olanzapine and Hyperlipidemias

Atypical antipsychotic medications (second-generation antipsychotics) have been increasingly used in the treatment of a number of psychotic disorders since their introduction in 1988, with the newest medication introduced in 2002. Justification for their use includes claims of equal or improved antipsychotic activity over first-generation antipsychotics, increased tolerability, and decreased side effects. However, there are still significant adverse effects and toxicities with this class of medications. Toxicologic exposures and fatalities associated with atypical antipsychotics continue to increase in the United States, with 32,422 exposures and 72 deaths in 2003. There have also been Food and Drug Administration warnings in the past year about how some atypical antipsychotics have been marketed to minimize the potentially fatal risks and claiming superior safety to other atypical antipsychotics without adequate substantiation, indicating the toxicologic potential of these agents may be underestimated.. Continued research to evaluate adverse effects and tolerability of atypical antipsychotics compared with first-generation antipsychotics and each other is reviewed. This article also reviews the pharmacodynamics, pharmacokinetics, and drug interactions with these medications. New therapeutic monitoring recommendations for this class of medications have also been proposed. Finally, clinical toxicity in overdose and management are reviewed.. While new atypical antipsychotic medications may have a safer therapeutic and overdose profile than first-generation antipsychotic medications, many adverse and toxic effects still need to be considered in therapeutic monitoring and overdose management.

Topics: Antipsychotic Agents; Aripiprazole; Basal Ganglia Diseases; Benzodiazepines; Cardiomyopathies; Child; Clozapine; Diabetes Mellitus; Dibenzothiazepines; Drug Interactions; Drug Overdose; Dry Eye Syndromes; Humans; Hyperlipidemias; Hypotension; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Seizures; Thiazoles

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

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

Weight gain is a side effect of therapy with many atypical antipsychotics and may have important clinical repercussions with respect to long-term health and treatment compliance. The primary objective of this double-blind study was to compare the safety and tolerability of aripiprazole and olanzapine in patients with schizophrenia as evidenced by the percentage of patients exhibiting significant weight gain.. This was a 26-week, multicenter, randomized, double-blind, active-controlled trial in patients with DSM-IV schizophrenia who were in acute relapse and required hospitalization. Significant weight gain was defined as a > or = 7% increase in body weight from baseline. Body weight, Positive and Negative Syndrome Scale, and Clinical Global Impressions-Improvement scale (CGI-I) assessments were performed at baseline and at regular intervals during the study. The study period was from April 2000 through June 2001.. 317 patients were randomly assigned to aripiprazole (N = 156) or olanzapine (N = 161). Compared with those treated with aripiprazole, a greater proportion of patients treated with olanzapine exhibited clinically significant weight gain during the trial. By week 26, 37% of olanzapine-treated patients had experienced significant weight gain compared with 14% of aripiprazole-treated patients (p < .001). Statistically significant differences in mean weight change were observed between treatments beginning at week 1 and sustained throughout the study. At week 26, there was a mean weight loss of 1.37 kg (3.04 lb) with aripiprazole compared with a mean increase of 4.23 kg (9.40 lb) with olanzapine among patients who remained on therapy (p < .001). Changes in fasting plasma levels of total cholesterol, high-density lipoprotein cholesterol, and triglycerides were significantly different in the 2 treatment groups, with worsening of the lipid profile among patients treated with olanzapine. There was a consistent and sustained improvement in symptoms in patients who remained on therapy with either olanzapine or aripiprazole as assessed by CGI-I scores and responder rates throughout the study.. Olanzapine had a greater impact on patients' weight than aripiprazole. Significant differences in favor of aripiprazole were also observed in the effects of therapy on plasma lipid profile. Both treatment groups achieved comparable clinically meaningful improvements on efficacy measures. The observed effects on weight and lipids indicate a potentially lower metabolic and cardiovascular risk in patients treated with aripiprazole compared with those treated with olanzapine.

Topics: Acute Disease; Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Double-Blind Method; Female; Humans; Hyperlipidemias; Incidence; Lipids; Male; Obesity; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Quinolones; Schizophrenia; Schizophrenic Psychology; Secondary Prevention; Treatment Outcome; Weight Gain

Atypical antipsychotics, such as olanzapine, are commonly prescribed to patients with schizophrenic symptoms and other psychiatric disorders. However, weight gain and metabolic disturbance cause adverse effects, impair patient compliance and limit clinical utility. Thus, a better understanding of treatment-acquired adverse effects and identification of targets for therapeutic intervention are believed to offer more clinical benefits for patients with schizophrenia. Beyond its nutritional effects, studies have indicated that supplementation of chromium brings about beneficial outcomes against numerous metabolic disorders. In this study, we investigated whether olanzapine-induced weight gain and metabolic disturbance involved chromium dynamic mobilization in a female Sprague-Dawley rat model, and whether a dietary supplement of chromium improved olanzapine-acquired adverse effects. Olanzapine medicated rats experienced weight gain and adiposity, as well as the development of hyperglycemia, hyperinsulinemia, insulin resistance, hyperlipidemia, and inflammation. The olanzapine-induced metabolic disturbance was accompanied by a decrease in hepatic Akt and AMP-activated Protein Kinase (AMPK) actions, as well as an increase in serum interleukin-6 (IL-6), along with tissue chromium depletion. A daily intake of chromium supplements increased tissue chromium levels and thermogenic uncoupling protein-1 (UCP-1) expression in white adipose tissues, as well as improved both post-olanzapine weight gain and metabolic disturbance. Our findings suggest that olanzapine medicated rats showed a disturbance of tissue chromium homeostasis by inducing tissue depletion and urinary excretion. This loss may be an alternative mechanism responsible for olanzapine-induced weight gain and metabolic disturbance.

Topics: Adipose Tissue, White; Adiposity; Administration, Oral; AMP-Activated Protein Kinases; Animals; Antipsychotic Agents; Chlorides; Chromium Compounds; Female; Gene Expression Regulation; Hyperglycemia; Hyperinsulinism; Hyperlipidemias; Inflammation; Insulin Resistance; Interleukin-6; Liver; Muscle, Skeletal; Olanzapine; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Signal Transduction; Uncoupling Protein 1; Weight Gain

Olanzapine, an atypical antipsychotic drug, has therapeutic effects for schizophrenia. However, clinical reports indicate that patients taking atypical antipsychotic drugs are at high risk of metabolic syndrome with unclear mechanisms. We investigated the effect of olanzapine on atherosclerosis and the mechanisms in apolipoprotein E-null (apoE-/-) mice.. ApoE-/- mice were used as in vivo models. Western blot analysis was used to evaluate protein expression. Conventional assay kits were applied to assess the levels of cholesterol, triglycerides, free cholesterol, cholesteryl ester, fatty acids, glycerol, and cytokines.. Daily treatment with olanzapine (3 mg/kg body weight) for four weeks increased mean arterial blood pressure and the whitening of brown adipose tissue in mice. In addition, olanzapine impaired aortic cholesterol homeostasis and exacerbated hyperlipidemia and aortic inflammation, which accelerated atherosclerosis in mice. Moreover, lipid accumulation in liver, particularly total cholesterol, free cholesterol, fatty acids, and glycerol, was increased with olanzapine treatment in apoE-/- mice by upregulating the expression of de novo lipid synthesis-related proteins and downregulating that of cholesterol clearance- or very low-density lipoprotein secretion-related proteins.. Olanzapine may exacerbate atherosclerosis by deregulating hepatic lipid metabolism and worsening hyperlipidemia and aortic inflammation.

Topics: Adipose Tissue, White; Animals; Antipsychotic Agents; Aorta; Apolipoproteins E; Atherosclerosis; Benzodiazepines; Blood Pressure; Cholesterol; Fatty Acids; Hyperlipidemias; Inflammation; Lipid Metabolism; Liver; Male; Mice; Mice, Knockout; Olanzapine; Triglycerides

Although hyperlipidemia is a well known adverse event of atypical antipsychotic (AAP) medication, there are few studies that have quantitatively compared the risks of various AAPs.. Our aim was to comparatively evaluate the risk of hyperlipidemia associated with the use of AAPs approved in Japan through a consecutive epidemiological study.. We conducted a sequence symmetry analysis (SSA) using health insurance claims data to analyze the following nine AAPs approved for use in Japan: risperidone, paliperidone, perospirone hydrochloride hydrate, blonanserin, clozapine, olanzapine, quetiapine fumarate, aripiprazole, and zotepine. Exposed cases were identified from drug dispensing records as those who had been administered both AAPs and antihyperlipidemic drugs. The adjusted sequence ratio (ASR) and 95 % confidence interval (CI) for each individual AAP and for all AAPs were calculated while controlling for time trends in dispensing patterns.. Olanzapine was significantly associated with increased hyperlipidemia occurrence (ASR 1.56; 95 % CI 1.25-1.95). The ASRs obtained for risperidone (1.01; 95 % CI 0.80-1.27), perospirone hydrochloride hydrate (0.93; 95 % CI 0.63-1.39), blonanserin (0.83; 95 % CI 0.52-1.33), quetiapine fumarate (0.93; 95 % CI 0.73-1.18), and aripiprazole (1.02; 95 % CI 0.82-1.26) were approximately 1.0. Unstable estimates (wide CIs) were obtained for paliperidone and zotepine due to the small sample sizes.. Among the AAPs used in Japan, only olanzapine was found to have an elevated risk of hyperlipidemia. In contrast, risperidone, perospirone hydrochloride hydrate, blonanserin, quetiapine fumarate, and aripiprazole had relatively low risks.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Child; Child, Preschool; Databases, Factual; Female; Humans; Hyperlipidemias; Incidence; Infant; Infant, Newborn; Japan; Male; Middle Aged; Olanzapine; Patient Safety; Risk Assessment; Risk Factors; Time Factors; Young Adult

Patients with schizophrenia receive medication to alleviate various symptoms, but some efficacious second generation antipsychotics, particularly olanzapine, can cause obesity, dyslipidemia, and diabetes mellitus. It has been generally considered that olanzapine contributes to the development of diabetes by inducing obesity and subsequent insulin resistance. In this study, we examined the effect of olanzapine and risperidone, another second generation antipsychotic, on a hamster pancreatic β cell line, and found that both evoked mild endoplasmic reticulum (ER) stress, as evidenced by mild activation of the ER stress sensor molecule PERK. Surprisingly, only olanzapine induced marked apoptosis. Phosphorylation of the α subunit of eukaryotic initiation factor 2, an event immediately downstream of PERK activation, was not observed in cells treated with olanzapine, protein synthesis continued despite PERK activation, and ER stress was thereby sustained. Secretion of insulin was markedly inhibited, and both proinsulin and insulin accumulated inside olanzapine-treated cells. Inhibition of protein synthesis and knockdown of insulin mRNA, which result in less unfolded protein burden, both attenuated subsequent olanzapine-induced apoptosis. Given clinical observations that some patients taking olanzapine exhibit hyperlipidemia and hyperglycemia without gaining weight, our observations suggest that damage to pancreatic β cells may contribute to the undesirable metabolic consequences of olanzapine treatment in some cases.

Topics: Animals; Antipsychotic Agents; Apoptosis; Benzodiazepines; Cell Line; Cricetinae; Diabetes Mellitus; eIF-2 Kinase; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Eukaryotic Initiation Factor-2; HEK293 Cells; Hep G2 Cells; Humans; Hyperglycemia; Hyperlipidemias; Insulin; Insulin Secretion; Insulin-Secreting Cells; Mice; Olanzapine; Phosphorylation; Proinsulin; Protein Biosynthesis; Risperidone; RNA, Messenger; Schizophrenia; Unfolded Protein Response

Prior investigations suggest that olanzapine use declined rapidly after a U.S. Food and Drug Administration (FDA) communication and consensus statement warning of the drug's increased metabolic risks, but whether declines differed by racial-ethnic groups is unknown.. Changes in olanzapine use over time by race-ethnicity was assessed among 7,901 Florida Medicaid enrollees with schizophrenia.. Prior to the advisory, 57% of second-generation antipsychotic fills among Hispanics were for olanzapine, compared with 40% for whites or blacks (adjusted risk difference [ARD]=.17, 95% confidence interval [CI]=.13-.20). Olanzapine use declined among all racial-ethnic groups. Although Hispanics had greater olanzapine use than whites in each period, the differences in absolute risk were only 3% by the latest study period (ARD=.03, CI=.01-.04).. After the FDA communication and consensus statement were issued, differences in olanzapine use between white and Hispanic enrollees narrowed considerably. Identifying high-use subgroups for targeted delivery of drug safety information may help eliminate any existing differences in prescribing.

Topics: Antipsychotic Agents; Benzodiazepines; Black People; Confidence Intervals; Diabetes Mellitus; Florida; Hispanic or Latino; Humans; Hyperlipidemias; Medicaid; Olanzapine; Racial Groups; Schizophrenia; United States; United States Food and Drug Administration; White People

The goal of this study was to select some genes that may serve as good candidates for future studies of the direct effects (not explained by obesity) of some antipsychotics on hyperlipidemia. A search for single-nucleotide polymorphisms (SNPs) that may be associated with these direct effects was conducted. From a published cross-sectional sample, 357 patients on antipsychotics were genotyped using a DNA microarray with 384 SNPs. A total of 165 patients were taking olanzapine, quetiapine or chlorpromazine which may directly cause hypertriglyceridemia or hypercholesterolemia. Another 192 patients taking other antipsychotics were controls. A two-stage statistical analysis that included loglinear and logistic models was developed to select SNPs blindly. In a third stage, physiological knowledge was used to select promising SNPs. Known physiological mechanisms were supported for 3 associations found in patients taking olanzapine, quetiapine or chlorpromazine [acetyl-coenzyme A carboxylase alpha SNP (rs4072032) in the hypertriglyceridemia model, and for the neuropeptide Y (rs1468271) and ACCbeta, (rs2241220) in the hypercholesterolemia model]. These genes may be promising candidates for studies of the direct effects of some antipsychotics on hyperlipidemia.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Chlorpromazine; Cross-Sectional Studies; Dibenzothiazepines; Female; Gene Frequency; Genetic Variation; Genotype; Humans; Hypercholesterolemia; Hyperlipidemias; Hypertriglyceridemia; Lipids; Male; Olanzapine; Oligonucleotide Array Sequence Analysis; Pharmacogenetics; Polymorphism, Single Nucleotide; Psychotic Disorders; Quetiapine Fumarate; Randomized Controlled Trials as Topic

Topics: Antipsychotic Agents; Benzodiazepines; Case-Control Studies; Confounding Factors, Epidemiologic; Humans; Hyperlipidemias; Olanzapine; Randomized Controlled Trials as Topic; Risk Factors; Treatment Outcome

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Humans; Hyperlipidemias; Male; Middle Aged; Olanzapine; Quetiapine Fumarate

Metabolic syndrome is a strong determinant of new-onset diabetes and coronary heart disease in general populations. Given the higher prevalence of metabolic syndrome among mentally ill patients, the syndrome poses a greater health risk to this population. Atypical antipsychotic treatment may exacerbate this condition. We compared both the rate and incidence of metabolic syndrome among schizophrenia patients (DSM-IV criteria) treated with the atypical antipsychotics aripiprazole or olanzapine or placebo from 4 double-blind, randomized, controlled clinical trials.. Metabolic syndrome was defined according to the Third Adult Treatment Panel (ATP III) Guidelines as the presence on follow-up of 3 of the following abnormalities: waist circumference > 102 cm if male and > 88 cm if female, high density lipoprotein (HDL) < 40 mg/dL if male and < 50 mg/dL if female, diastolic blood pressure >or= 85 mm Hg or systolic blood pressure >or= 130 mm Hg, fasting triglycerides >or= 150 mg/dL, fasting plasma glucose >or= 110 mg/dL. Both the rate of metabolic syndrome and the person-time incidence were computed from the on-treatment follow-up.. In the placebo-controlled trials, the rate of metabolic syndrome was 25.8% among 155 placebo patients and 19.9% for 267 aripiprazole patients (p = .466 by stratified log rank). The incidence of metabolic syndrome was 14.3% for 91 placebo patients versus 5.3% for 151 aripiprazole patients (p < .001). In the active comparator trials, patients treated with olanzapine (N = 373) versus aripiprazole (N = 380) exhibited rates of 41.6% and 27.9%, respectively (p = .0002). Incidence rates were 27.4% for 212 olanzapine patients versus 15.7% for 198 aripiprazole patients (p = .0055).. Both the rate and incidence of clinically relevant metabolic syndrome differ according to the choice of antipsychotic agent. The association between metabolic syndrome and treatment warrants careful consideration in the choice of antipsychotic agents.

Topics: Acute Disease; Adult; Anthropometry; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Cholesterol, HDL; Drug Administration Schedule; Female; Humans; Hyperlipidemias; Hypertension; Incidence; Male; Metabolic Syndrome; Olanzapine; Piperazines; Prevalence; Quinolones; Schizophrenia

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

Atypical antipsychotics have been related with hyperglycaemia, diabetes mellitus, weight gain and lipid alterations in some patients. This study analyzed whether continuous treatment with risperidone, olanzapine, or clozapine entails a risk of glucose or lipid metabolism alterations in schizophrenic patients.. Patients included in this study were schizophrenics who had received mono-therapeutic with clozapine, olanzapine or risperidone for a period of 1 to 3 years. Those schizophrenic patients who were diagnosed as diabetic during psychiatric treatment and those who showed fasting glycemia greater than or equal to 126 mg/dl in two consecutive measurements were considered cases. The remaining schizophrenic patients who were receiving treatment and did not show these alterations were considered controls.. In the adjusted analysis (multivariate logistic regression) of the effect of antipsychotic treatment on the presence of diabetes, which also assessed age and body-mass index, the adjusted odds ratio (OR) for olanzapine relative to risperidone was 2.22 (95% confidence interval [CI], 1.12-4.22), (p = 0.0228); and that for clozapine relative to risperidone was 2.87 (95% CI, 1.19, 6.93), (p = 0.0192). Both results reveal a significantly greater risk for the appearance of diabetes mellitus in patients treated with olanzapine or clozapine than in those treated with risperidone. There were significant differences in the risk of increase in triglycerides in patients receiving olanzapine (OR = 1.34; p = 0.0075) and clozapine (OR = 1.58; p = 0.0028).. The risk of the appearance of diabetes mellitus in patients treated with olanzapine is twice as high as that in patients treated with risperidone, and the risk in patients treated with clozapine is nearly triple as high as that found in patients treated with risperidone. Risperidone appears to be a safer antipsychotic drug in the long term, with regard to the risk of alterations in glucose and lipid metabolism.

Topics: Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Case-Control Studies; Clozapine; Diabetes Mellitus; Female; Humans; Hyperglycemia; Hyperlipidemias; Male; Middle Aged; Olanzapine; Risk Factors; Risperidone; Schizophrenia

This study aimed to examine the impact of ziprasidone and olanzapine on QTc interval, weight and metabolic parameters in adults with schizophrenia and other psychoses. A retrospective cohort chart review was performed of 191 randomly selected patients who were being treated with ziprasidone or olanzapine in an integrated health care system. Significant differences on QTc interval were not observed. A significant weight gain was observed in olanzapine-treated patients (P<0.001) but not in the ziprasidone-treated cohort (P>0.05). Furthermore, adverse metabolic changes associated with olanzapine administration were significant with respect to effects on total cholesterol (P=0.01), triglycerides (P=0.05) and haemoglobin A1C (HbA1C) (P<0.05), whereas significant favourable metabolic effects were observed in ziprasidone-treated patients with regard to total cholesterol (P<0.05), low-density lipoprotein (LDL) (P<0.01), high-density lipoprotein (HDL) (P<0.05) and HbA1c (P<0.05). Our results suggest that these two atypical antipsychotics are safe and well tolerated from a cardiovascular standpoint, with no differences in QTc interval prolongation being observed. Olanzapine-treated patients exhibited significant weight increases, whereas ziprasidone-treated patients exhibited weight loss. Olanzapine treatment was also associated with significant adverse effect on patient's lipid profile and HbA1c. These adverse metabolic effects were not observed in ziprasidone-treated patients although favourable effects were observed with regard to effect on total cholesterol, LDL, HDL and HbA1c.

Topics: Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Weight; Cholesterol, HDL; Cholesterol, LDL; Electrocardiography; Female; Glycated Hemoglobin; Heart Rate; Humans; Hyperlipidemias; Lipids; Male; Middle Aged; Olanzapine; Piperazines; Retrospective Studies; Schizophrenia; Thiazoles; Triglycerides

To compare the incidence rates of diabetes mellitus and dyslipidemia in ambulatory first-time users of risperidone and olanzapine.. The database for the Prescription Drug Insurance Plan in the province of Quebec was used as the data source for a population-based cohort study. Denominalized data were extracted for all ambulatory patients who first received an atypical antipsychotic between 1 January 1997 and 31 August 1999. Eligible patients were categorized as taking: no antidiabetic medication; no lipid reducing medication; neither type of medication. Those who started to use an outcome drug (an antidiabetic or lipid-lowering medication) before the end of the follow-up period (31 August 2000) were considered to have developed the corresponding outcome disease. Incidence rate ratios (IRR) (and 95% confidence intervals) for initiating antihyperglycemic or lipid-lowering drug treatment, or both were calculated. Outcomes on risperidone were compared to those on olanzapine.. A total of 19 582 eligible patients were included in the analysis. Relative to risperidone, olanzapine was associated with a higher risk of initiating a pharmacologic treatment for diabetes [IRR: 1.33 (1.03-1.74)], dyslipidemia [IRR: 1.49 (1.22-1.83)], or either condition [1.47 (1.23-1.76)].. Olanzapine seems to be associated with a higher risk of developing diabetes and/or dyslipidemia than risperidone. Further prospective studies are needed to rigorously assess the safety of olanzapine.

Topics: Adolescent; Adult; Ambulatory Care; Antipsychotic Agents; Benzodiazepines; Cohort Studies; Databases, Factual; Diabetes Mellitus; Drug Utilization; Female; Humans; Hyperlipidemias; Incidence; Insurance, Pharmaceutical Services; Male; Middle Aged; Olanzapine; Quebec; Risk Assessment; Risk Factors; Risperidone; Survival Analysis

Topics: Adult; Benzodiazepines; Body Mass Index; Cholesterol, HDL; Cholesterol, LDL; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Hyperlipidemias; Male; Olanzapine; Prospective Studies; Psychotic Disorders; Weight Gain

Atypical antipsychotics, especially clozapine and olanzapine, have been increasingly associated with weight gain and other adverse metabolic events (diabetes mellitus, hyperlipidemia) in non-mentally retarded populations. This report explores the incidence of this phenomenon in an institution-dwelling population of individuals with developmental disabilities.. A retrospective longitudinal analysis was performed for a sample of 41 adults with developmental disabilities and comorbid psychiatric and/or behavioral syndromes for whom treatment was converted from typical antipsychotics to olanzapine or risperidone for a minimum period of 2 years. Data were collected from October 1998 to September 2002. Among parameters analyzed were chlorpromazine equivalent dosage of antipsychotic, metabolic parameters, body mass index (BMI), level of concurrent medications, and concomitant dietary restrictions.. Thirty-two study subjects (78.0%) were men. The mean age of the study subjects was 43.6 years (at the end of the study). Thirty-seven (90.2%) had severe-to-profound mental retardation. Eight (19.5%) were on a restricted diet. Twenty-three subjects (56.1%) were switched from a typical antipsychotic to olanzapine, and 18 subjects (43.9%) were switched from a typical antipsychotic to risperidone. Of the subsample of subjects who were switched from a typical antipsychotic to risperidone, 12 (66.7%) went on to be switched to olanzapine because of either emergent side effects or lack of efficacy. For the overall sample (N = 41), there was a 19.3% increase in chlorpromazine-equivalent antipsychotic dosage from baseline to the 2-year endpoint along with a 5.6% decrease in fasting blood glucose from baseline to the 2-year endpoint. There were no significant differences between baseline and endpoint values for BMI, total cholesterol, low-density lipoprotein cholesterol, or triglycerides.. The findings of this 2-year evaluation suggest that clinically or statistically significant BMI increases as well as blood glucose and lipid elevations are not unavoidably correlated with the use of the atypical antipsychotic agents olanzapine and risperi-done and may be minimized by careful monitoring, a regimen of dietary control, and a moderate activity level in a residential population of individuals with mental retardation.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Mass Index; Cholesterol; Comorbidity; Diabetes Mellitus; Female; Humans; Hyperlipidemias; Intellectual Disability; Longitudinal Studies; Male; Metabolic Syndrome; Middle Aged; Motor Activity; Olanzapine; Psychotic Disorders; Retrospective Studies; Risperidone

The purpose of this research project was to investigate potential matrix effects of anticoagulant and lipemia on the response of olanzapine, desmethyl olanzapine, olanzapine-D(3) and desmethyl olanzapine-D(8) in an LC/MS/MS assay. Blank human serum and sodium heparin, sodium citrate, and K(3)EDTA plasma with various degrees of lipemia were fortified with olanzapine, desmethyl olanzapine, olanzapine-D(3) and desmethyl olanzapine-D(8). Six replicates of each sample were extracted using Waters Oasis MCX cartridges and analyzed using electrospray LC/MS/MS. The analytes were separated on a Phenomenex LUNA phenyl hexyl, 2 mm x 50 mm, 5 microm, analytical column and a gradient rising from 2 to 85% mobile phase B. Mobile phase A consisted of acetonitrile-ammonium acetate (20 mM) (52:48 v/v) and mobile phase B was formic acid-acetonitrile (0.1:100 v/v). Ion suppression was investigated through post column infusion experiments. The degree of lipemia of each sample, indicated by turbidity, was ranked into categories from least to greatest and used for statistical analyses. The results from analysis of variance testing indicated that lipemia, anticoagulant and their interaction significantly influenced mass spectral matrix effects and extraction matrix effects. Differential behavior between the analytes and labeled internal standards contributed to variability. The most significant source of variability however, was ion suppression due to co-eluting matrix components.

Topics: Anticoagulants; Benzodiazepines; Calibration; Chromatography, Liquid; Citrates; Edetic Acid; Heparin; Humans; Hyperlipidemias; Mass Spectrometry; Olanzapine; Pirenzepine; Reproducibility of Results; Sensitivity and Specificity; Sodium Citrate

Topics: Antipsychotic Agents; Benzodiazepines; Cholesterol; Clozapine; Humans; Hyperglycemia; Hyperlipidemias; Olanzapine; Pirenzepine; Schizophrenia; Triglycerides

Since their introduction to the US market, atypical antipsychotic drugs, such as olanzapine, have been widely prescribed for the management of psychosis and have increasingly been used in dermatologic settings for the treatment of psychogenic dermatoses. Mild hyperglycemia and hypertriglyceridemia have been documented from the use of these medications, but the range of effects on metabolism and the effects on skin are poorly characterized. OBSERVETION: We describe 3 patients who developed eruptive xanthomas, 1 of whom had relative insulin insufficiency, after starting olanzapine therapy. These cases further support the association of severe dyslipidemia with olanzapine use in selected patients.. With the increasing use of atypical antipsychotic agents in the dermatologic setting, the dyslipidemia that develops in association with olanzapine use emphasizes the need for periodic metabolic studies in high-risk patients.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Female; Humans; Hyperlipidemias; Male; Middle Aged; Olanzapine; Pirenzepine; Schizophrenia; Skin Diseases; Xanthomatosis

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

The newer antipsychotic agents exhibit a superior safety profile compared with conventional antipsychotic agents in terms of extrapyramidal symptoms. Previous studies have suggested an association between olanzapine treatment and hyperlipidemia. We evaluated this association using a large health care database.. The study was derived from the England and Wales-based General Practice Research Database, composed of 3.5 million subjects followed up between June 1, 1987, and September 24, 2000. A total of 18 309 individuals diagnosed as having schizophrenia were identified. A 6:1 matched nested case-control design was used. Conditional logistic regression was used to derive adjusted odds ratios (ORs), controlling for sex, age, and other medications and disease conditions influencing lipid levels. Antipsychotic drug exposure was defined as the receipt of at least 1 prescription for an antipsychotic medication within the 3 months before the date of diagnosis of hyperlipidemia.. There were 1268 incident cases of hyperlipidemia in the cohort, matched to 7598 control subjects. Olanzapine use was associated with nearly a 5-fold increase in the odds of developing hyperlipidemia compared with no antipsychotic exposure (OR, 4.65; 95% confidence interval [CI], 2.44-8.85) (P<.001) and more than a 3-fold increase compared with those receiving conventional agents (OR, 3.36; 95% CI, 1.77-6.39) (P<.001). Risperidone was not associated with increased odds of hyperlipidemia compared with no antipsychotic exposure (OR, 1.12; 95% CI, 0.60-2.11) (P =.72) or conventional antipsychotic exposure (OR, 0.81; 95% CI, 0.44-1.52) (P =.52).. We observed a strong association between olanzapine exposure and hyperlipidemia in schizophrenic patients. The possible metabolic consequences of olanzapine use should be given serious consideration by treating physicians.

Topics: Adult; Adverse Drug Reaction Reporting Systems; Aged; Antipsychotic Agents; Benzodiazepines; Case-Control Studies; England; Female; Humans; Hyperlipidemias; Male; Middle Aged; Odds Ratio; Olanzapine; Pirenzepine; Product Surveillance, Postmarketing; Risperidone; Schizophrenia; Schizophrenic Psychology; Wales

Metabolic side effects have been increasingly noted during therapy with novel antipsychotics, but there is a dearth of comprehensive comparative data in this area. The goal of this retrospective study was to examine the changes in weight parameters, fasting glucose, and fasting lipids in long-term inpatients treated with either risperidone or olanzapine.. A retrospective study was performed by reviewing charts of patients at Oregon State Hospital, Salem, who were treated during July and August 1999, comparing metabolic outcomes during the first year of therapy with either risperidone or olanzapine. Data were analyzed also by age, sex, and concurrent use of lithium or valproate. Included for analysis were patients at least 18 years old with baseline weights obtained within 3 weeks of drug initiation, and baseline fasting triglycerides, cholesterol, and glucose obtained within 3 months prior to drug initiation and at 1 year of treatment (+/- 4 weeks). The patients meeting these criteria in each drug cohort (risperidone, N = 47; olanzapine, N = 47) included 1 patient with diagnosed diabetes mellitus prior to onset of treatment.. Among those patients under 60 years old, olanzapine patients (N = 37) experienced significantly greater increases at 1 year in all metabolic parameters than the risperidone group (N = 39), except for weight variables: triglycerides +104.8 mg/dL (olanzapine) versus +31.7 mg/dL (risperidone) (p = .037); cholesterol +30.7 mg/dL (olanzapine) versus +7.2 mg/dL (risperidone) (p = .004); glucose +10.8 mg/dL (olanzapine) versus +0.74 mg/dL (risperidone) (p = .030). Patients under 60 years of age with concurrent use of lithium or valproate were associated with greater weight gain in both drug groups, but this difference was statistically significant only for the olanzapine cohort. Neither weight change nor use of lithium or valproate was associated with increases in glucose or lipids among those under 60 years old for either drug.. Olanzapine therapy is associated with significantly greater increases in fasting glucose and lipid levels for nongeriatric adult patients than risperidone, and the increases are not correlated with changes in weight parameters. Appropriate monitoring of fasting glucose and serum lipid levels should be considered during extended treatment with atypical antipsychotics.

Topics: Adult; Aged; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Weight; Diabetes Mellitus; Drug Therapy, Combination; Fasting; Female; Glucose Tolerance Test; Hospitalization; Humans; Hyperlipidemias; Lipid Metabolism; Lipids; Lithium; Male; Middle Aged; Olanzapine; Outcome Assessment, Health Care; Pirenzepine; Retrospective Studies; Risperidone; Schizophrenia; Valproic Acid

Newer atypical antipsychotics demonstrate superior effectiveness, with a diminished incidence of extrapyramidal side effects compared with older typical antipsychotics, but they have been associated with the development of obesity and new-onset diabetes. A small number of reports documenting modest hypertriglyceridemia related to newer antipsychotics have implicated fluperlapine, clozapine, and, most recently, olanzapine. This study summarizes the results of 14 cases of severe hypertriglyceridemia (>600 mg/dL) associated with olanzapine and quetiapine therapy occurring among inpatients at Oregon State Hospital, including 7 patients whose serum triglyceride levels exceeded 1,000 mg/ dL. Four of these patients also developed new-onset diabetes. Nine cases occurred during the first 8 months of treatment, with three cases identified within 3 months of commencing olanzapine or quetiapine therapy. Weight gain in olanzapine and quetiapine groups was modest (12.3 lb and 8.5 lb, respectively) and did not correlate with the severity of hypertriglyceridemia. Biochemical causes for severe hypertriglyceridemia associated with novel antipsychotics are unclear, but clinical monitoring of serum lipids must be added to the concerns about the metabolic consequences of therapy with certain newer antipsychotic agents.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Female; Humans; Hyperlipidemias; Hypertriglyceridemia; Lipids; Male; Olanzapine; Pirenzepine; Quetiapine Fumarate; Retrospective Studies