olanzapine and Hypertriglyceridemia

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

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

A recent 12-week controlled comparison demonstrated the superiority of clozapine to "high-dose" olanzapine in adolescents with treatment-refractory schizophrenia. In the present study, the authors conducted a 12-week, open-label, follow-up study to examine changes in lipid and glucose metabolism in youths maintained on clozapine and to determine whether patients who were previously randomized to high-dose olanzapine (up to 30 mg/day) responded to clozapine.. Thirty three (14 clozapine, 19 olanzapine) (85%) of 39 patients were available for the present 12-week, open-label extension study. Extended safety data using an intention-to-treat analysis from the 14 subjects treated with clozapine for a total of 24 weeks are presented. In addition, we report the clinical outcomes for 10 of 19 olanzapine-treated patients who were switched after 12 weeks to clozapine due to treatment nonresponse. Clinical response was defined as a decrease of 30% or more in total Brief Psychiatric Rating score from week 12 and a Clinical Global Impression-Improvement rating of 1 (very much improved) or 2 (much improved).. The incidence of hypertriglyceridemia (defined as fasting triglycerides >125 mg/dL) (10/14 = 71%) and the incidence of "prediabetes" (defined as fasting blood glucose > or =100) (4/14 = 29%) at week 24 in the clozapine-treated subjects were notable. Seven (70%) of 10 of young patients with schizophrenia who failed treatment with "high-dose" olanzapine were found to respond to a 12-week, open-label clozapine trial.. Clinicians and caregivers need to be aware of potential metabolic adverse events of long-term clozapine treatment. Adolescents with a poor response to olanzapine may do better on clozapine.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Clozapine; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Humans; Hypertriglyceridemia; Lipid Metabolism; Male; Olanzapine; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Previous studies have suggested that clozapine is associated with increases in both weight and serum triglyceride (but not cholesterol) levels. Because of the pharmacologic similarities between clozapine and olanzapine, we decided to evaluate if olanzapine use was associated with an increase in triglycerides.. Twenty-five inpatients (21 men, 4 women) were treated with olanzapine, and their outcomes were tracked prospectively in a medication utilization evaluation study.. After 12 weeks on a mean +/- SD dose of 13.8+/-4.4 mg/day, weight increased a mean of 12 lb (5.4 kg; from 190+/-37 lb [85.5+/-16.7 kg] to 202+/-30 lb [90.9+/-13.5 kg]), while fasting triglycerides increased a mean of 60 mg/dL (from 162+/-121 mg/dL to 222+/-135 mg/dL). Both increases were significant at p < .05. Fasting total cholesterol did not increase. The triglyceride increase was even larger when we excluded 8 patients who received various interventions to lower lipid levels (e.g., pravastatin, low-fat diet) during the olanzapine trial. There was a strong association between weight change and triglyceride change (p < .02); after controlling for weight, analysis of covariance showed no independent increase in triglycerides.. These results suggest olanzapine has significant effects on weight and serum triglyceride levels. Clinical implications are discussed.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dose-Response Relationship, Drug; Female; Hospitalization; Humans; Hypertriglyceridemia; Male; Olanzapine; Pirenzepine; Psychotic Disorders; Schizophrenia; Triglycerides; Weight Gain

Antipsychotic medications increase the risk of abnormal glucose metabolism. However, in clinical practice, it is difficult to predict this risk because it is affected by medication-related and background factors. This study aimed to identify the risk factors for abnormal glucose metabolism during antipsychotic treatment. We conducted a multicenter, prospective, cohort study in patients with schizophrenia, schizoaffective disorder, or bipolar disorder. Of these patients, those with prediabetes or possible diabetes were excluded. Finally, 706 patients were included in the analysis. The hazard ratio (HR) for each factor was calculated for events of progression to hyperglycemia using time-dependent Cox regression analysis stratified according to facility type and adjusted for available background and drug-related factors. Treatments with olanzapine (HR = 2.06, 95% confidence interval [CI] = 1.05-4.05), clozapine (HR = 4.25, 95% CI = 1.56-11.60), and chlorpromazine (HR = 4.48, 95% CI = 1.21-16.57), overweight and obesity (HR = 1.57, 95% CI = 1.02-2.41), and hypertriglyceridemia (HR = 1.72, 95% CI = 1.02-2.88) were associated with a significantly higher occurrence of hyperglycemic progression. The number and daily dose of antipsychotics were not associated with their occurrence. Our study demonstrated that more careful monitoring is necessary during olanzapine, clozapine, and chlorpromazine treatment because of the higher occurrence of abnormalities in glucose metabolism. Furthermore, patients with obesity or hypertriglyceridemia warrant monitoring for the occurrence of abnormal glucose metabolism, regardless of the type of antipsychotic medication.

Topics: Antipsychotic Agents; Benzodiazepines; Chlorpromazine; Clozapine; Cohort Studies; Glucose; Humans; Hypertriglyceridemia; Obesity; Olanzapine; Prospective Studies; Risk Factors

Olanzapine induced a marked elevation in triglyceride and cholesterol levels and in liver transaminase enzymes after 12 weeks of treatment in a patient with schizophrenia. These changes were not seen in an earlier 10-week course of treatment with risperidone, and improved substantially 1 week after the patient stopped olanzapine and began treatment with aripiprazole. The patient did not exhibit weight gain or hyperglycemia with any of the medications. This case and a review of the literature suggest that olanzapine may have unique properties that affect hepatic enzyme pathways, independent of any effects on weight and glucose, that may lead to hyperlipidemia and transaminitis in some patients.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Humans; Hypertriglyceridemia; Liver; Male; Olanzapine; Piperazines; Quinolones; Schizophrenia; Transaminases; Treatment Outcome

Schizophrenic patients treated with clozapine or olanzapine often develop hypertriglyceridemia. The apolipoprotein A5 gene (APOA5), which affects VLDL production and lipolysis, has been implicated in the triglyceride (TG) metabolism. This study examined the association of common APOA5 genetic variants and TG levels in chronically institutionalized schizophrenic patients, on a stable dose of atypical antipsychotic (clozapine, olanzapine or risperidone.. The TG levels in 466 schizophrenic patients treated with clozapine (n = 182), olanzapine (n = 89) or risperidone (n = 195) were measured. Patients were genotyped for the three APOA5 single nucleotide polymorphisms (SNPs) rs662799 (-1131T > C), rs651821 (3A > G) and rs2266788 (1891T > C).. A gene × drug interaction with TG levels was observed. In single-marker-based analysis, the minor alleles of the two polymorphisms (-1131C and -3G) were observed to be associated with increased TGs in patients treated with risperidone, but not with clozapine or olanzapine. Haplotype analysis further revealed that carriers of the haplotype constructed with the three minor alleles had higher TG levels than those who did not carry this haplotype in patients taking risperidone (CGC((+/+)) vs. = 125.4 ± 59.1 vs. 82.2 ± 65.8, P = 0.015; CGC((-/+ )) vs. CGC((-/-)) = 113.7 ± 80.4 vs. 82.2 ± 65.8, P = 0.012).. Our findings extend and add new information to the existing data regarding the association between APOA5 and TG regulation during long-term atypical antipsychotic treatment.

Topics: Adult; Antipsychotic Agents; Apolipoprotein A-V; Apolipoproteins A; Benzodiazepines; Clozapine; Female; Haplotypes; Humans; Hypertriglyceridemia; Male; Middle Aged; Olanzapine; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Risperidone; Schizophrenia; Taiwan; Triglycerides

Polyunsaturated fatty acids (PUFAs) are bimodally distributed in acute schizophrenia, suggesting two endophenotypes. We intended to characterize these endophenotypes clinically. Our a priori hypothesis was that low PUFA patients have more negative symptoms.. Patients (aged 18-39) with schizophrenia, schizoaffective or schizophreniform disorders were recruited at hospital admission during an acute episode. The baseline Positive and Negative Syndrome Scale, vital signs and biochemical variables were measured in 97 patients with available RBC PUFA levels. Adjustment for multiple testing was not performed.. The median Negative Subscale score was higher (p=0.04) in the low PUFA (25 points, n=30) than in the high PUFA group (19 points, n=67). Among 95 patients with measurements of serum triglycerides, hypertriglyceridaemia was more prevalent (p=0.009) among low PUFA patients (66%) than high PUFA patients (36%). PUFA modified the effect of antipsychotics on triglycerides (p=0.046). Serum glucose and mean corpuscular haemoglobin were higher (p=0.03, 0.001, respectively) in low PUFA than in high PUFA patients. Low PUFA men were heavier (p=0.04) than high PUFA men.. During an acute episode of schizophrenia, patients with low RBC PUFA have more negative symptoms and more metabolic and haematological abnormalities than those with high PUFA. This indicates that PUFA levels define two clinically distinct endophenotypes of the disorder.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Biomarkers; Clozapine; Dibenzothiazepines; Endophenotypes; Erythrocytes; Fatty Acids, Unsaturated; Female; Humans; Hypertriglyceridemia; Linear Models; Logistic Models; Male; Obesity; Olanzapine; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology

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

Second-generation antipsychotics can cause lipid elevations at a greater rate than older typical antipsychotics. This risk may not be equivalent amongst the second-generation antipsychotics. We conducted a computerized, retrospective, nonrandomized, case-control analysis of 6331 patients receiving antipsychotics. For each patient, the first prescription for at least 60 continuous days for four antipsychotics [haloperidol (HALD), olanzapine (OLANZ), quetiapine (QUET), or risperidone (RISP)] was analyzed for total cholesterol, low-density lipoprotein, high-density lipoprotein (HDL), and triglycerides (TGL). Mean HDL was lower during OLANZ treatment than with RISP (P = 0.03) or QUET (P = 0.001). TGL were higher during OLANZ (P = 0.0007) or QUET treatment (P = 0.006) than RISP. In dichotomous analyses, odds ratios on the percentage of participants having abnormal cholesterol (P = 0.0003), low-density lipoprotein (P = 0.001), or TGL (P = 0.0001) during medication were in the order: OLANZ > QUET > RISP > HALD. For HDL, the results were less robust but the percentage of participants were in the order: OLANZ>RISP = HALD = QUET. In treatment-emergent analyses of patients without lipid abnormalities during an unmedicated baseline period, there was a greater risk of developing new HDL abnormality with OLANZ than RISP (P<0.05). In conclusion, treatment with RISP or HALD was associated with a more favorable lipid profile than with OLANZ or QUET.

Topics: Antipsychotic Agents; Benzodiazepines; Case-Control Studies; Dibenzothiazepines; Dyslipidemias; Female; Haloperidol; Humans; Hypertriglyceridemia; Male; Olanzapine; Quetiapine Fumarate; Retrospective Studies; Risk Assessment; Risperidone; Time Factors; United States; United States Department of Veterans Affairs

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

We encountered a case where treatment with olanzapine resulted in the elevation of serum triglyceride level despite the absence of weight gain and abnormal glucose metabolism. Elevation in serum triglyceride levels as seen in non-obese individuals does not fall under the category of metabolic syndrome which has recently been highlighted as an adverse reaction to second-generation antipsychotics. In some individuals treated with antipsychotics, metabolic abnormalities develop with an initial sign of elevated serum triglyceride levels instead of weight gain.

Topics: Antipsychotic Agents; Benzodiazepines; Humans; Hypertriglyceridemia; Male; Middle Aged; Olanzapine; Schizophrenia; Treatment Outcome; Triglycerides

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Humans; Hypertriglyceridemia; Lipoprotein Lipase; Male; Olanzapine; Risk Factors; Schizophrenia

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dose-Response Relationship, Drug; Humans; Hypertriglyceridemia; Male; Obesity; Olanzapine; Schizophrenia; Weight Gain

It is important to assess cardiovascular risk factors to properly verify the potential consequences of atypical antipsychotic-related weight gain. The objective of the present study was to evaluate whether 2 atypical antipsychotics differ regarding their impact on the cardiovascular disease risk profile compared with a reference group.. We conducted a cross-sectional, multicenter study to assess anthropometric indices of obesity and to obtain a comprehensive fasting metabolic risk profile. Either risperidone or olanzapine had to be prescribed as the first and only antipsychotic for a minimum of 6 months. Patients were compared with a reference group of nondiabetic men. Data were collected from August 1999 to August 2001.. Eighty-seven patients treated with olanzapine (N = 42) or risperidone (N = 45) were evaluated. Olanzapine-treated patients had significantly higher plasma triglyceride concentrations (2.01 +/-1.05 vs. 1.34 +/-0.65 mmol/L, p < or =.05), lower high-density lipoprotein (HDL)-cholesterol levels (0.92 +/-0.17 vs. 1.04 +/- 0.21 mmol/L, p < or =.05), higher cholesterol/HDL-cholesterol ratios (5.62 +/-1.70 vs. 4.50 +/- 1.44, p < or =.05), higher apolipoprotein B levels (1.07 +/- 0.35 vs. 0.92 +/- 0.27 g/L, p < or =.05), smaller low-density lipoprotein peak particle diameters (252.6 +/-4.1 vs. 255.2 +/-4.3 A, p <.01), and higher fasting insulin concentrations (103.9 +/- 67.6 vs. 87.5 +/- 56.1 pmol/L, p < or =.05) than risperidone-treated patients. Moreover, 33% of olanzapine-treated patients were carriers of 3 atherogenic features of the metabolic syndrome as opposed to a prevalence of only 11% of risperidone-treated patients.. These results suggest that olanzapine-treated patients are characterized by a more deteriorated metabolic risk factor profile compared with risperidone-treated patients. These observations raise concerns about the potential differential long-term deleterious effects of some antipsychotics, such as olanzapine, on cardiovascular health.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Biomarkers; Carrier State; Cholesterol, HDL; Coronary Artery Disease; Cross-Sectional Studies; Factor Analysis, Statistical; Fasting; Health Surveys; Humans; Hypertriglyceridemia; Insulin; Male; Metabolic Syndrome; Obesity; Olanzapine; Prevalence; Psychotic Disorders; Risk Factors; Risperidone; Weight Gain

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Hospitalization; Humans; Hypertriglyceridemia; Male; Olanzapine; Pirenzepine; Schizophrenia, Paranoid; Severity of Illness Index

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Child; Humans; Hypertriglyceridemia; Male; Olanzapine; Pirenzepine; Weight Gain

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

Olanzapine is an atypical antipsychotic that is becoming more widely used in children and adolescents. There have been reports of olanzapine-induced hyperglycemia and hypertriglyceridemia in adults. This case report describes the development of both hyperglycemia and hypertriglyceridemia in a male adolescent that resolved with discontinuation of olanzapine and without dietary changes or the use of insulin or oral hypoglycemics.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Humans; Hyperglycemia; Hypertriglyceridemia; Male; Mental Disorders; Olanzapine; Pirenzepine

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Hypertriglyceridemia; Male; Middle Aged; Olanzapine; Pirenzepine; Schizophrenia; Triglycerides; Weight Gain