a higher association, in contrast with typical antipsychotics. Olanzapine and Clozapine appear to have the highest rates of diabetes mellitus incidence, due to their tendency to affect glucose metabolism compared with other antipsychotic drugs. In this research the main goal is to understand which antipsychotic drugs are the most diabetogenic and to show the mechanisms involved in the glucose metabolism dysregulations with special focus on Olanzapine considering it is a very commonly prescribed and used drug especially among patients with schizophrenia.. Our study is a literature based research. For our research we reviewed 41 Pubmed published articles from 2005 to 2015.. According to most of the literature, from all the antipsychotics, Clozapine followed by Olanzapine appear to be the atypical neuroleptics that most relate to metabolic syndrome and Diabetes. The basis for this metabolic dysregulations appears to be multifactorial in origin and a result of the drugs, environment and genes interaction.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Clozapine; Diabetes Mellitus, Type 2; Female; Humans; Male; Olanzapine; Risk Assessment; Schizophrenia

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Diabetes Mellitus, Type 2; Humans; Olanzapine; Receptors, Adrenergic; Receptors, Dopamine; Receptors, Serotonin; Schizophrenia; Secondary Prevention; Weight Gain

Management of bipolar disorder (BPD) may require multiple medications, including lithium, anticonvulsants, and antipsychotics (both conventional and atypical). Updated treatment guidelines reflect an expanded role for atypical antipsychotics (AAPs) in BPD treatment. Five AAPs--olanzapine, risperidone, quetiapine, ziprasidone, and aripiprazole--are approved by the US Food and Drug Administration (FDA) as monotherapy for first-line treatment of acute manic and (except for quetiapine) mixed episodes. Two AAPs--olanzapine (in fixed-dose combination with fluoxetine) and quetiapine--are also FDA approved for bipolar depression. For long-term maintenance therapy, one option is to continue effective, well-tolerated acute phase treatment; however, only olanzapine and aripiprazole are FDA approved for maintenance, based on evidence from randomized, placebo-controlled clinical trials. Although head-to-head comparisons are scarce, meta-analysis data suggest that olanzapine, risperidone, quetiapine, ziprasidone, and aripiprazole have similar antimanic efficacy; therefore, AAP selection for this indication should be guided by other considerations such as safety, tolerability, and cost. Safety and tolerability issues to consider when selecting an AAP include metabolic dysfunction (weight gain, type 2 diabetes, and dyslipidemia); hyperprolactinemia; extrapyramidal symptoms; QTc prolongation; and pharmacokinetic drug interactions.

Topics: Antipsychotic Agents; Aripiprazole; Arrhythmias, Cardiac; Benzodiazepines; Bipolar Disorder; Diabetes Mellitus, Type 2; Dibenzothiazepines; Drug Evaluation; Drug Interactions; Drug Therapy, Combination; Dyslipidemias; Humans; Hyperprolactinemia; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Thiazoles; Treatment Outcome; Weight Gain

Most of the data evaluating the potential relationship between diabetes, schizophrenia, and anti-psychotics currently derive from retrospective analysis. Relevant confounders of such data include screening and selection bias. Prospective data collected from randomized controlled trials may reduce such biases. As no single trial has glucose comparisons as a primary endpoint, we undertook a systematic review of available data.. Embase, HealthStar, MEDLINE, Pre-MEDLINE, and PsycINFO databases were searched online for relevant articles. Abstracts from major congresses held between January 2000 and April 2006 were included. Search terms included all currently available antipsychotics: olanzapine, risperidone, clozapine, quetiapine, ziprasidone, aripiprazole, haloperidol, chlorpromazine, and zotepine.. Prospective clinical trials involving schizophrenia patients with no stated previous glucose abnormalities randomly assigned to cohorts receiving active or placebo comparator antipsychotic medications were included with no restrictions on study length. 16 studies were from peer-reviewed publications, 4 were from posters at major congresses, and 2 were available only on Internet-based sites.. Glucose parameters reported included fasting and random glucose and glycosylated hemoglobin. Data reported included mean changes and categorical reports of abnormal levels.. Data were available in 6329 patients from 22 trials. The most common comparator agents were aripiprazole and olanzapine in 4 studies including 1432 patients. 14 studies reported fasting and 9 studies reported nonfasting data. 15 studies were a minimum of 5 months, with 8 studies of at least 1 year's duration. No consistent significant glucose differences were found between any comparator antipsychotics or placebo in any trial.. In contrast to some of the retrospective data, an analysis of prospective data from randomized clinical trials showed no consistent significant differences in the incidence of treatment-emergent glucose abnormalities in patients treated with antipsychotics. The reduction in both screening and selection biases may be relevant. Although one third of the studies had at least 1 year's duration, the data are not sufficient to reach conclusions regarding patients receiving longer-term treatment with atypical antipsychotics.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Blood Glucose; Clozapine; Diabetes Mellitus, Type 2; Humans; Olanzapine; Piperazines; Quinolones; Schizophrenia

Among the atypical antipsychotics, clozapine and olanzapine are known to cause significant weight gain. Along with quetiapine, they may impair glucose metabolism and increase the risk for type 2 diabetes. They are also associated with a rise in triglyceride levels and an increased risk for coronary artery disease. Clinicians should take these risks seriously in prescribing these antipsychotics and employ intelligent safeguards if and when they use them.

Topics: Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Humans; Hypertriglyceridemia; Leptin; Neurotransmitter Agents; Olanzapine; Weight Gain

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Clozapine; Diabetes Mellitus, Type 2; Humans; Middle Aged; Olanzapine; Risk Factors; Schizophrenia; Selective Serotonin Reuptake Inhibitors; Serotonin Antagonists

Five new antipsychotic drugs introduced in the United States in the last decade offer physicians the ability to treat patients with schizophrenia and bipolar mania without the adverse effects of the first-generation antipsychotics. In this article, the authors discuss the advantages and side effects of these agents and present a guide to help physicians choose the optimal drug in the most favorable formulation for each patient.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Diabetes Mellitus, Type 2; Dibenzothiazepines; Drug Administration Schedule; Humans; Hyperprolactinemia; Mental Disorders; Olanzapine; Patient Compliance; Piperazines; Practice Guidelines as Topic; Prescription Fees; Quetiapine Fumarate; Quinolones; Risk Assessment; Risperidone; Thiazoles; Torsades de Pointes; Treatment Outcome; Weight Gain

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.

Topics: Antipsychotic Agents; Benzodiazepines; Cardiovascular Diseases; Cholesterol; Cholesterol, VLDL; Clozapine; Coronary Disease; Diabetes Mellitus, Type 2; Humans; Hyperlipidemias; Obesity; Olanzapine; Risk Factors; Schizophrenia; Triglycerides; Weight Gain

After the introduction of the so-called "atypical antipsychotics" in the clinical experience hyperglycemia as well as increased triglyceride and cholesterol serum levels were reported in patients treated with some of these agents. In this article, the recently published population-based studies are reviewed.. According to the available data, the risk to develop type 2 diabetes mellitus or hyperlipidemia in patients treated with clozapine and olanzapine is increased. The underlying pathomechanism still remains widely unclear. Since overweight is a known risk factor for type 2 diabetes mellitus, the weight-inducing effect of atypical antipsychotics may play an important role.. Since metabolic disorders often lead to severe diseases, these side effects of antipsychotics should be paid more attention.

Topics: Antipsychotic Agents; Benzodiazepines; Body Weight; Clozapine; Diabetes Mellitus, Type 2; Humans; Hypercholesterolemia; Hypertriglyceridemia; Olanzapine; Pirenzepine; Risk

Topics: Adolescent; Adult; Age Factors; Aged; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Body Weight; Clinical Trials as Topic; Clozapine; Diabetes Mellitus; Diabetes Mellitus, Type 2; Dibenzothiazepines; Female; Glucose; Haloperidol; Humans; Intellectual Disability; Male; Mental Disorders; Metabolic Syndrome; Middle Aged; Olanzapine; Quetiapine Fumarate; Retrospective Studies; Risk Factors; Risperidone; Schizophrenia; Sex Factors; Time Factors; Weight Gain

Hyperglycaemia is known occasionally to occur with conventional neuroleptics, but has more recently been associated with atypical antipsychotics especially clozapine and olanzapine. This article examines more closely this association. A review of relevant published literature from 1970 to date was undertaken following Medline and Embase searches in June 2000. Hyperglycaemia with clozapine was widely reported: spontaneous reports of either hyperglycaemia or ketoacidosis were described in a total of 17 people. In a five-year naturalistic study, 30.5% of patients taking clozapine were eventually diagnosed with Type 2 diabetes. With olanzapine, a total of 10 cases of hyperglycaemia and 5 cases of ketoacidosis have been published. Reports of hyperglycaemia with other atypicals are relatively scarce. The association of hyperglycaemia or ketoacidosis with clozapine and olanzapine appears to be a true drug-induced effect. Risk factors may include male gender, age of around 40 years and being non-Caucasian. The management of hyperglycaemia depends on the causative agent. With clozapine, treatment with oral hypoglycaemics has been successful. With olanzapine, other atypical antipsychotics may be considered. Blood glucose monitoring is essential for all patients starting clozapine or olanzapine.

Topics: Adult; Age Factors; Antipsychotic Agents; Benzodiazepines; Clozapine; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Female; Humans; Hyperglycemia; Male; Olanzapine; Pirenzepine; Racial Groups; Sex Factors

Clozapine and olanzapine are some of the most effective antipsychotics, but both are associated with weight gain and relevant metabolic disturbances, including pre-diabetes and diabetes. Non-pharmacological/behavioural interventions have had limited effects counteracting these adverse effects. Semaglutide, a glucagon-like peptide 1 receptor agonist, is approved for the treatment of type 2 diabetes and obesity. We will investigate the long-term effects of add-on treatment with semaglutide once a week versus placebo once a week on the metabolic status in pre-diabetic (glycated haemoglobin A1c (HbA1c) 35-47 mmol/mol (5.4%-6.4%) and diabetic (HbA1c 48-57 mmol/mol (6.5%-7.4%)) patients diagnosed with a schizophrenia spectrum disorder who initiated clozapine or olanzapine treatment within the last 60 months.. This is a 26-week, double-blinded, randomised, placebo-controlled trial. Altogether, 104 patients diagnosed with a schizophrenia spectrum disorder, aged 18-65 years, with pre-diabetes or diabetes will be randomised to injections of 1.0 mg semaglutide once a week or placebo for 26 weeks. The primary endpoint is change from baseline in HbA1c. Secondary endpoints include changes in body weight, hip and waist circumference and plasma levels of insulin, glucagon, glucose, and C-peptide, insulin sensitivity, beta cell function, hepatic function, fibrosis-4 score, lipid profile, incretin hormones, bone markers, body composition, bone density, proteomic analyses and oxidative stress markers. Together with alcohol, tobacco and drug use, potential effects on the reward value of a sweet-fat stimulus, psychopathology, level of activity and quality of life will also be assessed.. This study is approved by the Danish Medicines Agency and the regional scientific ethics committee of the Capital Region of Denmark (committee C, #H-20019008) and will be carried out in accordance with International Council for Harmonisation Good Clinical Practice guidelines and the Helsinki Declaration. The results will be disseminated through peer-review publications and conference presentations.. NCT04892199.

Topics: Clozapine; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Olanzapine; Prediabetic State; Proteomics; Quality of Life; Randomized Controlled Trials as Topic; Schizophrenia

Antipsychotics (APs) are the cornerstone of treatment for schizophrenia (SCZ) but are unfortunately associated with serious metabolic adverse effects including weight gain and type 2 diabetes. The pathophysiology of AP-induced metabolic dysfunction is largely undetermined. Brain insulin resistance has been posited to be at the cross-roads of many cognitive and metabolic disorders, and disruption of central insulin action has emerged as a possible explanatory mechanism underlying AP induced metabolic dysfunction. Previous studies suggest that change in neuroimaging-based parameters with intranasal insulin administration can be leveraged to investigate brain insulin resistance. In this proof-of-concept study, we will utilize neural signatures of insulin action in the brain to examine if APs disrupt brain insulin signaling. It is hypothesized that: 1) intranasal insulin (INI), but not intranasal placebo (INP), will change cerebral blood flow and resting state connectivity, as well as increase glutamate levels in the striatum and dorsolateral prefrontal cortex; 2) oral olanzapine (OLA), but not oral placebo (PL), will inhibit the effect of INI on these parameters. Thirty-two healthy volunteers will undergo a single blind, cross-over design, wherein all participants receive the following four treatment combinations, 2-6 weeks apart, in a random sequence: INP + PL, INP + OLA, INI + PL, and INI + OLA. Participants will undergo an MRI-based assay of brain insulin resistance 15 minutes after administering 160 IU INI or INP. The scanning protocol includes resting and task-based functional MRI, arterial spin labelling, and proton magnetic resonance spectroscopy. Demonstrating that OLA can acutely induce brain insulin resistance is clinically relevant to metabolic health in SCZ. Evidence of brain insulin resistance induced by acute AP dosing can inform the early use of adjunctive insulin sensitizers for the treatment of metabolic comorbidities associated with AP treatment in severe mental illness. Trial registration ClinicalTrials.gov Registration: NCT03741478.

Topics: Antipsychotic Agents; Brain; Cross-Over Studies; Diabetes Mellitus, Type 2; Humans; Insulin; Insulin Resistance; Insulin, Regular, Human; Magnetic Resonance Imaging; Olanzapine; Single-Blind Method

Treatment with antipsychotics is associated with an increased risk of type 2 diabetes mellitus (T2D), and increased levels of inflammatory biomarkers are present in patients with T2D. We previously demonstrated that the glucagon-like peptide-1 receptor agonist liraglutide significantly reduced glucometabolic disturbances and body weight in prediabetic, overweight/obese schizophrenia-spectrum disorder patients treated with clozapine or olanzapine. This study aims to assess the involvement of cytokines in the therapeutic effects of liraglutide.. Serum concentrations of 10 cytokines (interferon-γ [IFN-γ], tumor necrosis factor-α, interleukin 1β [IL-1β], IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, and IL-13) from fasting prediabetic and normal glucose-tolerant (NGT) patients with schizophrenia-spectrum disorders were measured using multiplexed immunoassays. Prediabetic patients were randomized to 16 weeks of treatment with liraglutide or placebo, and cytokines were measured again at the end of the treatment.. IFN-γ (1.98 vs 1.17 pg/ml, P = .001), IL-4 (0.02 vs 0.01 pg/ml, P < .001), and IL-6 (0.73 vs 0.46 pg/ml, P < .001) were significantly higher in prediabetic (n = 77) vs NGT patients (n = 31). No significant changes in cytokine levels following treatment with liraglutide (n = 37) vs placebo (n = 40) were found.. Prediabetic vs NGT patients with schizophrenia treated with clozapine or olanzapine had increased serum levels of several proinflammatory cytokines, further substantiating the link between inflammation and T2D. Treatment with liraglutide did not affect the investigated cytokines. Further testing of these findings in larger numbers of individuals is needed.

Topics: Biomarkers; Clozapine; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Interleukin-4; Interleukin-6; Liraglutide; Olanzapine; Prediabetic State; Schizophrenia

This study was designed to investigate whether a preventive weight management program (WMP) reduces weight gain during olanzapine (OLZ) treatment. Moreover, we examined the effects of intervention on metabolic parameters.. Patients (N = 100) with schizophrenia or schizoaffective disorder (DSM-IV) who had commenced treatment with OLZ were recruited. Following a run-in period of 4 weeks, 74 patients who had gained at least 1.5 kg body weight were randomized to receive either 12 bi-weekly WMP sessions (prevention group (PG), n = 36), or usual care (control group (CG), n = 38). Anthropometric and metabolic parameters were assessed after the 24-week intervention phase and a 24-week follow-up.. Forty-two percent of 74 participants (PG: 36.1%, CG: 47.4%) finished the 24-week intervention phase while 34% of them (PG: 30.6%, CG: 36.8%) completed the 48-week study. There was no significant difference in weight gain between groups (PG: + 3.4 ± 4.2 kg vs. CG: + 4.5 ± 6.1 kg, P = 0.184) after 24 weeks. Nevertheless, PG showed a significantly smaller increase in waist circumference than CG (PG: + 4.6 ± 8.3 cm, CG: + 10.1 ± 7.3 cm, P = 0.019) after 48 weeks. Furthermore, PG showed a significantly smaller increase in fasting glucose (P = 0.031) and 2-h glucose after oral glucose load (P = 0.018) than CG.. These results suggest that preventive WMP may reduce the risk of abdominal obesity and deterioration of glucose metabolism in OLZ-treated patients.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Dyslipidemias; Early Medical Intervention; Female; Glucose Intolerance; Humans; Male; Middle Aged; Obesity; Olanzapine; Psychotic Disorders; Schizophrenia; Weight Reduction Programs

This study was undertaken to examine if patients exhibit more pronounced metabolic abnormalities after 8-year treatment with clozapine or olanzapine than before, and also to investigate whether there exist any differences between long-term clozapine and olanzapine therapies regarding metabolic side- effects.. Fifty psychiatric outpatients diagnosed with schizophrenia or schizoaffective disorder and on treatment with clozapine or olanzapine were studied during 8 years. Fasting blood or serum samples for glucose, lipids, prolactin and antipsychotic drug concentrations were analyzed. In addition, body mass index was calculated.. More patients treated with olanzapine compared with those treated with clozapine ended with their medication, in most cases because of diabetes mellitus and/or hyperlipidemia, during the 8-year follow-up. Also more patients treated with olanzapine compared with those treated with clozapine developed manifest diabetes mellitus during the 8-year period. Prolactin levels were higher in the patients treated with olanzapine compared with in those treated with clozapine at study start, but there were no differences in the other parameters between the treatment groups at study start. In the patients remaining on their medication all 8 years, the glucose level increased over time in the clozapine group, but not in the olanzapine group, whereas body mass index and lipids were unchanged over time in both treatment groups.. Our findings point to that both olanzapine and clozapine long-term treatments cause development of hyperglycemia and/or hyperlipidemia. Furthermore, olanzapine long-term treatment seems to more often lead to development of manifest diabetes mellitus than long-term treatment with clozapine.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Clozapine; Diabetes Mellitus, Type 2; Female; Humans; Hyperglycemia; Hyperlipidemias; Male; Metabolic Diseases; Middle Aged; Olanzapine; Psychotic Disorders; Schizophrenia

Antipsychotic medications are associated with an increased risk of diabetes. Previous studies have also found an increased risk of type 2 diabetes mellitus in the relatives of schizophrenia probands. The aim of this study was to explore the metabolic adverse effects of olanzapine in a cohort of patients with newly diagnosed psychosis and minimal or no exposure to antipsychotics. Patients with newly diagnosed psychosis (n = 30) were enrolled in a 16-week open trial of olanzapine. Body mass index, fasting glucose, hemoglobin A1c, fasting insulin, IL-6, and a fasting lipid profile were measured at baseline and at 4-week intervals. There was a significant, linear increase over time in fasting glucose (P = 0.043), weight (P < 0.001), body mass index (P < 0.001), total cholesterol (P = 0.005), triglycerides (P = 0.003), and low-density lipoprotein (P = 0.013), but not hemoglobin A1c (P = 0.691), fasting insulin (P = 0.690), IL-6 (P = 0.877), or high-density lipoprotein (P = 0.446). An abnormal baseline IL-6 was a significant predictor of a greater increase in both total cholesterol (P < 0.01) and low-density lipoprotein (P < 0.01). Otherwise, neither parental history of type 2 diabetes mellitus nor baseline IL-6 predicted changes in metabolic measures. Changes in metabolic measures with olanzapine treatment can be detected early in the treatment of patients who are previously antipsychotic naive. The absence of a change in fasting insulin suggests a failure of pancreatic islet cells to compensate for the increase in fasting glucose.

Topics: Adolescent; Adult; Benzodiazepines; Blood Glucose; Cohort Studies; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Interleukin-6; Male; Middle Aged; Olanzapine; Predictive Value of Tests; Psychotic Disorders; Young Adult

Comparisons of diabetic potential, glucose related metabolic levels, and insulin resistance between olanzapine and risperidone have produced variable results in cross-sectional and epidemiologic studies. Randomized prospective studies of metabolic effects during treatment with these drugs may provide results that are more informative.. Hospitalized patients with chronic schizophrenia (DSM-IV), most of whom had been treated with multiple antipsychotics in the past, were randomly assigned to treatment with a single antipsychotic, olanzapine or risperidone, for a period of 5 months. At baseline and every treatment month thereafter, fasting glucose, insulin, insulin-related metabolic measures, and prolactin were assessed, and an oral glucose tolerance test (OGTT) was performed during baseline and months 1, 2, and 5 of treatment. Weight was assessed monthly, and waist and hip measures were taken at baseline and month 5. Data were analyzed on 23 patients randomly assigned to risperidone and 23 patients randomly assigned to olanzapine. The study was conducted from February 2003 to August 2007.. Most patients were overweight or obese at baseline (mean body mass index [BMI] = 29.4), but there were no differential drug effects on weight change and no differences between drug groups at the 5-month time point. There were no overall drug treatment differences in fasting glucose or glycohemoglobin or 2-hour glucose levels in OGTT and no differences between the two drug groups at the 5-month time point. There were no consistent drug treatment differences in the number of patients who developed borderline or diabetic glucose levels. Olanzapine-treated patients showed a significantly greater increase than risperidone-treated patients in a fasting measure of insulin resistance (P = .041), and olanzapine patients showed greater decreases in insulin sensitivity during OGTT (P = .023) compared to risperidone-treated patients. Olanzapine-treated patients had a significantly greater increase in 1-hour glucose and insulin levels during OGTT in subsequent months compared to baseline and greater increase in glucose and insulin area under the curve over time than the risperdone-treated patients. Prolactin levels decreased in olanzapine patients and increased in risperidone patients (P values approximately .02). There were no significant drug treatment differences in C-peptide levels or 2 indices proposed as measures of insulin secretion or beta-cell function (homeostasis model assessment of beta-cell function [HOMA-B], BIGTT-acute insulin response surrogate measure [BIGTT-AIR]). Changes in insulin resistance over time were not strongly related to changes in BMI or waist circumference during study drug treatment.. The increase in insulin levels during olanzapine treatment may compensate for the increase in insulin resistance and serve to reduce fasting and postprandial glucose levels. This may contribute to the lack of differences between olanzapine and risperidone in indices of diabetic or prediabetic glucose levels or glycohemoglobin. How many years this compensatory mechanism will persist needs further investigation. Periodic OGTT tests measuring glucose and insulin levels would be helpful in assessing the status of beta-cell insulin reserve in patients treated with olanzapine and other second-generation antipsychotics and assessing an individual patient's risk for conversion to type 2 diabetes.. clinicaltrials.gov Identifier NCT00287820.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Mass Index; Chronic Disease; Diabetes Mellitus, Type 2; Female; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Insulin-Secreting Cells; Longitudinal Studies; Male; Middle Aged; Olanzapine; Prolactin; Risk Factors; Risperidone; Schizophrenia

The use of certain atypical antipsychotics has been associated with metabolic disturbances. We have assessed the evolution of body weight and glycaemia during a 6-month randomized comparative trial of amisulpride and olanzapine. Three hundred and seventy-seven adult patients with schizophrenia were randomized to either amisulpride (200-800 mg/day) or olanzapine (5-20 mg/day) for 6 months. Body weight and fasting blood glucose were measured. Both treatments showed comparable antipsychotic activity. Weight gain over the study was significantly greater (P=0.0004) in the olanzapine group (3.9+/-5.3 kg) than in the amisulpride group (1.6+/-4.9 kg). Mean fasting blood glucose increased in the olanzapine group by 4.42 mg/dl to a mean maximum value (118+/-38 mg/dl). In the amisulpride group, mean glucose levels fell by 2.82 mg/dl. The difference between groups was significant at 2 (P=0.0066) and 6 months (P=0.017). One olanzapine-treated patient was diagnosed with diabetes. Metabolic changes in the amisulpride group were restricted to patients with high body mass index at inclusion. At doses that provide comparable control of psychosis, treatment with olanzapine was associated with greater increase in weight and blood glucose compared with amisulpride. This should be taken into account in assessing risk-benefit of treatment options in schizophrenia.

Topics: Adult; Amisulpride; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Risk Factors; Schizophrenia; Sulpiride

This study examined the main metabolic side effects induced by antipsychotic treatment in a cohort of first-episode drug-naive subjects.. A randomized, open-label, prospective clinical trial was conducted. Participants were 145 consecutive subjects included in a first-episode psychosis program (PAFIP) from February 2002 to February 2005, experiencing their first episode of psychosis (DSM-IV codes 295, 297, and 298), and never treated with antipsychotic medication. Patients were assigned to haloperidol, olanzapine, or risperidone treatment during 12 weeks. The main outcome measures were changes at 12 weeks in body weight; body mass index; and 12-hours-fasting morning levels of total cholesterol, tri-glycerides, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, glucose, homeostasis model assessment (HOMA) index, and insulin.. At the endpoint, 128 patients were evaluated (88.3%). The mean doses were haloperidol = 4.2 mg/day, olanzapine = 12.7 mg/day, and risperidone = 3.6 mg/day. A significant weight gain was observed with the 3 antipsychotics: haloperidol = 3.8 (SD = 4.9) kg, olanzapine = 7.5 (SD = 5.1) kg, and risperidone = 5.6 (SD = 4.5) kg. Metabolic parameters showed a worsening lipid profile with the 3 treatments (statistically significant increase in total cholesterol and LDL cholesterol levels). Only the olanzapine group showed significant increases in triglyceride levels. After the 12-week study period, there were no significant changes in parameters involving glucose metabolism for any group.. Drug-naive patients experienced an extraordinary weight gain with first- and second-generation antipsychotics after the first 12 weeks of treatment. Significant increases in total cholesterol and LDL cholesterol levels are associated with the 3 treatments. Weight gain and metabolic disturbances induced by antipsychotics may increase the risk of developing cardiovascular disease.

Topics: Adolescent; Adult; Anthropometry; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Mass Index; Cohort Studies; Diabetes Mellitus, Type 2; Diagnostic and Statistical Manual of Mental Disorders; Dyslipidemias; Female; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Prevalence; Prospective Studies; Psychotic Disorders; Risperidone; Severity of Illness Index; Weight Gain

To assess whether metformin prevents body weight gain (BWG) and metabolic dysfunction in patients with schizophrenia who are treated with olanzapine.. Forty patients taking olanzapine (10 mg daily) were randomly allocated to a metformin (n = 20; 850 to 1700 mg daily) or placebo (n = 20) group in a 14-week double-blind study. Waist circumference (WC), BWG, body mass index (BMI) fasting glucose, insulin, and lipids were evaluated at baseline and at Weeks 7 and 14 of treatment.. At Week 14, BWG (kg) was similar in the metformin group (5.5 kg) and the placebo group (6.3 kg), P = 0.4. There were no differences between the changes in BMI, WC, glucose, insulin, insulin resistance index (HOMA-IR), and plasma lipid levels observed in the treatment group and the placebo group; however, glucose levels decreased significantly after metformin administration (P = 0.02). The HOMA-IR decreased significantly in both groups, but 3 subjects from the placebo group developed fasting glucose levels greater than 5 mmol/L. After taking metformin, triglyceride levels increased, but the cholesterol profile improved significantly.. Metformin did not prevent olanzapine-induced BWG. While some lipid parameters worsened during placebo, the HOMA-IR improved in both the placebo and the metformin groups. Carbohydrate metabolism impairment was not systematically observed during short-term olanzapine administration.

Topics: Adult; Anthropometry; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Humans; Hypercholesterolemia; Hypoglycemic Agents; Insulin Resistance; Male; Metformin; Middle Aged; Obesity; Olanzapine; Schizophrenia; Weight Gain

In order to estimate the degree of glucose tolerance impairment, oral glucose tolerance test was conducted in the group of 15 schizophrenic patients taking olanzapine, the group of 15 schizophrenic patients taking risperidone and in the group of 14 healthy volunteers. In the olanzapine group the tolerance was impaired in 33% of the patients, contrary to the risperidone group in which impairment amounted to 20% of the patients. The authors discuss possible mechanisms responsible for impaired glucose tolerance in patients taking newer antipsychotic drugs.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glucose Tolerance Test; Humans; Hyperglycemia; Insulin Resistance; Male; Middle Aged; Olanzapine; Risk; Risperidone

Second-generation antipsychotics (SGAs), used as the cornerstone treatment for schizophrenia and other mental disorders, can cause adverse metabolic effects (e.g. obesity and type 2 diabetes). We investigated the effects of SGAs on adipocyte differentiation and metabolism. The presence of therapeutic concentrations of aripiprazole (ARI) or its active metabolite dehydroaripiprazole (DARI) during human adipocyte differentiation impaired adipocyte glucose uptake while the expression of gene markers of fatty acid oxidation were increased. Additionally, the use of a supra-therapeutic concentration of ARI inhibited adipocyte differentiation. Furthermore, olanzapine (OLA), a highly obesogenic SGA, directly increased leptin gene expression but did not affect adipocyte differentiation and metabolism. These molecular insights are novel, and suggest that ARI, but not OLA, may directly act via alterations in adipocyte differentiation and potentially by causing a switch from glucose to lipid utilization in human adipocytes. Additionally, SGAs may effect crosstalk with other organs, such as the brain, to exert their adverse metabolic effects.

Topics: Adipocytes; Antipsychotic Agents; Aripiprazole; Diabetes Mellitus, Type 2; Humans; Olanzapine; Piperazines

Second-generation antipsychotic (SGA) drugs have been associated with the development of type 2 diabetes and the metabolic syndrome in patients with schizophrenia. In this study, we aimed to investigate the effects of two different SGA drugs, olanzapine and aripiprazole, on metabolic state and islet function and plasticity.. We analysed the functional adaptation of beta cells in 12-week-old B6;129 female mice fed an olanzapine- or aripiprazole-supplemented diet (5.5-6.0 mg kg. Both SGAs induced weight gain and beta cell dysfunction, leading to glucose intolerance; however, aripiprazole had a more potent effect in terms of metabolic alterations, which was likely a result of its ability to modulate the serotonergic system. The deleterious metabolic effects of SGAs on islet function should be considered while treating patients as these drugs may increase the risk for development of the metabolic syndrome and diabetes.

Topics: Animals; Antipsychotic Agents; Aripiprazole; Diabetes Mellitus, Type 2; Female; Humans; Islets of Langerhans; Mice; Olanzapine

Topics: Anthocyanins; Diabetes Mellitus, Type 2; Elaeocarpaceae; Fatty Liver; Glucosides; Hep G2 Cells; Hepatocytes; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Lipid Metabolism; Lipids; Liver; Muscle Fibers, Skeletal; Muscle, Skeletal; Obesity; Olanzapine; Plant Extracts; Polyphenols

Antipsychotic use is associated with an increased risk of type 2 diabetes. Recent work suggests antipsychotics can induce insulin resistance immediately and independently of weight gain, and that this may occur via the central nervous system (CNS). We have previously shown that the highly effective and widely prescribed antipsychotic, olanzapine inhibits CNS insulin-mediated suppression of hepatic glucose production, but the mechanisms remain unknown. The ATP-sensitive potassium (K

Topics: Adenosine Triphosphate; Diabetes Mellitus, Type 2; Glucose; Humans; Insulin; Insulin Resistance; Olanzapine

Olanzapine is effective for schizophrenia management; however, it is contraindicated in diabetes patients. In addition, olanzapine is useful for treating nausea and vomiting, such as in the case of chemotherapy-induced nausea and vomiting (CINV). Therefore, we hypothesized that the contraindicated prescription of olanzapine likely occurs among cancer patients with diabetes, especially by non-psychiatric physicians. Hence, we conducted a nationwide survey to elucidate the situation of such contraindicated prescriptions and the associated risk factors. We extracted the data of patients who were newly prescribed olanzapine between April 2015 and March 2017 from the health insurance claims database developed by JMDC, Inc., Tokyo. The patients who were prescribed contraindicated olanzapine were defined as those who were prescribed olanzapine after a diagnosis of diabetes and diabetes drug prescription. In all, the data of 7181 patients were analyzed. We evaluated the proportion of diabetes patients who were prescribed contraindicated olanzapine from among those who were prescribed olanzapine. Furthermore, we investigated the background of patients who were prescribed olanzapine for information such as olanzapine prescribers and history of cancer chemotherapy. In all, 100 diabetes patients (1.39%) were prescribed olanzapine. In these patients, the frequency of olanzapine prescription was higher by non-psychiatry/neurology physicians than by psychiatry/neurology physicians (3.25 and 0.85%, respectively). Additionally, all olanzapine prescriptions in cancer chemotherapy-treated diabetes patients were issued by non-psychiatry/neurology physicians. Thus, our study revealed there were diabetes patients who were prescribed olanzapine. Additionally, olanzapine for CINV management was more likely to be a contraindicated prescription.

Topics: Adult; Antiemetics; Antineoplastic Agents; Antipsychotic Agents; Contraindications, Drug; Databases, Factual; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Japan; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Risk Factors; Schizophrenia; Vomiting

Atypical antipsychotics such as olanzapine often induce excessive weight gain and type 2 diabetes. However, the mechanisms underlying these drug-induced metabolic perturbations remain poorly understood. Here, we used an experimental model that reproduces olanzapine-induced hyperphagia and obesity in female C57BL/6 mice. We found that olanzapine treatment acutely increased food intake, impaired glucose tolerance, and altered physical activity and energy expenditure in mice. Furthermore, olanzapine-induced hyperphagia and weight gain were blunted in mice lacking the serotonin 2C receptor (HTR2C). Finally, we showed that treatment with the HTR2C-specific agonist lorcaserin suppressed olanzapine-induced hyperphagia and weight gain. Lorcaserin treatment also improved glucose tolerance in olanzapine-fed mice. Collectively, our studies suggest that olanzapine exerts some of its untoward metabolic effects via antagonism of HTR2C.

Topics: Animals; Antipsychotic Agents; Benzodiazepines; Body Composition; Body Weight; Diabetes Mellitus, Type 2; Female; Glucose; Glucose Tolerance Test; Hyperphagia; Male; Mice; Mice, Inbred C57BL; Olanzapine; Receptor, Serotonin, 5-HT2C; Serotonin Antagonists; Weight Gain

There is limited, poorly characterized information about adverse events occurring during maintenance treatment of bipolar disorder. We aimed to determine adverse event rates during treatment with lithium, valproate, olanzapine, and quetiapine.. We conducted a propensity score adjusted cohort study using nationally representative United Kingdom electronic health records from January 1, 1995, until December 31, 2013. We included patients who had a diagnosis of bipolar disorder and were prescribed lithium (n = 2148), valproate (n = 1670), olanzapine (n = 1477), or quetiapine (n = 1376) as maintenance mood stabilizer treatment. Adverse outcomes were chronic kidney disease, thyroid disease, hypercalcemia, weight gain, hypertension, type 2 diabetes mellitus, cardiovascular disease, and hepatotoxicity. The propensity score included important demographic, physical health, and mental health predictors of drug treatment allocation. The median duration of drug treatment was 1.48 y (interquartile range 0.64-3.43). Compared to patients prescribed lithium, those taking valproate, olanzapine, and quetiapine had reduced rates of chronic kidney disease stage 3 or more severe, following adjustment for propensity score, age, and calendar year, and accounting for clustering by primary care practice (valproate hazard ratio [HR] 0.56; 95% confidence interval [CI] 0.45-0.69; p < 0.001, olanzapine HR 0.57; 95% CI 0.45-0.71; p < 0.001, quetiapine HR 0.62; 95% CI 0.47-0.80; p < 0.001). Hypothyroidism was reduced in those taking valproate (HR 0.60; 95% CI 0.40-0.89; p = 0.012) and olanzapine (HR 0.48; 95% CI 0.29-0.77; p = 0.003), compared to those taking lithium. Rates of new onset hyperthyroidism (valproate HR 0.24; 95% CI 0.09-0.61; p = 0.003, olanzapine HR 0.31; 95% CI 0.13-0.73; p = 0.007) and hypercalcemia (valproate HR 0.25; 95% CI 0.10-0.60; p = 0.002, olanzapine HR 0.32; 95% CI 0.14-0.76; p = 0.008, quetiapine HR 0.23; 95% CI 0.07-0.73; p = 0.013) were also reduced relative to lithium. However, rates of greater than 15% weight gain on valproate, olanzapine, and quetiapine were higher (valproate HR 1.62; 95% CI 1.31-2.01; p < 0.001, olanzapine HR 1.84; 95% CI 1.47-2.30; p < 0.001, quetiapine HR 1.67; 95% CI 1.24-2.20; p < 0.001) than in individuals prescribed lithium, as were rates of hypertension in the olanzapine treated group (HR 1.41, 95% CI 1.06-1.87; p = 0.017). We found no significant difference in rates of chronic kidney disease stage 4 or more severe, type 2 diabetes mellitus, cardiovascular disease, or hepatotoxicity. Despite estimates being robust following sensitivity analyses, limitations include the potential for residual confounding and ascertainment bias and an inability to examine dosage effects.. Lithium use is associated with more renal and endocrine adverse events but less weight gain than commonly used alternative mood stabilizers. Risks need to be offset with the effectiveness and anti-suicidal benefits of lithium and the potential metabolic side effects of alternative treatment options.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cardiovascular Diseases; Chemical and Drug Induced Liver Injury; Cohort Studies; Diabetes Mellitus, Type 2; Female; Humans; Hypercalcemia; Hypertension; Lithium Compounds; Longitudinal Studies; Male; Middle Aged; Olanzapine; Propensity Score; Quetiapine Fumarate; Renal Insufficiency; Thyroid Diseases; Valproic Acid

Insulin-induced insulin receptor (IR) tyrosine kinase activation and insulin cell survival responses have been reported to be under the regulation of a membrane associated mammalian neuraminidase-1 (Neu1). The molecular mechanism(s) behind this process is unknown. Here, we uncover a novel Neu1 and matrix metalloproteinase-9 (MMP-9) cross-talk in alliance with neuromedin B G-protein coupled receptor (GPCR), which is essential for insulin-induced IR activation and cellular signaling. Neu1, MMP-9 and neuromedin B GPCR form a complex with IRβ subunit on the cell surface. Oseltamivir phosphate (Tamiflu®), anti-Neu1 antibodies, broad range MMP inhibitors piperazine and galardin (GM6001), MMP-9 specific inhibitor (MMP-9i), and GPCR neuromedin B specific antagonist BIM-23127 dose-dependently inhibited Neu1 activity associated with insulin stimulated rat hepatoma cells (HTCs) that overly express human IRs (HTC-IR). Tamiflu, anti-Neu1 antibodies and MMP-9i attenuated phosphorylation of IRβ and insulin receptor substrate-1 (IRS1) associated with insulin-stimulated cells. Olanzapine, an antipsychotic agent associated with insulin resistance, induced Neu3 sialidase activity in WG544 or 1140F01 human sialidosis fibroblast cells genetically defective in Neu1. Neu3 antagonist 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (DANA) and anti-Neu3 antibodies inhibited sialidase activity associated with olanzapine treated murine Neu4 knockout macrophage cells. Olanzapine attenuated phosphorylation of IGF-R and IRS1 associated with insulin-stimulated human wild-type fibroblast cells. Our findings identify a novel insulin receptor-signaling platform that is critically essential for insulin-induced IRβ tyrosine kinase activation and cellular signaling. Olanzapine-induced Neu3 sialidase activity attenuated insulin-induced IGF-R and IRS1 phosphorylation contributing to insulin resistance.

Topics: Animals; Antipsychotic Agents; Benzodiazepines; Cell Line, Tumor; Diabetes Mellitus, Type 2; Humans; Insulin; Insulin Receptor Substrate Proteins; Insulin Resistance; Matrix Metalloproteinase 9; Mice; Neuraminidase; Olanzapine; Phosphorylation; Protein Processing, Post-Translational; Protein Transport; Rats; Receptor, IGF Type 1; Receptor, Insulin; Signal Transduction

Atypical antipsychotics are the main treatment for a large number of psychiatric illnesses, with fewer extrapyramidal effects than conventional antipsychotics. However, it has been suggested that their use is associated with increased risk of dyslipidemia and type 2 diabetes mellitus.. The risk of metabolic adverse effects associated with asenapine was assessed in comparison with that associated with olanzapine using real-world data.. This study was a retrospective analysis based on data extracted from the Italian and Spanish Cegedim Strategic Data Longitudinal Patient-Data databases. Patients with asenapine or olanzapine prescriptions were retrieved from September 2010 to December 2012 using strict inclusion criteria to guarantee minimization of confounders. Patients with type 2 diabetes mellitus and dyslipidemia were identified by using ICD9 codes and by antidiabetic and dyslipidemic drug prescriptions. The presence or absence of the metabolic condition was compared before and after treatment, and between cohorts.. The retrospective analysis showed a lower risk of developing type 2 diabetes with asenapine than with olanzapine (2.2 vs 3.5%, respectively; p value: 0.0002) and of developing dyslipidemia (2.8 vs 6.8%, respectively; p value: 0.0001).. Asenapine is associated with a lower risk of metabolic adverse effects than olanzapine, demonstrating its improved safety profile.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cohort Studies; Diabetes Mellitus, Type 2; Dibenzocycloheptenes; Dyslipidemias; Female; Heterocyclic Compounds, 4 or More Rings; Humans; Italy; Male; Mental Disorders; Middle Aged; Olanzapine; Retrospective Studies; Spain

This study aims to explore and analyze the condition of concurrent diseases and medicine use of traditional Chinese medicine (TCM) and western medicine among the patients with insomnia. One thousand and sxity seven cases of data from 20 national hospitals' hospital information system (HIS) databases were collected. The frequent concurrent diseases included hypertension (26.9%), brain blood supply insufficiency (24.93%), cerebral infarction (19.49%), blood lipoprotein disturbance (15.28%), coronary heart disease (14.15%), headache (10.68%), chronic gastritis (8.81%), type 2 diabetes mellitus (7.87%), depressive disorder (7.4%) and anxiety disorder (6.65%). The 10 most frequently-used western drugs included alprazolam (35.99%), aspirin (25.4%), olanzapine (24.18%), cinepazide (23.06%), flupentixol & melitracen (18.74%), zolpidem (18.37%), oxiracetam (15.65%), estazolam (15%), aniracetam (13.4%) and piracetam (13.31%). The 10 most frequently-used TCM included Shuxuening injection (16.4%), Shuxuetong injection (15.18%), extract of ginkgo biloba leaf (14.71%), gastrodin (12.46%), Dengzanxixin injection (11.34%), Xueshuantong (8.53%), Danhong injection (6.37%), compound liquorice tablet (5.81%), Sanqi Tongshu capsule (5.72%) and sowthistle-leaf ixeridium injection (5.34%). Among all combined uses, the most frequent western drug use was alprazolam and olanzapine, while combined use of hypnotic drug and Huoxuehuayu formula is the most frequent. This study concludes that the concurrent diseases mainly include cardio-cerebrovascular diseases, metabolic disorders and anxiety-depression disorders, with increasing tendency of diseases types by ages, especially for cardio-cerebrovascular diseases. The most frequently-used hypnotic is alprazolam in the insomnia patients, and it is worth being concerned about the off-label use of olanzapine as an antipsychotic for the treatment of insomnia However, due to the fact that all cases data are from the inpatients, these findings have some limitations.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Alprazolam; Anti-Anxiety Agents; Antipsychotic Agents; Benzodiazepines; Cerebral Infarction; Coronary Disease; Diabetes Mellitus, Type 2; Drugs, Chinese Herbal; Female; Headache; Humans; Hypertension; Male; Medicine, Chinese Traditional; Middle Aged; Olanzapine; Sleep Initiation and Maintenance Disorders; Young Adult

The association between the use of antipsychotics and diabetes mellitus (DM) is still unclear, as depicted by several conflicting reports. Our study aims to assess the risk of DM in new users of antipsychotics.. Our nested case-control study used the Quebec Health Insurance Board databases. People in the source cohort were DM-free and had initiated an antipsychotic treatment. Subjects were cohort members who initiated an antidiabetic or had a diagnosis of DM during their follow-up period. Three variables were used to assess antipsychotic exposure: the antipsychotic used (any typical, clozapine, olanzapine, quetiapine, risperidone, or more than 1 drug); the number of 30-day periods of use; and antipsychotic use at index date (current or past). A paired multivariate logistic regression model was used to calculate adjusted odds ratios.. Among the 88 467 people included in the cohort, 6109 subjects with DM were identified and were matched to 61 090 control subjects. New users of quetiapine were less likely to develop DM than new users of typical antipsychotics (OR, 0.89; 95% CI 0.81 to 0.99). The risk of DM was not statistically different across the atypical antipsychotics. A longer exposure to any antipsychotic (for each 30-day period, OR 1.009; 95% CI 1.006 to 1.011) and current use of antipsychotics (OR 1.26; 95% CI 1.17 to 1.36) were associated with DM.. These results suggest that metabolic parameters of people exposed to antipsychotics should be monitored, irrespective of the drug taken, among the drugs available at the time of analysis.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Case-Control Studies; Clozapine; Cohort Studies; Diabetes Mellitus, Type 2; Dibenzothiazepines; Female; Humans; Logistic Models; Male; Middle Aged; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risperidone; Time Factors; Young Adult

Second-generation antipsychotics (SGAs) increase the risk of type 2 diabetes. The mechanism is thought to center on drug-induced weight gain, which starts the dysmetabolic cascade of insulin resistance, increased insulin production and pancreatic beta-cell failure. An independent effect of SGAs on insulin secretion has been suggested in animal models, but has not been demonstrated in clinical samples.. To determine the post-challenge insulin secretion in patients treated with SGAs.. We identified 520 non-diabetic individuals treated with clozapine (N=73), olanzapine (N=190), quetiapine (N=91) or risperidone (N=166) in a consecutive, single-site cohort of 783 adult psychiatric inpatients who underwent a comprehensive metabolic assessment. Insulin secretion was measured as the area under the curve (AUC(insulin)) generated by levels recorded at baseline, 30, 60 and 120 min after the intake of 75 g of glucose. The independent predictors of insulin secretion were determined with regression analysis in the entire sample and separately in patients with normal glucose tolerance (NGT) and prediabetes.. The post-challenge AUC(insulin) was independently predicted by AUC(glucose), waist circumference, triglyceride levels and younger age (p<0.0001); non-smoking status (p=0.0012); and treatment with clozapine (p=0.021). The model explained 33.5% of the variance in insulin secretion (p<0.0001). The clozapine effect was present in the NGT group, but not in prediabetics.. Clozapine, but not olanzapine, quetiapine and risperidone, is an independent predictor of post-challenge insulin secretion in non-diabetics, particularly in those with normal glucose tolerance. The findings suggest that the diabetogenic risk of clozapine may persist even after weight reduction.

Topics: Adult; Antipsychotic Agents; Area Under Curve; Benzodiazepines; Clozapine; Diabetes Mellitus, Type 2; Dibenzothiazepines; Female; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Olanzapine; Predictive Value of Tests; Quetiapine Fumarate; Regression Analysis; Risperidone

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Middle Aged; Olanzapine; Risperidone; Schizophrenia; Withholding Treatment

Previous studies have demonstrated an association between certain second-generation antipsychotics (SGAs) and diabetes mellitus. The study assessed the impact of SGA dose on hemoglobin A1C (HbA(1c) >6.0) levels in a real-world setting. Patients aged ≥ 18 years during 2002-2006 in Ingenix LabRx claims database were included. The database collects medical and prescription claims and a subset of laboratory results for an employed, commercially insured population distributed throughout the United States. Patients with previously diagnosed diabetes, identified by the ICD-9-CM code of 250.x or use of antidiabetic agents, were excluded. The main exposure measure was the cumulative dose over a 30 day period before the HbA(1c) test, calculated as [sum of (number of pills per day×strength)]/100. A logistic regression was used to examine the relation with HbA(1c) >6.0 by tertile of the cumulative dose and average daily dose, adjusted for the covariates. The study included 391 patients on olanzapine, 467 on quetiapine, and 262 on risperidone. Patients treated with aripiprazole or ziprasidone (n=212) were included as a secondary reference because of their minimal metabolic risk. Compared to lower (Tertiles 1 and 2) cumulative doses of risperidone, patients with a high cumulative dose of risperidone (Tertile 3) had a significantly higher odds ratio (OR) for HbA(1c) >6.0 (adjusted OR=2.45; 95% confidence interval=1.13-5.32; P=0.023). A similar increase in OR was seen in patients with high cumulative dose of olanzapine (2.41; 1.19-4.89; P=0.015). Analyses of average daily dose revealed that quetiapine ≥ 400 mg/day and risperidone ≥ 2 mg/day had an OR of 2.29 (1.04-5.06; P=0.041) and 2.28 (1.08-4.83; P=0.032), respectively, compared to aripiprazole/ziprasidone. Both olanzapine groups (≥ 10 and <10mg/day) were associated with a significantly increased OR. All results remained similar after further adjustment for the predicated probability of having an HbA(1c) test and additional medication covariates. In this claims data study, use of olanzapine was associated with elevated HbA(1c) and risperidone and quetiapine appeared to have dose-related association with elevated HbA(1c). One of the limitations of a claims data analysis is the lack of information on potential confounders such as ethnicity and weight.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Databases, Factual; Diabetes Mellitus, Type 2; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Prescriptions; Female; Glycated Hemoglobin; Hemoglobins; Humans; Hypoglycemic Agents; Male; Middle Aged; Olanzapine; Quetiapine Fumarate; Retrospective Studies; Risperidone; Time Factors; United States

Although the relationship between antipsychotic medication, particularly second-generation antipsychotics (SGAs), and metabolic disturbance is increasingly accepted, there is an important, but little recognised, potential interaction between this and the other important serious adverse effect of neuroleptic malignant syndrome (NMS). We report a case of a 35-year old female who developed new onset type II diabetes mellitus with hyperosmolar hyperglycaemic coma and acute renal failure following treatment with a SGA for a first manic episode. The history is strongly suggestive of concurrent NMS. This case raises important questions about non-ketotic, hyperosmolar diabetic coma with antipsychotics, the possible association between hyperglycaemia and hyperthermia, and the direction of causality in this, the recognition of either syndrome when they co-exist and management issues in such patients. These questions are considered in the context of currently available literature.

Topics: Acute Kidney Injury; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Diabetes Mellitus, Type 2; Female; Humans; Hyperglycemic Hyperosmolar Nonketotic Coma; Neuroleptic Malignant Syndrome; Olanzapine

The effect of risperidone and olanzapine on beta-cell function and mass was investigated in 90% pancreatectomized and ovariectomized female rats, of which some were treated with estrogen replacement and some were not. Ovariectomized diabetic rats were divided into two groups: one group received daily estrogen replacement (30 mug 17beta-estradiol/kg body weight) and the other group received a vehicle. Each group was further divided into three subgroups and orally given either a placebo, risperidone (0.5 mg/kg body weight), or olanzapine (2 mg/kg body weight) each day in conjunction with a high-fat diet for eight weeks. Ovariectomy reduced serum prolactin levels, while risperidone and estrogen replacement increased them. Olanzapine, not risperidone, increased body weight gain and epididymal fats, and impaired glucose tolerance in ovariectomized diabetic rats, while estrogen replacement improved them. This was related to changes in insulin secretion capacity. Ovariectomized rats had decreased beta-cell mass, due to decreasing beta-cell proliferation, compared with Sham rats, and olanzapine, but not risperidone, caused further reduction. Olanzapine reduced IRS2 protein levels in the islets of ovariectomized rats. Decreased IRS2 attenuated the phosphorylation of Akt and, subsequently, PDX-1 protein levels were lowered in olanzapine-treated rats. Estrogen replacement activated insulin/IGF-1 signaling regardless of treatment. In conclusion, olanzapine, but not risperidone, exacerbated glucose homeostasis partly by attenuating beta-cell function and mass in ovariectomized diabetic rats, while estrogen replacement reversed its negative impact. Further human studies are needed to support the claim that olanzapine should be avoided in the treatment of schizophrenic postmenopausal patients with diabetes.

Topics: Adipose Tissue; Animals; Antipsychotic Agents; Benzodiazepines; Blotting, Western; Cell Separation; Cell Survival; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Estradiol; Estrogen Replacement Therapy; Female; Glucose; Glucose Tolerance Test; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Insulin-Secreting Cells; Olanzapine; Ovariectomy; Pancreatectomy; Prolactin; Rats; Rats, Sprague-Dawley; Risperidone; Weight Gain

We investigated whether estrogen replacement modulated energy and glucose metabolic changes induced by olanzapine (OZP) and risperidone (RPD) in 90% pancreatectomized diabetic rats, some of whom had also been ovariectomized (OVX) and some of whom had not (sham).. OVX diabetic rats were subcutaneously injected with estrogen replacement (17beta-estradiol, 30 microg/kg/day) or a vehicle. Each group was divided into 3 subgroups, and each subgroup was orally either given a placebo, RPD (0.5 mg/kg body weight/day) or OZP (2 mg/kg body weight/day) for 8 weeks. Sham rats were also divided into 3 subgroups and given drugs in the same manner as the OVX rats were. All rats were fed high-fat diets.. OZP increased body weight and epididymal fat pads more than the control (vehicle) in sham and OVX rats. Increased body weight in OZP-treated sham and OVX rats was due to the increment in food intake, which was associated with potentiating the phosphorylation of hypothalamic adenosine-monophosphate-activated protein kinase. At euglycemic hyperinsulinemic clamping, OZP decreased glucose infusion rates and increased hepatic glucose output in OVX diabetic rats. In sham rats, OZP increased hepatic glucose output but not as much as in OVX rats. Hepatic insulin signaling and glucose sensing were attenuated in OZP-treated OVX rats, and the attenuation increased hepatic phosphoenolpyruvate carboxykinase expression to induce gluconeogenesis. These negative and harmful effects noted among OZP-treated OVX rats were reversed by estrogen replacement treatment. However, RPD did not alter body weight and peripheral insulin sensitivity in sham and OVX rats.. OZP treatment should be avoided when treating diabetic and schizophrenic women, especially those in their postmenopausal period.

Topics: Adipose Tissue; Animals; Antipsychotic Agents; Benzodiazepines; Diabetes Mellitus, Type 2; Eating; Estradiol; Estrogen Replacement Therapy; Female; Glucose; Insulin Resistance; Liver; Olanzapine; Ovariectomy; Pancreatectomy; Random Allocation; Rats; Rats, Sprague-Dawley; Risperidone; Weight Gain

Diabetes mellitus occurs in schizophrenia patients at higher rates than in the general population. Reasons for this elevated risk are poorly understood and have not been examined prospectively in antipsychotic-naïve, first-episode patients. This study aims to determine which antipsychotics are associated with diabetes development in antipsychotic-naïve schizophrenia patients. All antipsychotic-naïve patients diagnosed with schizophrenia in Denmark between 01 January 1997 and 31 December 2004, followed until 31 December 2007, allowing for >or=3 years follow-up, unless death or diabetes onset occurred. Risk factors for the time to diabetes onset were assessed, including antipsychotics taken for at least 180 defined daily doses in the first year after first antipsychotic prescription ('initial treatment'). Risk factors for diabetes incidence were assessed, including antipsychotic use within 3 months before diabetes onset or study end ('current treatment'). Of 7139 patients, followed for 6.6 years (47,297 patient years), 307 developed diabetes (annual incidence rate: 0.65%). Time to diabetes onset was significantly shorter in patients with higher age (hazard ratio (HR): 1.03, confidence interval (CI): 1.02-1.03) and those with 'initial' treatment of olanzapine (HR: 1.41, CI: 1.09-1.83), mid-potency first-generation antipsychotics (FGAs) (HR: 1.60, CI: 1.07-2.39), antihypertensive (HR: 1.87, CI: 1.13-3.09), or lipid-lowering drugs (HR: 4.67, CI: 2.19-10.00). Significant factors associated with diabetes within 3 month of its development included treatment with low-potency FGAs (odds ratio (OR): 1.52, CI: 1.14-2.02), olanzapine (OR: 1.44, CI: 1.98-1.91), and clozapine (OR: 1.67, CI: 1.14-2.46), whereas aripiprazole was associated with lower diabetes risk (OR: 0.51, CI: 0.33-0.80). In addition to general diabetes risk factors, such as age, hypertension, and dyslipidemia, diabetes is promoted in schizophrenia patients by initial and current treatment with olanzapine and mid-potency FGAs, as well as by current treatment with or low-potency first-generation antipsychotics and clozapine, whereas current aripiprazole treatment reduced diabetes risk. Patients discontinuing olanzapine or mid-potency FGA had no increased risk of diabetes compared with patient not treated with the drugs at anytime.

Topics: Adult; Antihypertensive Agents; Antipsychotic Agents; Benzodiazepines; Cohort Studies; Confidence Intervals; Denmark; Diabetes Mellitus, Type 2; Female; Gene Expression Regulation; Humans; Incidence; Male; Olanzapine; Retrospective Studies; Risk Factors; Schizophrenia; Time Factors

Atypical antipsychotics are increasingly replacing conventional neuroleptic agents, but induction of impaired glucose tolerance and development of type 2 diabetes are of concern as side effects. Risperidone has been suggested to be superior to olanzapine for glucose tolerance in whites, but there is little information on these drugs in Asian populations, even though Asians have a higher risk of type 2 diabetes compared to whites.. A 75-g oral glucose tolerance test (OGTT) was performed in 100 age-matched, sex-matched, and body mass index (BMI)-matched Japanese inpatients with schizophrenia (DSM-IV criteria) who did not suffer from diabetes and had taken risperidone (N=50) or olanzapine (N=50) for at least 3 months. Subjects were from 1 university hospital and 3 mental hospitals in Japan; data were collected from April 2005 to March 2006. The same test was performed in 50 age-matched, sex-matched, and BMI-matched healthy Japanese subjects. Plasma glucose and serum insulin concentrations were measured just before loading (0 minutes) and 30, 60, and 120 minutes after oral glucose loading, and sorbitol levels in red blood cells were assayed at 0 and 120 minutes.. The fasting glucose level and insulin concentration did not differ among the risperidone, olanzapine, and control groups, but the areas under the concentration time curves for plasma glucose and serum insulin concentrations from 0 to 120 minutes in patients receiving risperidone or olanzapine were significantly higher (p<.05) than those for healthy controls. However, neither the insulinogenic index nor homeostasis model assessment of insulin resistance differed among the 3 groups. Sorbitol in red blood cells was significantly higher (p<.05) in both patient groups compared to the control group.. Olanzapine and risperidone may impair glucose tolerance due in part to increased insulin resistance. However, neither drug influenced insulin secretion in Japanese patients, and, therefore, these findings do not necessarily imply that atypical antipsychotics are directly associated with a risk of impairment of glucose tolerance.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Japan; Male; Matched-Pair Analysis; Middle Aged; Olanzapine; Risperidone; Schizophrenia

Progression of metabolic illness in a patient with schizophrenia who was stabilized on an atypical antipsychotic is described using a case study framework. Risks and benefits of staying on current treatment versus switching to another agent and switching strategies are described.. Switching an antipsychotic with more favorable side effects may improve metabolic parameters if other weight loss strategies have failed. Switching or stopping medications too quickly may exacerbate psychiatric symptoms. There is little evidence to support which is the best switching strategy.. The psychiatric mental health nurse practitioner carries a significant responsibility of discussing risks and benefits of switching and closely monitoring the patient during a switch of medications. Ensuring that the patient decides and agrees upon the treatment plan will improve the overall outcome.

Topics: Antipsychotic Agents; Benzodiazepines; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Follow-Up Studies; Humans; Hypercholesterolemia; Hypertriglyceridemia; Long-Term Care; Male; Middle Aged; Olanzapine; Paroxetine; Psychotic Disorders; Risk Assessment; Schizophrenia; Thioridazine

Adverse effects from medication vary with age. Weight gain with several psychotropics is well known in adults but less information is available related to extent and complications of psychotropic-induced weight gain in older psychiatric patients. We determined the relative incidence of 2 obesity-related conditions (diabetes and hypertension) in older psychiatric patients receiving antipsychotics, antidepressants, and mood stabilizers.. A population-based case-control study of all psychiatric patients aged 67 years or older in contact with either specialist services or primary care using administrative data from Nova Scotia.. We identified incident cases of diabetes (n = 608) and of hypertension (n = 1056), as well as an equal number of control subjects for each condition. Amitryptiline, selective serotonin reuptake inhibitors (SSRIs), and olanzapine were associated with an increased risk of presenting with hypertension 6 months after initial prescription. By contrast, conventional antipsychotics were associated with a reduced incidence of hypertension. Olanzapine was also significantly associated with diabetes after 6 months (OR adj = 2.58, 95% CI 1.12 to 5.92). The findings for SSRIs and olanzapine remained significant after adjusting for potential confounders such as sociodemographic characteristics, schizophrenia, beta blockers, thiazide diuretics, and corticosteroids.. Our results suggest that the association of psychotropics and 2 obesity-related conditions, hypertension and diabetes, applies to older psychiatric patients as well as younger populations. Within drug classes, there are drugs that have a greater association than others, and this may be a factor when choosing a specific agent.

Topics: Age Factors; Aged; Aged, 80 and over; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Chronic Disease; Diabetes Mellitus, Type 2; Female; Humans; Hypertension; Male; Mental Disorders; Obesity; Olanzapine; Psychotropic Drugs; Selective Serotonin Reuptake Inhibitors

To assess the effects of olanzapine and risperidone on metabolic factors in children and adolescents admitted to an inpatient psychiatric hospital.. The study was a retrospective chart review of hospitalized patients younger than 18 years of age treated with olanzapine or risperidone. Data collected from medical charts were analyzed to assess weight gain, lipid profiles, blood pressure, and glucose levels in patients prescribed olanzapine or risperidone.. A total of 49 patients (25 receiving olanzapine and 24 receiving risperidone) with a mean age of 13 years were included in the study; the mean duration of treatment was 27 days. A significant increase in body mass index (BMI) from baseline to endpoint in both treatment groups was found (P<0.001); however, the change in BMI was not significantly different between the olanzapine and risperidone groups (P=0.425). Seven new cases (28%) in the olanzapine group and 4 new cases (17%) in the risperidone group met criteria for being overweight or at risk for being overweight. A significant increase in mean systolic blood pressure was found in subjects receiving olanzapine compared with those receiving risperidone (+5.4 mm Hg vs. -3.2 mm Hg; P=0.044), while diastolic blood pressure did not differ between the treatment groups. A significant increase in risk factors for diabetes mellitus (P=0.008) and in overall risk factors for metabolic syndrome (P=0.013) was found in the olanzapine group over the course of treatment, whereas no significant effect on risk factors for diabetes or metabolic syndrome was found in the risperidone group.. Inpatient treatment with both olanzapine and risperidone was correlated with a significant increase in BMI. Olanzapine also resulted in increased risk factors for diabetes and metabolic syndrome.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Child; Diabetes Mellitus, Type 2; Female; Hospitalization; Hospitals, Psychiatric; Humans; Male; Metabolic Syndrome; Olanzapine; Psychotic Disorders; Retrospective Studies; Risperidone

Type 2 diabetes is a major health problem in individuals with schizophrenia. The genetic basis of diabetes risk in individuals with schizophrenia has not been previously defined. We measured polymorphisms in a human endogenous retrovirus, Herv K-18, which is located in the CD48 signaling lymphocyte activating (SLAM) gene on chromosome 1. The study population consisted of 229 individuals with schizophrenia, 29 of whom had a history of type 2 diabetes, as well as 136 control individuals without a history of a psychiatric disorder or type 2 diabetes. We found that a haplotype defined by 2 polymorphisms in the envelope region of Herv K-18 is highly associated with type 2 diabetes in a population of 229 individuals with schizophrenia, with an odds ratio of 9.0 (95% confidence limits 2.3-34.7, p<.001) adjusted for race, gender and type of antipsychotic medication. Lower levels of association were found in other polymorphisms located in the 3'untranslated region of Herv K-18 and in adjacent loci in CD48. Polymorphisms in endogenous retroviruses which are located near immunomodulatory genes may constitute risk factors for diabetes in individuals with schizophrenia.

Topics: 3' Untranslated Regions; Antigens, CD; Antipsychotic Agents; Benzodiazepines; CD48 Antigen; Chromosomes, Human, Pair 1; Clozapine; Diabetes Mellitus, Type 2; Diagnostic and Statistical Manual of Mental Disorders; Endogenous Retroviruses; Female; Haplotypes; Humans; Intracellular Signaling Peptides and Proteins; Male; Middle Aged; Olanzapine; Polymorphism, Genetic; Risk Factors; Risperidone; Schizophrenia; Signaling Lymphocytic Activation Molecule Associated Protein

Topics: Antipsychotic Agents; Benzodiazepines; Diabetes Mellitus, Type 2; Drug Administration Schedule; Humans; Hypoglycemic Agents; Metformin; Obesity; Olanzapine; Schizophrenia; Weight Loss

In recent years, several studies showed increased rates of hyperglycaemia, diabetes, dyslipidemia, metabolic syndrome as well as cardiovascular disease in schizophrenic patients. The underlying mechanism, however, is poorly understood. Adiponectin is a recently identified adipocyte-derived protein, with low adiponectin levels being associated with metabolic abnormalities such as obesity, insulin resistance and type 2 diabetes.. Fasting adiponectin levels were assessed in a cross-sectional sample of 386 patients with schizophrenia or schizoaffective disorder. All patients were on monotherapy of second-generation antipsychotics (SGA) and underwent an extensive metabolic screening including an oral glucose tolerance test (OGTT).. Adiponectin plasma levels were inversely correlated with BMI, and differed significantly between patients with normal weight, overweight or obesity (p<0.05). Patients who met criteria for the metabolic syndrome, according to adapted National Cholesterol Educational Program - Adult Treatment Panel criteria (NCEP-ATP III) (29.3%), had significantly lower adiponectin levels than patients not meeting metabolic syndrome criteria (p<0.0001). Patients without glucose abnormalities (78%) had significantly higher adiponectin levels than patients with diabetes (5.7%) (p<0.05). After controlling for components of metabolic syndrome and sex, antipsychotic medication independently influenced adiponectin levels (p<0.0001), with the lowest mean levels in patients on clozapine and olanzapine.. Adiponectin levels in schizophrenic patients mirror what is observed in the general population, with the lowest levels in the most metabolically comprised subjects. However, antipsychotic medication may also influence adiponectin regulation independently, a finding that should be confirmed in longitudinal studies.

Topics: Adiponectin; Adult; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Clozapine; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Glucose Tolerance Test; Humans; Male; Metabolic Syndrome; Olanzapine; Psychotic Disorders; Risk Factors; Schizophrenia

To investigate 3-month changes in glucose metabolism in a naturalistic sample of patients with schizophrenia newly started on or switched to specific atypical antipsychotic medication therapy.. One hundred eighty-three patients were evaluated before initiation and 3 months after with a 75-g glucose load oral glucose tolerance test (OGTT). Data were collected between November 2003 and January 2007.. Eight patients (4.4%) developed new-onset diabetes within 3 months. Initiation of clozapine resulted in a significantly higher risk for new-onset glucose abnormalities than initiation of aripiprazole (odds ratio = 67.29, 95% CI = 5.23 to 866.49). Significant drug x time interactions were found for all OGTT glucose assessments (fasting: F = 6.79, df = 5,177; p < .0001; 30 minutes: F = 3.89, df = 5,177; p = .0023; 60 minutes: F = 5.03, df = 5,177; p = .0002; 120 minutes: F = 3.78, df = 5,177; p = .0028), with the evolution of plasma glucose levels being significantly worse in patients initiated on clozapine therapy (fasting, 30 minutes, and 60 minutes), olanzapine therapy (fasting, 60 minutes, and 120 minutes), and quetiapine therapy (fasting and 60 minutes) than in patients initiated on aripiprazole therapy (p < .05). Clozapine was also significantly more deleterious than risperidone and amisulpride for fasting plasma glucose level changes (p < .05). Type of initiation (start or switch) did not affect any of the metabolic parameters.. The incidence of new-onset glucose abnormalities, including diabetes, in the first 3 months after newly starting or switching atypical antipsychotic medication is high and may be markedly influenced by type of prescribed antipsychotic. The importance of accurately screening for new-onset glucose abnormalities after initiation of an atypical antipsychotic is emphasized.

Topics: Adult; Aged; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Blood Glucose; Body Mass Index; Clozapine; Diabetes Mellitus, Type 2; Dibenzothiazepines; Fasting; Feeding Behavior; Female; Glucose; Glucose Tolerance Test; Humans; Incidence; Insulin; Male; Middle Aged; Olanzapine; Piperazines; Prevalence; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risk Factors; Schizophrenia; Time Factors

Intraportal infusion of serotonin (5-hydroxytryptamine, 5-HT) or inhibitors of its cellular uptake stimulate hepatic glucose uptake in vivo by either direct or indirect mechanisms. The aims of this study were to determine the direct effects of 5-HT in hepatocytes and to test the hypothesis that atypical antipsychotic drugs that predispose to type 2 diabetes counter-regulate the effects of 5-HT.. Rat hepatocytes were studied in short-term primary culture.. Serotonin (5-HT) stimulated glycogen synthesis at nanomolar concentrations but inhibited it at micromolar concentrations. The stimulatory effect was mimicked by alpha-methyl-5-HT, a mixed 5-HT1/5-HT2 receptor agonist, whereas the inhibition was counteracted by a 5-HT2B/2C receptor antagonist. alpha-Methyl-5-HT stimulated glycogen synthesis additively with insulin, but unlike insulin, did not stimulate glucose phosphorylation and glycolysis, nor did it cause Akt (protein kinase B) phosphorylation. Stimulation of glycogen synthesis by alpha-methyl-5-HT correlated with depletion of phosphorylase a. This effect could not be explained by elevated levels of glucose 6-phosphate, which causes inactivation of phosphorylase, but was explained, at least in part, by decreased phosphorylase kinase activity in situ. The antipsychotic drugs clozapine and olanzapine, which bind to 5-HT receptors, counteracted the effect of alpha-methyl-5-HT on phosphorylase inactivation.. This study provides evidence for both stimulation and inhibition of glycogen synthesis in hepatocytes by serotonergic mechanisms. The former effects are associated with the inactivation of phosphorylase and are counteracted by atypical antipsychotic drugs that cause hepatic insulin resistance. Antagonism of hepatic serotonergic mechanisms may be a component of the hepatic dysregulation caused by antipsychotic drugs that predispose to type 2 diabetes.

Topics: Amides; Animals; Antipsychotic Agents; Benzodiazepines; Blotting, Western; Cells, Cultured; Clozapine; Diabetes Mellitus, Type 2; Enzyme Activation; Glycogen; Hepatocytes; Immunoblotting; Indoles; Male; Olanzapine; Phosphorylases; Rats; Rats, Wistar; Serotonin; Serotonin 5-HT1 Receptor Agonists; Serotonin 5-HT2 Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists

We report a patient with schizophrenia who developed diabetes mellitus during treatment with olanzapine. The case confirms the pattern of atypical antipsychotic-related diabetic emergencies: rapid onset in relatively young patients, often with severe glucose derangements and serious complications. As diabetic emergencies have a high morbidity and mortality, regular glucose screening should be performed in patients with schizophrenia treated with atypical antipsychotics.

Topics: Antipsychotic Agents; Benzodiazepines; Black People; Diabetes Mellitus, Type 2; Humans; Male; Middle Aged; Netherlands; Olanzapine; Schizophrenia, Paranoid

Differences in the glucose metabolism were examined and analysed in this study between patients treated with olanzapine and risperidone in comparison with healthy volunteers. The aim of the study was to determine differences of the impaired glucose metabolism in the study groups as well as to point out to the possible mechanisms which bring to these differences. To the group of 15 schizophrenic patients treated with olanzapine, and group of 15 schizophrenic patients treated with risperidone and to 14 healthy volunteers oral glucose tolerancy test is applied in order to determine the level of the impaired glucose tolerance. In the group of the patients treated with olanzapine glucose tolerance was impaired in 33% of the patients, while in the group of the patients treated with risperidone in 20%. Impaired glucose tolerance mostly manifested as hyperinsulinemia. Authors discussed about possible mechanisms responsible for the impaired glucose tolerance in the patients treated with new antipsychotics. Authors conclude that insulin resistance is the main mechanism for development of the diabetes type II in the schizophrenic patients treated with antipsychotics. Insulin resistance is the result of the multiple effects of the antipsychotics, among which most common are: increased body mass and direct involvement of the antipsychotics in the glucose metabolism.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Diabetes Mellitus, Type 2; Female; Glucose; Humans; Insulin Resistance; Male; Middle Aged; Olanzapine; Risperidone; Schizophrenia

The objective of this study was to evaluate the association of established risk factors for treatment-emergent diabetes (TED) among patients over 65 years of age with dementia who received treatment with olanzapine.. This was a post hoc analysis of data pooled from seven olanzapine clinical trials, which included patients over 65 years of age with dementia. The association of established risk factors for TED was evaluated using categorical and time-to-event analysis. TED was defined as two casual (fasting or nonfasting) glucose values > or =200 mg/dL at any time after baseline or one casual glucose value > or =200 mg/dL at the final visit, initiation of antidiabetic medication, or new clinical diagnosis of diabetes.. Elderly patients subsequently identified with TED (N = 29, 2.1%) had similar baseline body mass indices (24 kg/m(2)) and were similar in age (82 versus 80 years) to those who did not have TED. Cox proportional hazards model identified only elevated casual glucose (> or =140 mg/dL) measure at baseline to be significantly associated with the development of TED (hazard ratio [HR] = 11.2, p <0.0001) in this elderly cohort. Other clinical risk factors, like body mass index > or =25 (HR = 0.86), 7% weight gain (HR = 2.26), and antipsychotic treatment (HR = 1.36) were not significant.. In elderly patients with dementia enrolled in olanzapine clinical trials, an elevated casual glucose (> or =140 mg/dL) at baseline was the only risk factor significantly associated with subsequent development of TED. Risk of diabetes in these studies was not significantly associated with antipsychotic treatment group assignment.

Topics: Aged; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Clinical Trials as Topic; Cohort Studies; Dementia; Diabetes Mellitus, Type 2; Female; Humans; Male; Olanzapine; Retrospective Studies; Risk Factors

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Diabetes Mellitus, Type 2; Disease Progression; Humans; Hyperglycemia; Hyperlipidemias; Male; Olanzapine; Risperidone; Schizophrenia, Paranoid

The following is a case report analysis intended to draw attention to the need for better care coordination by describing the observed relationship of olanzapine to metabolic changes manifested as uncontrolled diabetes mellitus and weight gain. A 47-year-old male with bipolar I disorder/hallucinations presented to the Veterans Affairs Medical Center (VAMC) with suicidal ideations. He was referred to the psychiatry service where he was treated with olanzapine. He was followed exclusively by the psychiatry service for more than a year. During that time,weight issues and diabetes status were not addressed. Upon presenting to the primary care service a year and a half later, the patient was taking 40 mg per day of olanzapine and had gained 62 pounds, a 30% increase in body weight; glycosylated hemoglobin (A1c) was 11.1%. The patient was enrolled in a weight-loss clinic, and his diabetes medications were adjusted.Subsequently, olanzapine was discontinued because of weight gain and uncontrolled diabetes. Blood sugar and A1c were finally stabilized one month after discontinuation of olanzapine (A1c,6.9%). The patient experienced a relapse in his bipolar disorder,and olanzapine was restarted at 20 to 40 mg per day. His blood sugar became uncontrolled, he gained 13 pounds, and his A1c increased to 9.4%.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Diabetes Mellitus, Type 2; Humans; Hyperglycemia; Hypoglycemic Agents; Male; Middle Aged; Olanzapine; Weight Gain

To evaluate risk of new-onset type 2 diabetes associated with use of selected antipsychotic agents, the authors conducted a new-user cohort study in a national sample of US Veterans Health Administration patients with schizophrenia (and no preexisting diabetes). The authors studied 15,767 patients who initiated use of olanzapine, risperidone, quetiapine, or haloperidol in 1999-2001 after at least 3 months with no antipsychotic prescriptions. Patients were followed for just over 1 year. New-onset diabetes was identified through diagnostic codes and prescriptions for diabetes medication. In Cox proportional hazards regression adjusting for potential confounders, with patients initiating haloperidol use designated the reference group, diabetes risk was increased equally with new use of olanzapine (hazard ratio (HR) = 1.64, 95% confidence interval (CI): 1.22, 2.19), risperidone (HR = 1.60, 95% CI: 1.19, 2.14), or quetiapine (HR = 1.67, 95% CI: 1.01, 2.76). Diabetes risks were higher in patients under age 50 years. When data were reanalyzed with prevalent-user cohorts and matched case-control designs, results were similar, with slightly less elevated risk estimates. Assuming that the observed associations are causal, approximately one third of new cases of diabetes may be attributed to use of olanzapine, risperidone, and quetiapine in patients taking these medications. Prescribers should be mindful of diabetes risks when treating patients with schizophrenia.

Topics: Antipsychotic Agents; Benzodiazepines; Case-Control Studies; Cohort Studies; Diabetes Mellitus, Type 2; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Olanzapine; Proportional Hazards Models; Quetiapine Fumarate; Regression Analysis; Risk Factors; Risperidone; Schizophrenia; United States; Veterans

While the incidence of new-onset diabetes mellitus may be increasing in patients with schizophrenia treated with certain atypical antipsychotic agents, it remains unclear whether atypical agents are directly affecting glucose metabolism or simply increasing known risk factors for diabetes.. To study the 2 drugs most clearly implicated (clozapine and olanzapine) and risperidone using a frequently sampled intravenous glucose tolerance test.. A cross-sectional design in stable, treated patients with schizophrenia evaluated using a frequently sampled intravenous glucose tolerance test and the Bergman minimal model analysis.. Subjects were recruited from an urban community mental health clinic and were studied at a general clinical research center. Patients Fifty subjects signed informed consent and 41 underwent the frequently sampled intravenous glucose tolerance test. Thirty-six nonobese subjects with schizophrenia or schizoaffective disorder, matched by body mass index and treated with either clozapine, olanzapine, or risperidone, were included in the analysis.. Fasting plasma glucose and fasting serum insulin levels, insulin sensitivity index, homeostasis model assessment of insulin resistance, and glucose effectiveness.. The mean +/- SD duration of treatment with the identified atypical antipsychotic agent was 68.3 +/- 28.9 months (clozapine), 29.5 +/- 17.5 months (olanzapine), and 40.9 +/- 33.7 (risperidone). Fasting serum insulin concentrations differed among groups (F(33) = 3.35; P = .047) (clozapine>olanzapine>risperidone) with significant differences between clozapine and risperidone (t(33) = 2.32; P = .03) and olanzapine and risperidone (t(33) = 2.15; P = .04). There was a significant difference in insulin sensitivity index among groups (F(33) = 10.66; P<.001) (clozapineolanzapine>risperidone) (clozapine vs risperidone, t(33) = 2.94; P = .006; olanzapine vs risperidone, t(33) = 2.42; P = .02). There was a significant difference among groups in glucose effectiveness (F(30) = 4.18; P = .02) (clozapine

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Mass Index; Body Weight; Clozapine; Diabetes Mellitus, Type 2; Female; Glucose Tolerance Test; Humans; Insulin Resistance; Male; Metabolic Syndrome; Obesity; Olanzapine; Risperidone; Schizophrenia

To examine the risk of developing type 2 diabetes mellitus among people with schizophrenia exposed to atypical antipsychotics (clozapine, olanzapine, quetiapine, risperidone) compared to those exposed to conventional antipsychotics.. A matched case-control design was used to examine California Medicaid beneficiaries. Cases developed diabetes subsequent to being diagnosed with schizophrenia (ICD-9295), were 18 years or older, and were exposed to at least one antipsychotic medication at some point during the 12 weeks preceding diabetes diagnosis. Diabetes was defined by diagnostic claim (ICD-9250) or prescription for antidiabetic agents. A total of 3663 cases were matched to 14 523 non-diabetic controls (people with schizophrenia matched on gender and age +/-5 years). All had to be continuously eligible for benefits during the 12-week period preceding diabetes onset in the case. Conditional logistic regression modeled the risk of exposure, controlling for age, ethnicity, and exposure to selected concomitant medications. Analyses were repeated with 24- and 52-week exposure windows.. Using a 12-week exposure window, olanzapine (OR = 1.36, 95%CI 1.20-1.53), clozapine (OR = 1.34, 95%CI 1.16-1.55), and combination atypical therapy (OR = 1.58, 95%CI 1.33-1.88), but not risperidone or quetiapine, were associated with increased odds of developing diabetes compared to conventional antipsychotics. Changing to a 24-week exposure window, the risks were: olanzapine (OR = 1.38, 95%CI 1.22-1.56), clozapine (OR = 1.32, 95%CI 1.14-1.53), or combinations (OR = 1.54, 95%CI 1.29-1.84). With a 52-week exposure window, the risks were: olanzapine (OR = 1.41, 95%CI 1.24-1.60), clozapine (OR = 1.41, 95%CI 1.21-1.65), combinations (OR = 1.58, 95%CI 1.31-1.90). Risk for olanzapine increased with dose. Hispanic, African American, and unknown ethnicity were significant risks for development of type 2 diabetes as was exposure to selected concomitant medications.. Exposure to olanzapine or clozapine is associated with a 34-41% increase in the developing of type 2 diabetes among California Medicaid recipients with schizophrenia. Prospective, randomized trials are needed to confirm these retrospective, observational findings.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; California; Case-Control Studies; Clozapine; Databases, Factual; Diabetes Mellitus, Type 2; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Incidence; Logistic Models; Male; Medicaid; Middle Aged; Odds Ratio; Olanzapine; Quetiapine Fumarate; Risk Assessment; Risperidone; Schizophrenia; Time Factors

Topics: Antipsychotic Agents; Benzodiazepines; Diabetes Mellitus, Type 2; Humans; Olanzapine; Receptor, Muscarinic M3; Schizophrenia; Weight Gain

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Diabetes Mellitus, Type 2; Female; Humans; Olanzapine; Risk Factors; Schizophrenia

Topics: Antipsychotic Agents; Benzodiazepines; Bias; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Male; Olanzapine; Prediabetic State; Proportional Hazards Models; Retrospective Studies; Risk; Risperidone; Schizophrenia

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Glucose Tolerance Test; Humans; Insulin; Male; Olanzapine

The introduction of new antipsychotics has resulted in the availability of drugs with improved safety and tolerability as well as proven efficacy compared to the older antipsychotics. New compounds might show new or different adverse effects that arise in the post-marketing phase when a greater number of patients are treated. One goal of the drug safety program in psychiatry AMSP ( Arzneimittelsicherheit in der Psychiatrie) is the detection and description of severe, new, or rare adverse drug reactions (ADRs). Between 1993 and 2000, 122,562 patients were monitored in 35 psychiatric institutions, 86,349 patients of which received antipsychotics. Hyperglycemia related to antipsychotics was observed in association with only two compounds so far: clozapine and olanzapine (clozapine 2 cases, olanzapine 7 cases). In 6 of 9 patients, weight gain preceded hyperglycemia. The relative frequency of these adverse drug related events was 0.013 % for clozapine and 0.075 % for olanzapine. The symptomatology included reversible hyperglycemia, worsening of existing diabetes, and new-onset diabetes. Control for glycemic dysregulation should be maintained in clinical practice with these drugs.

Topics: Adult; Adverse Drug Reaction Reporting Systems; Aged; Antipsychotic Agents; Benzodiazepines; Clozapine; Diabetes Mellitus, Type 2; Female; Humans; Hyperglycemia; Male; Middle Aged; Olanzapine; Outcome Assessment, Health Care; Product Surveillance, Postmarketing; Prospective Studies; Psychotic Disorders; Retrospective Studies; Risk Factors

Type 2 diabetes is an important comorbid medical condition associated with schizophrenia. The objective of this study was to compare glycosylated hemoglobin (HbA(1c)) levels of patients who had type 2 diabetes and schizophrenia with those of patients who had type 2 diabetes and major mood disorders and those who had type 2 diabetes but who did not have severe mental illness.. A sample of 300 patients with type 2 diabetes was recruited from community mental health centers in the greater Baltimore region and nearby primary care clinics. Of these, 100 had schizophrenia, 101 had a major mood disorder, and 99 had no identified severe mental illness. HbA(1c), the main outcome measure, was compared between the group with schizophrenia and the other two groups.. All three groups had HbA(1c) values above recommended levels. HbA(1c) levels were significantly lower among patients with schizophrenia than among patients who did not have severe mental illness but were not significantly different from those of patients who had major mood disorders. Patients for whom olanzapine was prescribed had higher HbA(1c) levels than those for whom other antipsychotic agents were prescribed.. All three groups of patients require improved diabetes treatment to achieve acceptable HbA(1c) levels. There may be previously unrecognized benefits for diabetes management among persons with severe mental illnesses who are receiving regular mental heath care, but these individuals may also have risk factors that can influence diabetes outcomes and HbA(1c) levels.

Topics: Benzodiazepines; Body Mass Index; Demography; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Male; Mental Disorders; Middle Aged; Olanzapine; Schizophrenia; Severity of Illness Index

The atypical antipsychotics have been recognized to induce diabetes mellitus and ketoacidosis in the adult psychiatric population. This report notes the onset of weight gain, diabetes, and apparent ketosis in a prepubertal boy diagnosed with bipolar disorder and treated with olanzapine. The hyperglycemia rapidly normalized after discontinuation of the olanzapine. Within 2 years, the diabetes recurred. In spite of the normalization of blood-glucose levels, urine ketone tests remained positive and were explained by the fact that patients taking valproic acid may have a false-positive urine test for ketones. Regular monitoring of glucose should be considered in children and adolescents who gain weight while treated with atypical antipsychotics.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Child; Diabetes Mellitus, Type 2; Humans; Male; Olanzapine; Recurrence

The increasing use of olanzapine for treating adolescent patients has brought with it greater awareness of the recognized side effects of this medication, especially weight gain. Of the reports of glucose dysregulation related to olanzapine therapy, only a few pertain to adolescents. We present five cases: two youths who consequently suffered from overt diabetes and three who responded with glucose dysregulation. According to the Naranjo probability scale, the relation of this phenomenon to olanzapine therapy is "probable." We consider the findings of the presented case series as justification for regular metabolic follow-up for apparently healthy adolescents receiving olanzapine therapy.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Diabetes Mellitus, Type 2; Female; Humans; Hyperglycemia; Male; Olanzapine; Pirenzepine; Psychotic Disorders; Weight Gain

Atypical antipsychotics are being used increasingly in the management of mood disorders.. The objective of this study was to investigate the association between exposure to antipsychotic therapy and newly reported type 2 diabetes mellitus in patients with mood disorders.. Claims data for the period January 1996 through December 1997 were analyzed for patients with mood disorders in 2 large US health plans. Logistic regression models were used to determine the odds of reporting diabetes in patients exposed to risperidone, olanzapine, or high- or low-potency conventional antipsychotics compared with untreated patients, taking into account duration of treatment and dosage. Some of the covariates used in the models were concurrent use of antipsychotics, use of other psychotropic drugs, age, sex, and length of observation.. Based on the claims data, 849 patients were exposed to risperidone, 656 to olanzapine, 785 to high-potency conventional antipsychotics, and 302 to low-potency conventional antipsychotics; 2644 patients were untreated. The odds of newly reported type 2 diabetes in patients who received risperidone were not significantly different from those in untreated patients (12-month odds ratio [OR] = 1.024; 95% CI, 0.351-3.015). The odds in patients treated with high-potency conventional antipsychotics also did not differ significantly from those of untreated patients (12-month OR = 1.945; 95% CI, 0.794-4.786). Unlike patients who received risperidone or high-potency conventional antipsychotics, patients who received olanzapine (12-month OR = 4.289; 95% CI, 2.102-8.827) and low-potency conventional antipsychotics (12-month OR = 4.972; 95% CI, 1.967-12.612) had significantly higher odds for the development of type 2 diabetes compared with untreated patients.. These findings suggest that some antipsychotics may increase the risk for the development of type 2 diabetes in patients with mood disorders and that the effect may vary by drug. In contrast to olanzapine and low-potency conventional antipsychotics, risperidone and high-potency conventional antipsychotics were not associated with an increased risk for development of type 2 diabetes in this patient population.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Data Collection; Diabetes Mellitus, Type 2; Female; Humans; Insurance Claim Review; Logistic Models; Male; Mood Disorders; Odds Ratio; Olanzapine; Pirenzepine; Risk Factors; Risperidone; United States

Recent results suggest that treatment with the atypical antipsychotics clozapine and olanzapine is associated with increased insulin and lipid levels.. The aim of the present study was to investigate potential relationships between insulin or other hormones related to glucose-insulin homeostasis or lipids and steady-state serum concentrations of clozapine or olanzapine in patients on therapeutic doses.. Thirty-four patients, diagnosed with schizophrenia or related psychoses according to the DSM-IV criteria and treated with clozapine ( n=18) or olanzapine ( n=16), were studied. Median treatment time with the antipsychotics was 5.3 years (range 0.5-16.3 years). Fasting blood samples for insulin, C-peptide, insulin-like growth factor I, insulin-like growth factor binding protein-1, leptin, glucose and lipids were analyzed and investigated in relation to the patients' drug serum concentrations.. Hyperinsulinemia was found in 30-60% of the patients, hyperglycemia in 10-30%, hyperlipidemia in 40-60% and hyperleptinemia in 10-20%. Moreover, levels of insulin, C-peptide and triglycerides correlated positively to the clozapine serum concentration and to the ratio of olanzapine to N-desmethylolanzapine concentrations. In contrast, levels of C-peptide, leptin and blood glucose were inversely correlated to the serum concentration of the metabolite N-desmethylolanzapine.. Metabolic abnormalities (i.e. hyperinsulinemia, hyperlipidemia and hyperleptinemia) and insulin resistance were associated with both clozapine and olanzapine treatments. Levels of insulin and triglycerides increased by increasing clozapine serum concentration and by increasing ratio of olanzapine to N-desmethylolanzapine; the last due to the metabolite N-desmethylolanzapine probably having an inverse effect to the main compound olanzapine. Thus, the metabolic abnormalities induced by these two drugs are clozapine-concentration dependent in clozapine-treated patients, and ratio of olanzapine to N-desmethylolanzapine-concentration dependent in olanzapine-treated patients.

Topics: Adult; Benzodiazepines; Blood Glucose; Body Mass Index; C-Peptide; Chromatography, High Pressure Liquid; Clozapine; Diabetes Mellitus, Type 2; Diagnostic and Statistical Manual of Mental Disorders; Dose-Response Relationship, Drug; Female; Hormones; Humans; Insulin; Lipids; Male; Middle Aged; Olanzapine; Radioimmunoassay; Schizophrenia; Smoking; Statistics as Topic; Triglycerides

Since a few years, an increasing number of cases of atypical neuroleptic-associated diabetes are reported in the literature. But few are dedicated to diabetologists. We report here two cases of patients with a severe deterioration of preexisting diabetes, with clozapine for the first case report and olanzapine for the second one. We also make a literature review and discuss the possible mechanisms involved in this atypical neuroleptic-associated diabetes. We recommend a thigh follow-up of weight, glycemic and lipidic parameters during psychotic patients treatment with atypical neuroleptics, in order to prevent or rapidly treat the metabolic complications described in the literature.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Clozapine; Diabetes Mellitus, Type 2; Disease Progression; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Risk

During the last few years there have been numerous publications concerning glucose dysregulation and antipsychotic treatment with new-onset diabetes and exacerbation of existing disease being reported. At the same time three anecdotal reports describing decrease of blood glucose level during clozapine and olanzapine treatment were published. Here we report two cases of clinically significant dose-related reductions in glucose levels in schizophrenic and schizoaffective patients suffering from pre-existing type 2 diabetes during high dose (40 mg/day) olanzapine treatment. To the best of our knowledge, this is a first report of decreasing glucose blood levels in association with olanzapine therapy in pre-existing type 2 diabetes. Antipsychotic treatment with high doses of olanzapine showed that the relationship between olanzapine and glucose regulation is more unambiguous than usually assumed.. There is a need for further studies in order to define the influence of high dose olanzapine for schizophrenic and schizoaffective patients suffering from type 2 diabetes.

Topics: Antipsychotic Agents; Benzodiazepines; Blood Glucose; Comorbidity; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Middle Aged; Olanzapine; Psychotic Disorders; Schizophrenia; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Diabetes Mellitus, Type 2; Humans; Hyperglycemia; Male; Olanzapine; Piperazines; Pirenzepine; Schizophrenia, Paranoid; Thiazoles; Treatment Outcome

The novel antipsychotics are extensively used based on their favorable extrapyramidal side effect profiles. However, accumulating evidence suggests that these agents, particularly clozapine and olanzapine, have serious side effects of their own, including weight gain and elevated glucose and triglyceride levels. The goal of this study is to compare the effects of novel antipsychotics clozapine, olanzapine, risperidone, and quetiapine and typical antipsychotics haloperidol and fluphenazine on glucose and lipid levels.. The charts of 590 patients were retrospectively reviewed. Of those, 215 patients had adequate laboratory data for inclusion. Glucose and lipid level data from 2 1/2 years before and after initiation of the target antipsychotic were included. Covariates, including patients' age, the duration of antipsychotic treatment, other medications that may affect glucose or lipid levels, and the initial laboratory values, were controlled for in the analyses.. Glucose levels were increased from baseline for patients treated with clozapine, olanzapine, and haloperidol. There were statistically and clinically significant differences among the medications' effects on lipid profiles (p < .05). Those receiving clozapine and olanzapine demonstrated statistically significant increases in triglyceride levels compared with the other groups. Over one third of patients treated with any of the novel antipsychotics had clinically meaningful triglyceride elevations.. It has been shown that novel antipsychotics are associated with weight gain. This risk factor along with others, such as elevated glucose and triglyceride levels, compounds the risk for coronary artery disease. Routine monitoring of glucose and lipid levels during treatment with novel antipsychotics should be advocated.

Topics: Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Mass Index; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Clozapine; Diabetes Mellitus, Type 2; Dibenzothiazepines; Female; Haloperidol; Humans; Hyperlipidemias; Lipids; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risk Factors; Risperidone; Triglycerides; Weight Gain

Case series suggest that some antipsychotics may induce or exacerbate type 2 diabetes. This study measured the association of antipsychotic treatments with diabetes at a population level.. Claims data for psychosis patients (ICD-CM-9 290.xx-299.xx) within health plans encompassing 2.5 million individuals were analyzed. Patients reporting preexisting type 2 diabetes up to 8 months prior to observation were excluded. The frequency of newly reported type 2 diabetes in untreated patients and among patients treated with antipsychotics from 5 categories (risperidone, olanzapine, clozapine, and high-potency and low-potency conventionals) was compared. Logistic regression models compared the odds of diabetes based on exposure to each of the antipsychotic categories.. Based on 12 months of exposure, the odds of type 2 diabetes for risperidone-treated patients (odds ratio = 0.88, 95% CI = 0.372 to 2.070) was not significantly different from that for untreated patients, whereas patients receiving other antipsychotics had a significantly greater risk of diabetes than untreated patients (p < .05): olanzapine, 3.10 (95% CI = 1.620 to 5.934); clozapine, 7.44 (95% CI = 0.603 to 34.751); high-potency conventionals, 2.13 (95% CI = 1.097 to 4.134); and low-potency conventionals, 3.46 (95% CI = 1.522 to 7.785). Older age and greater use of non-antipsychotic psychotropic medications also contributed to risk of type 2 diabetes. Olanzapine also showed significantly higher (p < .01) odds of diabetes associated with increasing dose.. Consistent with previously published literature, these data suggest that olanzapine, clozapine, and some conventional antipsychotics appear to increase the risk of acquiring or exacerbating type 2 diabetes and that the effect may vary by drug. In contrast to these agents, risperidone was not associated with an increased risk of type 2 diabetes.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Comorbidity; Confidence Intervals; Databases as Topic; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Insurance Claim Review; Logistic Models; Male; Middle Aged; Odds Ratio; Olanzapine; Pirenzepine; Psychotic Disorders; Risk Factors; Risperidone; United States

The development of both type I and type II diabetes after initiation of some atypical neuroleptics has been reported, primarily in studies involving small series of patients. This study used administrative data from a large national sample of patients with a diagnosis of schizophrenia to compare the prevalence of diabetes mellitus in patients receiving prescriptions for atypical and typical neuroleptics.. All outpatients with schizophrenia treated with typical and atypical neuroleptics over 4 months in 1999 in the Veterans Health Administration of the Department of Veterans Affairs (VA) were included in this study. Patients treated with atypical neuroleptics were those who received prescriptions for clozapine, olanzapine, risperidone, or quetiapine. Patients with a diagnosis of diabetes were also identified by using ICD-9 codes in VA administrative databases. The prevalence of diabetes mellitus across age groups and among patients receiving prescriptions for different atypical neuroleptics was examined with multiple logistic regression.. A total of 38,632 patients were included in the study: 15,984 (41.4%) received typical neuroleptics and 22,648 (58.6%) received any atypical neuroleptic (1,207 [5.3%] received clozapine; 10,970 [48.4%], olanzapine; 955 [4.2%], quetiapine; and 9,903 [43.7%], risperidone; 387 patients received prescriptions for more than one atypical neuroleptic). When the effects of age were controlled, patients who received atypical neuroleptics were 9% more likely to have diabetes than those who received typical neuroleptics, and the prevalence of diabetes was significantly increased for patients who received clozapine, olanzapine, and quetiapine, but not risperidone. However, for patients less than 40 years old, all of the atypical neuroleptics were associated with a significantly increased prevalence of diabetes.. In this large group of patients with schizophrenia, receipt of a prescription for atypical neuroleptics was significantly associated with diabetes mellitus.

Topics: Adult; Adverse Drug Reaction Reporting Systems; Aged; Antipsychotic Agents; Benzodiazepines; Clozapine; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Quetiapine Fumarate; Regression Analysis; Risk Factors; Risperidone; Schizophrenia

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Body Weight; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Male; Olanzapine; Pirenzepine

Topics: Antipsychotic Agents; Benzodiazepines; Blood Glucose; Diabetes Mellitus, Type 2; Female; Humans; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Risk Factors

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Black People; Blood Glucose; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Schizophrenia; White People

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Diabetes Mellitus, Type 2; Drug Administration Schedule; Humans; Male; Olanzapine; Patient Compliance; Pirenzepine; Quality of Life; Schizophrenia, Paranoid

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.

Topics: Benzodiazepines; Blood Glucose; Diabetes Mellitus, Type 2; Disease Progression; Humans; Hyperglycemia; Long-Term Care; Male; Mental Disorders; Middle Aged; Olanzapine; Pirenzepine; Selective Serotonin Reuptake Inhibitors

The new antipsychotics induce minimal extrapyramidal side effects, probably due to their relatively greater affinity for certain nondopaminergic receptors than their older, conventional counterparts; however, this polyreceptor affinity may be responsible for the development of other adverse effects. One serious adverse effect that may be linked to these effects is non-insulin-dependent diabetes mellitus.. We summarize 6 new cases of clozapine- and olanzapine-associated diabetes that we have documented in our clinic. We compare our cases to previous reports and tabulate the pertinent similarities among cases.. Two of the cases were olanzapine-associated and 4 were clozapine-associated diabetes. Five of our 6 patients had risk factors for diabetes, as have 7 of the 9 previously reported in the literature. Four of our 6 patients, and 2 of the 4 prior cases in which such data were reported, experienced substantial weight gain after starting their antipsychotics.. Novel antipsychotics should be administered with great care to patients with risk factors for diabetes. Although the precise mechanism of the novel antipsychotic-associated diabetes is unclear, we hypothesize that histaminic and possibly serotonergic antagonism induces weight gain, which in turn leads to changes in glucose homeostasis. Additionally, serotonin1A antagonism might decrease pancreatic beta-cell responsiveness, resulting in inappropriately low insulin and hyperglycemia.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Diabetes Mellitus, Type 2; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Risk Factors; Schizophrenia

Topics: Adult; Antidepressive Agents; Benzodiazepines; Clomipramine; Dehydration; Depressive Disorder; Diabetes Mellitus, Type 2; Female; Humans; Hyperglycemia; Olanzapine; Pirenzepine; Syndrome

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hyperglycemia; Male; Olanzapine; Pirenzepine; Psychotic Disorders; Recurrence