olanzapine and Metabolic-Syndrome

Psychosis is a state of mind that makes it difficult to determine what is real and what is not. Psychosis can have serious negative effects. Like many psychiatric phenomena, psychosis has a variety of causes, such as schizophrenia, bipolar disorder, and psychotic depression. Antipsychotic medications, psychotherapy, and social support are the most common treatments. Antipsychotic drugs reduce the symptoms of psychosis by changing brain chemistry. Based on the mechanism of action, antipsychotics have two groups, typical and atypical. Most people who take antipsychotics experience side effects. People taking typical antipsychotics tend to have higher rates of extrapyramidal side effects, but some atypical drugs, especially olanzapine, are associated with the risk of significant weight gain, diabetes, and metabolic syndrome, which, in turn, increases the risk of atherosclerotic cardiovascular disease and premature death. Physical exercise, diet regimen, psychoeducation, monotherapy, or switching to an alternative antipsychotic are strategies to correct metabolic aberrates in atypical antipsychotic users. In light of several successful studies on the use of medicinal plants to control metabolic syndrome, this article briefly reviews the studies on some herbal medications for the management of metabolic disorders associated with atypical antipsychotics and discusses probable mechanisms. Therefore, we searched the Cochrane, Scopus, PubMed, and Google Scholar databases for works published before July, 2022, on the effect of herbal medications on antipsychotic-related metabolic abnormalities in animals or humans. We recommend that some herbal medicines may be efficient for regulating the metabolic changes related to atypical antipsychotics due to their multipotential action, and more efforts should be made to make herbal drug treatments more effective. We hope this review will be a reference for research on developing herbal therapeutics for metabolic alterations in antipsychotic customers.

Topics: Animals; Antipsychotic Agents; Humans; Metabolic Syndrome; Olanzapine; Schizophrenia; Weight Gain

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

Topics: Antipsychotic Agents; Cardiometabolic Risk Factors; Drug Therapy, Combination; Female; Humans; Male; Metabolic Syndrome; Naltrexone; Olanzapine; Schizophrenia; Weight Gain

This systematic review aimed to determine whether olanzapine is more likely than other second-generation antipsychotics (SGAs) to induce insulin resistance in patients with schizophrenia in China.. We reviewed all randomized controlled trials on insulin resistance and metabolic abnormalities caused by SGAs in the PubMed, China National Knowledge Infrastructure (CNKI), VIP, and Wanfang databases. Retrieved articles were published on or before December 2018. Meta-analysis was performed to determine the effect size of the treatment on the insulin resistance index (IRI), fasting blood glucose (FBG), and fasting insulin (FINS).. Forty studies (3725 participants in total) were included. All studies contained data suitable for comparing aripiprazole vs. olanzapine, ziprasidone vs. olanzapine, and risperidone vs. olanzapine. Patients treated with olanzapine had higher IRI, FBG, and FINS levels than did patients treated with aripiprazole, ziprasidone, or risperidone, with significant differences (aripiprazole vs. olanzapine: FBG: standardized mean difference [SMD] = 0.72, 95% confidence interval [95%CI] - 0.82, - 0.61; FINS: SMD = - 0.8, 95%CI - 1.00, - 0.61; IRI: SMD = - 0.80, 95%CI - 0.99, - 0.61; ziprasidone vs. olanzapine: FBG: SMD = - 1.19, 95%CI - 1.30, - 1.08; FINS: SMD = - 0.66, 95%CI - 0.85, - 0.47; IRI: SMD = - 0.71, 95%CI - 0.88, - 0.55; risperidone vs. olanzapine: FBG: SMD = - 0.17, 95%CI - 0.34, - 0.00).. Existing data suggest that olanzapine is associated with a significantly greater risk of IRI, FBG, and FINS, while other agents are associated with relatively lower risks. Thus, olanzapine is more likely to induce insulin resistance than are other SGAs in schizophrenic patients in China.

Topics: Antipsychotic Agents; China; Humans; Insulin Resistance; Metabolic Syndrome; Olanzapine; Schizophrenia

Schizophrenia is associated with an increased prevalence of the metabolic syndrome. Patients receiving antipsychotic medications, including olanzapine, are at further risk. Ghrelin is an appetite-stimulating peptide hormone, although whether blood levels are altered by antipsychotic treatment, remains unclear. We performed a systematic review and meta-analysis comparing blood ghrelin levels in patients with schizophrenia before and after treatment with olanzapine.. Two authors independently searched major electronic databases from inception until February 2018 for studies measuring blood ghrelin levels among patients with schizophrenia before and after olanzapine therapy. Random effects meta-analysis calculating standardized mean difference (SMD) and 95% confidence intervals (CI) and meta-regression analyses were performed.. Six studies met the inclusion criteria. Across these studies, there were 111 patients with schizophrenia (mean age 40, 85% male, baseline BMI 22, and endpoint BMI 23). Olanzapine treatment (mean [standard deviation] duration = 12.3 [7.6] weeks) was associated with a significant decrease in blood ghrelin levels with a medium effect size (SMD = -0.48, 95% CI -0.88 to -0.08, p = 0.018). Age, sex, baseline BMI, geography, olanzapine dose and duration, year of publication, study quality, inpatient status, and antipsychotic washout did not moderate this association.. Our results suggest that in patients with schizophrenia, olanzapine therapy is associated with decreased blood ghrelin levels, a paradoxical phenomenon known to occur in obesity. Future studies should investigate the contribution of dietary factors (e.g., caloric intake) and physical activity to this association, as well as the effects of other antipsychotics on ghrelin levels.

Topics: Antipsychotic Agents; Ghrelin; Humans; Metabolic Syndrome; Obesity; Olanzapine; Schizophrenia

Behavioral and psychological symptoms of dementia pose management challenges for caregivers and clinicians. Firstline nonpharmacologic treatments include eliminating physical and emotional stressors, modifying the patient's environment, and establishing daily routines. Family members and caregivers benefit from education about dementia symptoms and reminders that the behaviors are normal and unintentional. Cognitive and emotion-oriented interventions, sensory stimulation interventions, behavior management techniques, and other psychosocial interventions are modestly effective. In refractory cases, physicians may choose to prescribe off-label antipsychotics. Aripiprazole has the most consistent evidence of symptom improvement; however, this improvement is small. Olanzapine, quetiapine, and risperidone have inconsistent evidence of benefit. Physicians should use the smallest effective dose for the shortest possible duration to minimize adverse effects, most notably an increased mortality risk. Other adverse effects include anticholinergic and antidopaminergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, postural hypotension, metabolic syndrome, cardiac arrhythmia, and sedation. Patients should be monitored for these effects while receiving treatment; however, laboratory monitoring may be limited to patients receiving long-term therapy.

Topics: Antipsychotic Agents; Aripiprazole; Arrhythmias, Cardiac; Basal Ganglia Diseases; Behavior Therapy; Benzodiazepines; Cognitive Behavioral Therapy; Dementia; Emotions; Humans; Hypotension, Orthostatic; Metabolic Syndrome; Neuroleptic Malignant Syndrome; Olanzapine; Practice Guidelines as Topic; Psychotic Disorders; Quetiapine Fumarate; Risperidone

To conduct meta-analyses of all published association studies on the HTR2C -759C/T (rs3813829) polymorphism and olanzapine-induced weight gain in schizophrenia patients and on the HTR2C -759C/T, -697G/C (rs518147) and rs1414334:C> G polymorphisms and olanzapine/clozapine/risperidone-induced metabolic syndrome in schizophrenia patients.. Eligible studies were identified by searching PubMed and Web of Science databases. Meta-analyses were performed using Cochrane Review Manager (RevMan, version 5.2) to calculate the pooled odds ratio (OR) and its corresponding 95% confidence interval (CI).. Our meta-analyses revealed both a significant positive association between the rs1414334 C allele and olanzapine/clozapine/risperidone-induced metabolic syndrome and a marginally significant positive association between the -697C allele and the induced metabolic syndrome in schizophrenia patients, but no significant association between the -759C/T polymorphism and the induced metabolic syndrome in schizophrenia patients. Our analysis further revealed a pronounced trend toward a significant negative association between the -759T allele and high olanzapine-induced weight gain and a trend toward a significant positive association between the -759C allele and high olanzapine-induced weight gain in Caucasian schizophrenia patients.. Our results support that HTR2C polymorphisms play a role in antipsychotic-induced metabolic disturbance. More association studies are needed to further elucidate association of different HTR2C polymorphisms and antipsychotic-induced metabolic disturbance.

Topics: Alleles; Antipsychotic Agents; Benzodiazepines; Clozapine; Female; Genetic Association Studies; Humans; Male; Metabolic Syndrome; Olanzapine; Polymorphism, Single Nucleotide; Receptor, Serotonin, 5-HT2C; Risperidone; Schizophrenia; Weight Gain

Patients with schizophrenia have a shorter life expectancy and their risk of dying from a cardiovascular disease is higher than the general population. Both facts have been attributed to the raised presence of metabolic syndrome. There is a big amount of scientific publications that deals with the relationship between schizophrenia, antipsychotic treatment, and the development of metabolic syndrome. There is also information about recommendations and clinical guides to achieve an adequate prevention, screening, and treatment of the disease. The aim of this review is to update the current information about this issue and to understand related etiologic factors, differences between antipsychotic drugs, and the current recommendations for patient's care.

Topics: Antipsychotic Agents; Benzodiazepines; Blood Glucose; Cardiovascular Diseases; Clozapine; Comorbidity; Follow-Up Studies; Humans; Hypothalamus; Incidence; Life Expectancy; Lipid Metabolism; Metabolic Syndrome; Obesity, Abdominal; Olanzapine; Practice Guidelines as Topic; Schizophrenia; Weight Gain

Metabolic syndrome and cardiovascular diseases are important causes of morbidity and mortality among patients with severe mental illnesses. Atypical or second-generation antipsychotics (SGAs) are associated with obesity and other components of metabolic syndrome, particularly abnormal glucose and lipid metabolism. This review aims to provide a summary of recent evidence on metabolic risks associated with SGAs, current recommendations for metabolic monitoring, and efficacy of treatment options currently available.. Studies have identified younger, antipsychotic-naive patients with first-episode psychosis as a population vulnerable to adverse metabolic effects from SGAs. These patients gained more weight and developed evident lipid and glucose abnormalities as soon as 8-12 weeks after treatment initiation. Findings are more striking among children and adolescents. The differential effects of various SGAs are well described, with clozapine and olanzapine associated with the highest metabolic risk. In addition to behavioral therapy, emerging data suggest that pharmacological therapy, most notably metformin, is efficacious in the treatment and possibly prevention of SGA-associated metabolic derangements.. More data have become available on the burden from metabolic complications associated with SGAs. New and effective treatment options are required in the near future to improve cardiovascular health in this susceptible population.

Topics: Antipsychotic Agents; Benzodiazepines; Cardiovascular Diseases; Clozapine; Humans; Metabolic Syndrome; Metformin; Obesity; Olanzapine; Practice Guidelines as Topic; Psychotic Disorders; Severity of Illness Index; Weight Gain

Topics: Aged; Antipsychotic Agents; Aripiprazole; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Diagnosis, Differential; Female; Humans; Metabolic Syndrome; Middle Aged; Olanzapine; Pain; Patient Compliance; Peripheral Nervous System Diseases; Piperazines; Quinolones; Schizophrenia, Paranoid; Skin Diseases, Parasitic; Sleep Wake Disorders

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

Weight gain and adverse cardiometabolic effects often limit the clinical utility of olanzapine. In ENLIGHTEN-2, combining olanzapine with the opioid receptor antagonist samidorphan (OLZ/SAM) mitigated olanzapine-associated weight gain. These analyses tested the hypothesis that OLZ/SAM would be associated with reduced adverse cardiometabolic effects compared with olanzapine.. This phase 3 double-blind study randomized adults with schizophrenia to OLZ/SAM or olanzapine for 24 weeks. Post hoc analyses assessed changes from baseline to week 24 in cardiometabolic risk parameters, including body mass index (BMI), risk of developing obesity (BMI ≥30 kg/m2) or metabolic syndrome, waist circumference, along with mean and potentially clinically significant changes in blood pressure, glucose, and lipids.. After 24 weeks' treatment, compared with olanzapine, OLZ/SAM was associated with smaller least-squares mean (LSM) changes from baseline in systolic blood pressure (LSM difference, -2.63 mm Hg; 95% CI: -4.78, -0.47), diastolic blood pressure (LSM difference, -0.75 mm Hg; 95% CI: -2.31, 0.80), and BMI (LSM difference, -0.65 kg/m2; 95% CI: -1.01, -0.28). OLZ/SAM treatment was also associated with reduced risk of shifting from normal blood pressure to stage 1/2 hypertension (odds ratio [OR], 0.48; 95% CI: 0.24, 0.96), becoming obese (OR, 0.52; 95% CI: 0.32, 0.82), and developing metabolic syndrome (OR, 0.55; 95% CI: 0.31, 0.99) compared with olanzapine. No treatment group differences were noted for risk of hyperglycemia or hyperlipidemia.. OLZ/SAM treatment was associated with lower risk of worsening cardiometabolic risk factors related to obesity, hypertension, and metabolic syndrome relative to olanzapine. NCT02694328, https://clinicaltrials.gov/ct2/show/NCT02694328.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cardiometabolic Risk Factors; Cardiovascular Diseases; Humans; Hypertension; Metabolic Syndrome; Obesity; Olanzapine; Weight Gain

To compare longitudinal metabolic effects of 7 antipsychotics, including body mass index (BMI), waist circumference (WC), blood pressure (BP), glucose, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C); to investigate risk factors for metabolic syndrome (MetS); and to make recommendations on frequency and timing of monitoring metabolic measurements.. This randomized, open-label, pharmacologic trial was conducted among patients with schizophrenia (DSM-IV) in 32 hospitals across China. Patients were randomly assigned to 7 groups and assessed at baseline, 2, 4, and 6 weeks. Linear mixed-effect models were used to assess changes of metabolic measures over time. Multivariable logistic regression analysis was performed to investigate the risk factors for MetS.. In total, 2,550 (718 drug-naïve) of 2,774 patients finished the study between July 6, 2010, and November 30, 2011. We found significant (P < .05) changes for BMI, WC, TG, and LDL-C, with TG and LDL-C reaching a plateau. Interactions between baseline metabolic condition and changes over time were observed for BMI (χ² = 43.11, P < .001), WC (χ² = 36.34, P < .001), systolic BP (χ² = 11.92, P = .002), glucose (χ² = 6.09, P = .01), and TG (χ² = 6.01, P = .01). Antipsychotics generally had greater adverse effects on patients who were initially screened as metabolically normal. After controlling for other associated factors, we found that antipsychotics resulted in differing risk for incident MetS, with a similar pattern to findings in other populations: olanzapine (odds ratio [OR] = 3.36, P < .001) > quetiapine (OR = 3.29, P < .001) > perphenazine (OR = 2.73, P = .007) > risperidone (OR = 2.21, P = .02) > aripiprazole (OR = 1.74, P = .15) ≈ haloperidol (OR = 1.75, P = .22) ≈ ziprasidone (OR = 1, reference).. Metabolic traits should be monitored frequently in early stages of antipsychotic treatment due to rapid and substantial changes. Clinicians should not assume low risk for patients with normal metabolic parameters at baseline.. Chinese Clinical Trial Registry identifier: ChiCTR-TRC-10000934.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Blood Glucose; Cholesterol, HDL; Cholesterol, LDL; Female; Humans; Male; Metabolic Syndrome; Olanzapine; Piperazines; Quetiapine Fumarate; Risk Factors; Risperidone; Schizophrenia; Thiazoles; Triglycerides

Our previous study showed that metabolic abnormalities reduced the levels of brain-derived neurotrophic factor (BDNF) and deteriorated cognitive performance in patients with schizophrenia. Inflammation may play a key role in this process. Omega-3 fatty acids have been documented to ameliorate inflammation. Therefore, we hypothesized that omega-3 fatty acids may be of value in enhancing BDNF levels and improving cognitive function in patients with schizophrenia with metabolic syndrome (MetS). We recruited 80 patients with both schizophrenia and MetS who received long-term olanzapine monotherapy. The enzyme-linked immunosorbent assay was used to measure the plasma levels of C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). The patients were randomly assigned to the OMG-3 group (n = 40) or the placebo group (n = 40). Of the 80 patients who consented to the study, 72 completed this 12-week RCT. The primary outcome was the changes from baseline to 12 weeks in clinical characteristics and the levels of BDNF, CRP, IL-6 and TNF-α. There was a significant correlation between omega-3 fatty acid treatment and enhanced delayed memory factor in the RBANS assessment (F

Topics: Cognitive Dysfunction; Fatty Acids, Omega-3; Humans; Metabolic Syndrome; Olanzapine; Schizophrenia

With the second-generation antipsychotics (SGAs) widely applied to treat patients with schizophrenia, adverse effects, especially the metabolic syndrome (MetS), were paid more attention following by the efficacy of SGAs. Several studies have suggested that acupuncture could be an effective and safe intervention for MetS. Here, we present a study protocol to investigate the effect of electroacupuncture on MetS due to olanzapine and risperidone.. This study is a prospective, randomized, single-centered, patient-assessor-blinded, parallel-controlled clinical pilot trial. In all, 36 patients will be randomized to an experimental group or control group by a 1:1 ratio. All patients will receive lifestyle interventions. The experimental group will receive electroacupuncture treatment. The control group will receive sham electroacupuncture treatment. The primary outcomes are body mass index (BMI) and waist circumference (WC). The secondary outcome measures include blood pressure (BP), fasting blood glucose (FBG), triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), leptin, and adiponectin. We will assess at baseline, 8 weeks after intervention and at the end of 3 months' follow-up.. The results of this trial are expected to provide data on the efficacy and safety of electroacupuncture on MetS due to olanzapine and risperidone, and potential biochemical mechanism.

Topics: Antipsychotic Agents; Clinical Protocols; Electroacupuncture; Humans; Metabolic Syndrome; Olanzapine; Risperidone; Schizophrenia

Individuals with schizophrenia are at increased risk of developing metabolic syndrome (MetS) due to their lifestyle and antipsychotic treatment. Our previous study showed that patients with both schizophrenia and MetS present an increased expression and production of tumor necrosis factor-alpha (TNF-alpha). Omega-3 fatty acids have a documented role in suppressing TNF-alpha; therefore, we hypothesized that they may be of value in relieving inflammation and improving metabolic disturbance in patients with both schizophrenia and MetS.. This study employed a randomized placebo-controlled trial to investigate the effects of omega-3 fatty acids on MetS in patients with schizophrenia.. We recruited 80 patients with both schizophrenia and MetS who received long-term olanzapine monotherapy. The patients were randomly assigned to the OMG-3 group (n = 40) or the placebo group (n = 40).. Our findings provide suggestive evidence that omega-3 fatty acids have beneficial effects on TG metabolism in patients with both schizophrenia and MetS that parallel decreased inflammation levels.

Topics: Adult; Antipsychotic Agents; Biomarkers; Dietary Supplements; Fatty Acids, Omega-3; Female; Humans; Male; Metabolic Syndrome; Middle Aged; Olanzapine; Schizophrenia; Time Factors; Treatment Outcome; Triglycerides; Tumor Necrosis Factor-alpha

It is unknown whether there are differences in efficacy and safety between quetiapine extended-release, 300 mg/d (QUEXR300), and olanzapine, 5-20 mg/d (OLA), for Japanese patients with bipolar depression.. We conducted a Bayesian analysis of data from phase 3 studies in Japan of QUEXR300 and OLA. Outcomes were remission rate (primary), response rate, improvement on the Montgomery-Åsberg Depression Rating Scale and 17-item Hamilton Depression Rating Scale scores, discontinuation rate, and incidence of individual adverse events. We calculated the standardized mean difference (SMD) and the risk ratio (RR) and 95% credible interval (95% CrI) for continuous and dichotomous data, respectively.. There were no significant differences between QUEXR300 and OLA for any of the efficacy outcomes. QUEXR300 was associated with a higher incidence of somnolence than OLA (RR = 5.517; 95% CrI = 1.563, 19.787), while OLA was associated with greater increase body weight (SMD = -0.488; 95% CrI = -0.881, -0.089) and blood prolactin levels (SMD = -0.642; 95% CrI = -1.073, -0.213) than QUEXR300, and a greater decrease in high-density lipoprotein cholesterol levels (SMD = -0.408; 95% CrI = -0.785, -0.030) than QUEXR300.. Although the two drugs' efficacy did not differ, OLA increased the risk of metabolic syndrome and QUEXR300 the risk of somnolence. A large scale, long-term, head-to-head comparison study of QUEXR300 vs OLA for Japanese patients with bipolar depression is needed to confirm the results of the current study.

Topics: Adolescent; Adult; Antipsychotic Agents; Bayes Theorem; Bipolar Disorder; Cholesterol, HDL; Delayed-Action Preparations; Female; Humans; Japan; Male; Metabolic Syndrome; Middle Aged; Olanzapine; Prolactin; Quetiapine Fumarate; Weight Gain

Ziprasidone (ZIP) is often used with olanzapine (OLZ) in 'switch' and combination therapy but empirical evidence to support these strategies is limited.. This study was therefore designed to compare the efficacy and tolerability of switching from OLZ to ZIP, the combination of both medications, and OLZ and ZIP monotherapy, in patients with schizophrenia spectrum disorders (SSD).. In this 12 week open-label, assessor-blinded randomized trial, 148 patients with SSD who had not used antipsychotics for at least 3 months were assigned to ZIP (n = 49) or OLZ monotherapy (n = 31); OLZ for 4 weeks then a switch to ZIP (OLZ/ZIP, n = 35); or combination therapy (OLZ + ZIP, n = 33). The severity of psychosis and abnormal involuntary movements was evaluated at baseline, 1, 2, 4, 8, and 12 weeks using standard instruments. Baseline-to-endpoint changes in weight gain and metabolic measures were compared.. The efficacy of both OLZ/ZIP and OLZ + ZIP was comparable OLZ monotherapy and better than ZIP monotherapy in reducing overall psychotic and negative symptoms at most 8 and 12 week measurement points. Changes in weight gain, glucose, and lipid measures did not differ between OLZ/ZIP and OLZ + ZIP, but were markedly higher following OLZ monotherapy. The OLZ + ZIP group had the lowest overall incidence of adverse events and extrapyramidal symptoms of all the treatment regimens.. We conclude that combining ZIP and OLZ at the outset of treatment is superior to switching from OLZ to ZIP in terms of improving psychotic symptoms and limiting movement side effects without increasing the risk of metabolic syndrome.

Topics: Administration, Oral; Adult; Antipsychotic Agents; Benzodiazepines; Drug Substitution; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Female; Humans; Male; Metabolic Syndrome; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Severity of Illness Index; Single-Blind Method; Thiazoles; Treatment Outcome; Weight Gain

To determine whether the prescription of aripiprazole, compared with olanzapine and haloperidol, was associated with a lower frequency of metabolic syndrome (MS) and treatment discontinuation at 1 year.. Patients were randomly assigned to be treated open-label and according to usual clinical practice with either aripiprazole, olanzapine, or haloperidol and followed up for 1 year.. Three hundred out-patients with persistent schizophrenia were recruited in 35 mental health services. The intention-to-treat (ITT) analysis found no significant differences in the rate of MS between aripiprazole (37%), olanzapine (47%), and haloperidol (42%). Treatment discontinuation for any cause was higher for aripiprazole (52%) than for olanzapine (33%; OR, 0.41; P = 0.004), or haloperidol (37%; OR, 0.51; P = 0.030). No significant difference was found between olanzapine and haloperidol. Time to discontinuation for any cause was longer for olanzapine than for aripiprazole (HR, 0.55; P < 0.001). No significant differences were found between haloperidol and aripiprazole, or between olanzapine and haloperidol.. The prescription of aripiprazole did not significantly reduce the rates of MS, but its treatment retention was worse. Aripiprazole cannot be considered the safest and most effective drug for maintenance treatment of schizophrenia in routine care, although it may have a place in antipsychotic therapy.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Female; Follow-Up Studies; Haloperidol; Humans; Male; Metabolic Syndrome; Middle Aged; Olanzapine; Schizophrenia; Treatment Outcome

The aim of this study was to assess whether saffron aqueous extract (SAE) or its active constituent, crocin, prevents olanzapine-induced metabolic syndrome (MetS) and insulin resistance in patients with schizophrenia.. 66 patients diagnosed with schizophrenia who were on olanzapine treatment (5-20 mg daily) were randomly allocated to receive a capsule of SAE (n=22; 30 mg daily), crocin (n=22; 30 mg daily) or placebo (n=22) in a 12-week triple-blind trial. Patients were screened not to have MetS at baseline and further assessment was done at weeks 6 and 12. Measurement of fasting blood glucose (FBS) and serum lipids were repeated at weeks 2, 6 and 12. Fasting blood levels of insulin and HbA1c were also measured at baseline and week 12. HOMA-IR and HOMA-β were determined to evaluate insulin resistance.. 61 patients completed the trial and no serious adverse effects were reported. Time-treatment interaction showed a significant difference in FBS in both SAE and crocin groups compared to placebo (p=0.004). In addition, SAE could effectively prevent reaching the criteria of metabolic syndrome (0 patients) compared to crocin (9.1%) and placebo (27.3%) as early as week 6.. SAE could prevent metabolic syndrome compared to crocin and placebo. Furthermore, both SAE and crocin prevented increases in blood glucose during the study.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Carotenoids; Crocus; Double-Blind Method; Humans; Insulin Resistance; Male; Metabolic Syndrome; Middle Aged; Olanzapine; Plant Extracts; Schizophrenia; Waist Circumference

This study examined the clinical significance of switching from olanzapine, quetiapine, or risperidone to aripiprazole by examining changes in predicted risk of cardiovascular disease (CVD) according to the Framingham Risk Score (FRS) and metabolic syndrome status. FRS estimates 10-year risk of "hard" coronary heart disease (CHD) outcomes (myocardial infarction and coronary death) while metabolic syndrome is associated with increased risk of CVD, stroke, and diabetes mellitus.. Changes in FRS and metabolic syndrome status were compared between patients with BMI ≥ 27 and non-HDL-C ≥ 130 mg/dL randomly assigned to stay on stable current treatment (olanzapine, quetiapine, or risperidone) or switch to treatment with aripiprazole with 24 weeks of follow-up. All study participants were enrolled in a behavioral program that promoted healthy diet and exercise.. The pre-specified analyses included 89 switchers and 98 stayers who had post-baseline measurements needed to assess changes. Least squares mean estimates of 10-year CHD risk decreased more for the switch (from 7.0% to 5.2%) than the stay group (from 7.4% to 6.4%) (p = 0.0429). The odds ratio for having metabolic syndrome (stay vs. switch) at the last observation was 1.748 (95% CI 0.919, 3.324, p = 0.0885).. Switching from olanzapine, quetiapine, or risperidone to aripiprazole was associated with larger reductions in predicted 10-year risk of CHD than the behavioral program alone. The advantage of switching on metabolic syndrome was not statistically significant. The benefits of switching must be balanced against its risks, which in this study included more discontinuations of the study treatment but no significant increase in symptoms or hospitalizations.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Coronary Artery Disease; Dibenzothiazepines; Drug Substitution; Female; Humans; Longitudinal Studies; Male; Metabolic Syndrome; Middle Aged; Multicenter Studies as Topic; Odds Ratio; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone

To compare longer-term safety and effectiveness of the 4 most commonly used atypical antipsychotics (aripiprazole, olanzapine, quetiapine, and risperidone) in 332 patients, aged > 40 years, having psychosis associated with schizophrenia, mood disorders, posttraumatic stress disorder, or dementia, diagnosed using DSM-IV-TR criteria.. We used equipoise-stratified randomization (a hybrid of complete randomization and clinician's choice methods) that allowed patients or their treating psychiatrists to exclude 1 or 2 of the study atypical antipsychotics due to past experience or anticipated risk. Patients were followed for up to 2 years, with assessments at baseline, 6 weeks, 12 weeks, and every 12 weeks thereafter. Medications were administered employing open-label design and flexible dosages, but with blind raters. The study was conducted from October 2005 to October 2010.. Primary metabolic markers (body mass index, blood pressure, fasting blood glucose, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides), percentage of patients who stay on the randomly assigned atypical antipsychotic for at least 6 months, psychopathology, percentage of patients who develop metabolic syndrome, and percentage of patients who develop serious and nonserious adverse events.. Because of a high incidence of serious adverse events, quetiapine was discontinued midway through the trial. There were significant differences among patients willing to be randomized to different atypical antipsychotics (P < .01), suggesting that treating clinicians tended to exclude olanzapine and prefer aripiprazole as one of the possible choices in patients with metabolic problems. Yet, the atypical antipsychotic groups did not differ in longitudinal changes in metabolic parameters or on most other outcome measures. Overall results suggested a high discontinuation rate (median duration 26 weeks prior to discontinuation), lack of significant improvement in psychopathology, and high cumulative incidence of metabolic syndrome (36.5% in 1 year) and of serious (23.7%) and nonserious (50.8%) adverse events for all atypical antipsychotics in the study.. Employing a study design that closely mimicked clinical practice, we found a lack of effectiveness and a high incidence of side effects with 4 commonly prescribed atypical antipsychotics across diagnostic groups in patients over age 40, with relatively few differences among the drugs. Caution in the use of these drugs is warranted in middle-aged and older patients.. ClinicalTrials.gov identifier: NCT00245206.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Biomarkers; Blood Glucose; Blood Pressure; Body Mass Index; Cholesterol; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Male; Metabolic Syndrome; Middle Aged; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Therapeutic Equipoise; Triglycerides; United States

Metabolic effects are generally more pronounced with second-generation than first-generation antipsychotics. This study was designed to compare long-term metabolic effects and efficacy of paliperidone extended release (ER) with those of oral olanzapine in patients with schizophrenia. In this 6-month, multicenter, prospective, randomized, controlled, open-label, parallel-group study, adults with schizophrenia were treated with paliperidone ER (6-9 mg/d; n = 239) or oral olanzapine (10-15 mg/d; n = 220). The primary outcome was mean change in the ratio of serum triglyceride level to high-density lipoprotein level (TG/HDL), a marker of insulin resistance. Other outcome measures included the Positive and Negative Syndrome Scale scores, measures of lipid and glucose metabolism, and body weight. Significant improvements in psychotic symptoms were observed with both treatments (P < 0.0001). The TG/HDL ratio was significantly higher at end point versus baseline with olanzapine compared with that of paliperidone ER. Mean end point change in TG/HDL ratio was 0.97 ± 2.72 [corrected] for olanzapine (P < 0.0001, reflecting worsening), with no significant change for paliperidone ER (-0.17 ± 2.51). Newly diagnosed impairment in TG and metabolic syndrome was more common with olanzapine (P < 0.05). Insulin resistance, as measured by the homeostasis model assessment of insulin resistance, worsened significantly with olanzapine (P = 0.0003), but not with paliperidone ER. Glucose sensitivity for insulin worsened significantly with olanzapine (P < 0.03), with no significant changes for paliperidone ER. End point increase in body weight was significantly higher with olanzapine than paliperidone ER (3.8 vs 1.2 kg; P = 0.0013). In summary, both paliperidone ER and olanzapine effectively treated schizophrenia; however, undesirable metabolic effects were significantly greater with olanzapine.

Topics: Administration, Oral; Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Body Weight; Delayed-Action Preparations; Female; Glucose Tolerance Test; Humans; Isoxazoles; Lipoproteins, HDL; Male; Metabolic Syndrome; Middle Aged; Olanzapine; Paliperidone Palmitate; Psychiatric Status Rating Scales; Pyrimidines; Schizophrenia; Triglycerides; Waist Circumference

This study aimed to compare the effects of the two most commonly prescribed atypical antipsychotics, olanzapine and risperidone, on fasting blood sugar and serum lipid profile of the recipients.. A randomised, comparative, open clinical study was conducted on 60 schizophrenic patients. The patients were divided into two groups, one receiving olanzapine and the other receiving risperidone. The patients were assessed for changes in fasting blood sugar and serum lipid profile (triglycerides [TG], high-density lipoprotein [HDL], low-density lipoprotein [LDL], very-low-density lipoprotein [VLDL] and total cholesterol) eight weeks after starting treatment. The number of patients positive for fasting blood sugar and lipid profile criteria of metabolic syndrome was calculated by applying the modified National Cholesterol Education Programme Adult Treatment Panel III guidelines (NCEP ATP III) criteria at eight weeks.. Patients treated with olanzapine showed a highly significant increase in the observed parameters, whereas those treated with risperidone showed a significant increase in fasting blood sugar, HDL and LDL levels, and a highly significant increase in other parameters. Intergroup comparison was insignificant except for TG, VLDL and total cholesterol levels. More men as compared to women fulfilled the NCEP ATP III criteria for metabolic syndrome in both groups.. Olanzapine has a higher propensity to cause derangement of some parameters of lipid profile than risperidone. These parameters include TG, VLDL and total cholesterol levels.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Cholesterol; Female; Humans; Lipids; Lipoproteins, HDL; Lipoproteins, LDL; Lipoproteins, VLDL; Male; Metabolic Syndrome; Olanzapine; Reproducibility of Results; Risperidone; Schizophrenia; Triglycerides

The second generation antipsychotic drugs, such as risperidone, olanzapine, and quetiapine, are effective in treating patients with schizophrenia and have been considered as the first line therapy. Recently, increasing attention has been drawn to the potential diabetogenic effect of these novel antipsychotics. The goal of this study was to evaluate the effect of metformin treatment on the olanzapine-induced metabolic disturbance in schizophrenic patients. Twenty-four schizophrenic subjects who had received olanzapine treatment at least 3 months were assigned to the therapy with metformin 1500 mg/day for 8 weeks. The metabolic parameters were quantitatively assessed at baseline, weeks 2, 4, and 8 by using the intravenous glucose tolerance test. After an 8-week treatment with metformin, the body weight, fasting levels of glucose, triglyceride, and insulin, insulin secretion, and insulin resistance significantly decreased. Half of study subjects with metabolic syndrome obtained improvement after the metformin trial. Subjects' psychopathological condition remained unchanged during the study period. The olanzapine-induced metabolic disturbance could be reversed after 8-week metformin treatment. Based on the results of this study, we hypothesize that metformin could modulate the effect of olanzapine-induced metabolic disturbance.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Weight; Female; Glucose; Glucose Tolerance Test; Humans; Hypoglycemic Agents; Lipids; Male; Metabolic Diseases; Metabolic Syndrome; Metformin; Middle Aged; Olanzapine; Prospective Studies; Schizophrenia; Sex Characteristics

Metformin (850-1700 mg) plus sibutramine (10-20 mg, n=13) or placebo (n=15) was administered for 12 weeks in olanzapine-treated chronic schizophrenia patients. Weight loss was similar in both groups: -2.8+/-3.2 kg vs. -1.4+/-2.6 kg. Except for preventing a triglyceride increase, the drug combination lacked efficacy for metabolic control in this clinical population.

Topics: Adult; Antipsychotic Agents; Appetite Depressants; Benzodiazepines; Body Mass Index; Chronic Disease; Cyclobutanes; Double-Blind Method; Female; Humans; Hypoglycemic Agents; Male; Metabolic Syndrome; Metformin; Middle Aged; Obesity; Olanzapine; Pilot Projects; Placebos; Schizophrenia; Schizophrenic Psychology; Waist-Hip Ratio; Weight Gain; Weight Loss

In this study, the Authors assessed some insulin counter-regulatory factors, fibrinogen and C-reactive protein after olanzapine administration, and the effect of metformin on these variables, 37 patients with chronic schizophrenia were given olanzapine (10 mg/day for 14 weeks). Nineteen patients received metformin (850-2550 mg/day) and 18 received placebo in a randomized, double-blind protocol. The following variables were quantified before and after olanzapine: cortisol, leptin, tumor necrosis factor-alpha, glucagon, growth hormone, fibrinogen and C-reactive protein. Results were correlated with the changes in body weight and the insulin resistance index. We have reported elsewhere that metformin did not prevent olanzapine-induced weight gain, and the insulin resistance index significantly decreased after metformin and placebo; Baptista T, et al. Can J Psychiatry 2006; 51: 192-196. Cortisol, tumor necrosis factor-alpha and fibrinogen levels significantly decreased in both groups. Glucagon significantly increased after metformin (P=0.03). Leptin tended to increase after placebo (P=0.1) and displayed a small nonsignificant reduction after metformin. The C-reactive protein did not change significantly in any group. Contrarily to most published studies, olanzapine was associated with decreased insulin resistance. Decrements in cortisol, fibrinogen and tumor necrosis factor-alpha levels point to an improvement in the metabolic profile. The trend for leptin to increase after placebo, but not after metformin in spite of similar weight gain suggests a beneficial effect of this antidiabetic agent.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Blood Glucose; C-Reactive Protein; Double-Blind Method; Female; Fibrinogen; Glucagon; Human Growth Hormone; Humans; Hydrocortisone; Hypoglycemic Agents; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Metformin; Middle Aged; Olanzapine; Schizophrenia; Sex Factors; Treatment Outcome; Tumor Necrosis Factor-alpha

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Double-Blind Method; Female; Humans; Incidence; India; Metabolic Syndrome; Olanzapine; Prospective Studies; Risperidone; Schizophrenia; Sex Factors; Treatment Outcome

Glucose and lipid metabolism dysfunction is a significant side effect associated with antipsychotics. Although there are many studies about the linkages between drugs and metabolic dysfunction, most of these studies have compared the effects of two antipsychotics on only one metabolic measure: either glucose or lipid metabolism.. The present study aimed to investigate the effects of clozapine, olanzapine, risperidone, and sulpiride on glucose and lipid metabolism in first-episode schizophrenia.. One hundred twelve schizophrenics were assigned randomly to receive clozapine, olanzapine, risperidone, or sulpiride for 8 weeks. Planned assessments included body mass index (BMI), waist-to-hip ratio, fasting glucose, insulin, C-peptide, insulin resistance index (IRI), cholesterol, and triglyceride. All measures were collected at baseline and at the end of the 8-week treatment.. After treatment, insulin, C-peptide, and IRI were significantly increased in the four groups, but not fasting glucose levels. Cholesterol and triglyceride levels were significantly increased in the clozapine and olanzapine groups. Patients treated with clozapine and olanzapine had higher fasting insulin, C-peptide, and IRI levels than those treated with risperidone and sulpiride. Among the four antipsychotics, the increases of mean BMI from high to low were as follows: clozapine, olanzapine, sulpiride, and risperidone.. This study confirmed that the four antipsychotic drugs were associated with an increase of insulin, C-peptide, and IRI. It was found that clozapine and olanzapine were associated with an increase in cholesterol and triglyceride levels. The effects of clozapine and olanzapine on the glucose and lipid metabolism outweighed those of risperidone and sulpiride.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Mass Index; C-Peptide; Cholesterol; Clozapine; Female; Homeostasis; Humans; Insulin; Insulin Resistance; Lipid Metabolism; Male; Metabolic Syndrome; Olanzapine; Prospective Studies; Risperidone; Schizophrenia; Sulpiride; Triglycerides; Waist-Hip Ratio

A major contributor to mortality inpatients with schizophrenia or schizoaffective disorder is cardiovascular disease, an important risk factor for which is the cluster of clinical abnormalities that define the metabolic syndrome (eg, abdominal/visceral obesity, hypertriglyceridemia, impaired glucose tolerance).. The aim of this article was to examine the effects of switching from the antipsychotic olanzapine to risperidone on the prevalence of the metabolic syndrome in high-risk overweight or obese patients with schizophrenia or schizoaffective disorder.. This post hoc analysis was based on data from a previous 2-phase, 20-week, multicenter (19 US sites), rater-blinded, open-label study. High-risk overweight or obese (body mass index [BMI], >26 kg/m(2)) patients aged 18 to 65 years with schizophrenia or schizoaffective disorder whose treatment was switched from olanzapine to risperidone were enrolled. Patients who entered the phase 1 switch from olanzapine to risperidone (6 weeks) and the phase 2 extension (14 weeks) were included in the assessment. The primary end point was the difference from baseline in the prevalence of the metabolic syndrome at week 20, determined using measurements of weight, BMI, waist circumference, and systolic and diastolic blood pressure (SBP/DBP).. Baseline assessments for the metabolic syndrome were available from 121 of 123 patients recruited for phase 1 of the study (61 men, 60 women; mean [SD] age, 41.1 [10.2] years; mean [SD] BMI, 33.9 [6.9] kg/m(2)); 71 patients entered phase 2 (29 men, 42 women; mean [SD] age, 40.2 [10.3] years; mean [SD] BMI, 35.1 [7.3] kg/m(2)), of whom 39 (54.9%) ere diagnosed with schizophrenia, and 32 (45.1%) with schizoaffective disorder. The metabolic syndrome was identified in 63 (52.1%) patients at study entry. In the 71 patients with data available from baseline and week 20 (using the last observation carried forward method), the prevalence of the metabolic syndrome was reduced from 38 (53.5%) patients at baseline to 26 (36.6%) at study end (McNemar chi(2) = 8.0, P < 0.005). Significant improvements at study end were seen in mean weight (P = 0.031), BMI (P = 0.002), waist circumference (P = 0.003), SBP (P = 0.006), and DBP (P = 0.010). There was no significant difference in the reduction in the prevalence of the metabolic syndrome between patients who did or did not receive the behavioral therapy for weight loss.. In this post hoc analysis of switching from the antipsychotic olanzapine to risperidone on the prevalence of the metabolic syndrome in high-risk overweight or obese patients with schizophrenia or schizoaffective disorder, the metabolic syndrome was highly prevalent at baseline. Switching from olanza- pine to risperidone was associated with a significant reduction in this prevalence.

Topics: Adult; Antipsychotic Agents; Behavior Therapy; Benzodiazepines; Blood Pressure; Body Mass Index; Body Weight; Female; Humans; Male; Metabolic Syndrome; Obesity; Olanzapine; Prevalence; Psychotic Disorders; Risperidone; Schizophrenia; Systole; United States; Waist-Hip Ratio

Limited randomized, controlled trial data exist on possible differences between atypical antipsychotics in efficacy, overall tolerability, and important indices of health status. The authors compared the efficacy and tolerability of ziprasidone and olanzapine in the treatment of acutely ill inpatients with schizophrenia or schizoaffective disorder.. In this 6-week, multicenter, double-blind, parallel-design, flexible-dose trial, patients were randomly assigned to receive ziprasidone (N=136) or olanzapine (N=133). Primary efficacy measures were improvement in Brief Psychiatric Rating Scale and Clinical Global Impression (CGI) severity scale scores; secondary measures were scores on the CGI improvement scale, Positive and Negative Syndrome Scale, and Calgary Depression Scale for Schizophrenia. Tolerability assessments included fasting lipid profiles, fasting glucose and insulin measurements, electrocardiography, and monitoring of vital signs and body weight.. The overall mean daily doses were 129.9 mg (SD=27.3) for ziprasidone and 11.3 mg (SD=2.8) for olanzapine. Both antipsychotics were efficacious in improving symptoms and global illness severity. The two treatment groups did not differ significantly in primary or secondary efficacy measures at endpoint or in by-visit analysis. Both agents were well tolerated. Body weight, total cholesterol, triglycerides, and low-density lipoprotein cholesterol significantly increased with olanzapine but not with ziprasidone; all between-group comparisons of these variables were significant and favored ziprasidone. Olanzapine, but not ziprasidone, was associated with significant increases in fasting insulin level. No patient in either group exhibited a corrected QT interval >/=500 msec.. During 6 weeks' treatment, ziprasidone and olanzapine demonstrated comparable antipsychotic efficacy. Differences favoring ziprasidone were observed in metabolic parameters.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Lorazepam; Male; Metabolic Syndrome; Middle Aged; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Thiazoles; Treatment Outcome; Weight Gain

Psychotropic drugs may be associated with metabolic disorders, often but not only triggered by weight gain. Disorders include dysglycemia and diabetes, atherogenic dyslipidemia and metabolic syndrome. Overall, metabolic risk is lower with antidepressants than with antipsychotics. Among antidepressants, metabolic disorders may occur with both selective serotonin reuptake inhibitors and tricyclics, but with some between-molecule differences in each pharmacological family. Among antipsychotics, the risk is higher with second-generation (atypical) than first-generation agents. Higher risk was reported with clozapine and olanzapine, and lower risk with risperidone and aripiprazole. Weight gain is associated with increased insulin resistance, but impaired insulin secretion was also reported with clozapine and olanzapine. Metabolic disorders may be attenuated by the medication withdrawal and replacement by another safer drug. Besides deleterious effects of medications, the psychiatric population is also exposed to bad lifestyle habits (unhealthy diet and sedentary life), which also increase the risk of metabolic disorders. Management should first reinforce lifestyle measures. If this proves insufficient, specific drugs may be considered to tackle the metabolic disorder on a strategy similar to that applied in the general population.

Topics: Clozapine; Humans; Metabolic Diseases; Metabolic Syndrome; Olanzapine; Psychotropic Drugs

Atypical antipsychotics such as risperidone cause drug-induced metabolic syndrome. However, the underlying mechanisms remain largely unknown. Here, we report a new mouse model that reliably reproduces risperidone-induced weight gain, adiposity, and glucose intolerance. We found that risperidone treatment acutely altered energy balance in C57BL/6 mice and that hyperphagia accounted for most of the weight gain. Transcriptomic analyses in the hypothalamus of risperidone-fed mice revealed that risperidone treatment reduced the expression of Mc4r. Furthermore, Mc4r in Sim1 neurons was necessary for risperidone-induced hyperphagia and weight gain. Moreover, we found that the same pathway underlies the obesogenic effect of olanzapine-another commonly prescribed antipsychotic drug. Remarkably, whole-cell patch-clamp recording demonstrated that risperidone acutely inhibited the activity of hypothalamic Mc4r neurons via the opening of a postsynaptic potassium conductance. Finally, we showed that treatment with setmelanotide, an MC4R-specific agonist, mitigated hyperphagia and obesity in both risperidone- and olanzapine-fed mice.

Topics: alpha-MSH; Animals; Antipsychotic Agents; Female; Hyperphagia; Hypothalamus; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Models, Animal; Neurons; Obesity; Olanzapine; Potassium; Receptor, Melanocortin, Type 4; Risperidone; Synaptic Potentials; Transcriptome; Weight Gain

Olanzapine (OLZ) is one of the most effective atypical antipsychotics but is associated with severe metabolic side effects, in which the gut microbiota plays an important role. Akkermansia muciniphila (A. muciniphila; Akk), a Gram-negative anaerobic bacterium in the intestine, can potentially improve metabolic syndrome.. This study investigated the effect and underlying mechanisms of an A. muciniphila subtype (A. muciniphila. C57BL/6 female mice were fed a high-fat diet to induce obesity or normal chow for 8 weeks before OLZ treatment for 16 weeks. During the treatment period, mice in each group were orally administrated A. muciniphila. A. muciniphila

Topics: Akkermansia; Animals; Antipsychotic Agents; Base Composition; Female; Glucose; Homeostasis; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Olanzapine; Phylogeny; Probiotics; RNA, Ribosomal, 16S; Sequence Analysis, DNA

Schizophrenia (Sz) patients, especially treated with atypical antipsychotics, are at high risk of the development of metabolic syndrome that increases morbidity and mortality and impairs compliance with treatment. Mechanism of the high association of metabolic syndrome with the use of atypical antipsychotics is not clear. Literature and our data suggest that chronic inflammation- or stress-induced dysregulation of the peripheral down-stream kynurenine (Kyn) metabolism, shared by both Sz and metabolic syndrome, contributes to the development of metabolic syndrome in Sz patients treated with atypical antipsychotics. Correction of dysregulation of the peripheral down-stream metabolism of Kyn would prevent/treat metabolic syndrome. This is a pre-clinical trial of the effect of benserazide (BRZ), an inhibitor of the key enzymes of Kyn metabolism, on olanzapine-induced mouse model of metabolic syndrome. Olanzapine is one of the most effective atypical antipsychotics but has high potential to induce metabolic syndrome. Olanzapine (4 mg/kg, p.o) and/or BRZ (100 mg/day, p.o.) were administered to 6-week-old C57Bl/6 female mice, 5 days/week, for 10 weeks. The study was approved by the Tufts Medical Center Institutional Animal Care and Use Committee. BRZ attenuated olanzapine-induced excessive weight gain, impairment of glucose tolerance, and elevation of plasma cholesterol and triglycerides. Present results suggest that peripheral down-stream Kyn metabolism is a new target for prevention/treatment of olanzapine-induced metabolic syndrome. BRZ has a high translational potential as medication already approved for human use.

Topics: Animals; Antipsychotic Agents; Benserazide; Dyslipidemias; Female; Insulin Resistance; Kynurenine; Metabolic Syndrome; Mice, Inbred C57BL; Obesity; Olanzapine; Weight Gain

Ghrelin is a peptide hormone that mediates glucose homeostasis and lipid metabolism. Acylated ghrelin (AG) and desacylated ghrelin (DAG) are the two main forms of ghrelin, which have opposing roles in energy homeostasis. The AG/DAG ratio has been proposed to be associated with metabolic syndrome (MetS) in the general population. This study compared the relationships between MetS and ghrelin parameters in patients with schizophrenia.. Patients diagnosed with schizophrenia and under olanzapine monotherapy were recruited. Fasting blood samples were collected for the analyses of metabolic and ghrelin parameters. The serum levels of total ghrelin and AG were measured by enzyme-linked immunosorbent assay kits. DAG level was calculated by subtracting the AG level from the total ghrelin level.. Our results revealed that lower AG/DAG ratios were associated with better metabolic profiles in olanzapine-treated patients with schizophrenia. These observations suggest that the balance between AG and DAG plays a crucial role in the metabolic homeostasis among patients with schizophrenia.

Topics: Acylation; Adult; Case-Control Studies; Female; Ghrelin; Humans; Male; Metabolic Syndrome; Olanzapine; Schizophrenia; Sex Factors

Olanzapine has been used for the treatment of schizophrenia and other mental disorders. However, it is associated with serious weight gain and other metabolic side-effects. The antagonistic affinity of olanzapine to muscarinic M3 receptors has been evidenced as one of the main contributors for its weight gain and other metabolic side-effects. Therefore, this study investigated whether the co-treatment of cevimeline (a M3 receptor agonist) could prevent the metabolic side-effects associated with olanzapine medication. Female Sprague Dawley rats were treated orally with olanzapine (2 mg/kg, t.i.d.) and/or cevimeline at 3 dosages (3, 6, 9 mg/kg, t.i.d.), or vehicle for two weeks. Weight gain and food/water intake were measured throughout the drug treatment period. Intraperitoneal glucose tolerance tests and open field tests were conducted. Olanzapine-treated rats demonstrated significantly elevated body weight gain, food intake, feeding efficiency, total white fat mass, liver mass, and plasma triglyceride levels, which could be partly reversed by the co-treatment with cevimeline in a dosage-dependent manner. In general, the body weight gain can only be reversed by the co-treatment of 9 mg/kg cevimeline. The cevimeline co-treatment decreased plasma triglyceride and glucose levels compared with olanzapine only treatment. The results suggested a dosage-dependent effect of cevimeline in ameliorating olanzapine-induced weight gain and metabolic side-effects, which supports further clinical trials using cevimeline to control weight gain and metabolic side-effects caused by antipsychotic medications.

Topics: Adipose Tissue; Adiposity; Animals; Behavior, Animal; Blood Glucose; Dose-Response Relationship, Drug; Drug Interactions; Eating; Female; Locomotion; Metabolic Syndrome; Olanzapine; Open Field Test; Quinuclidines; Rats; Rats, Sprague-Dawley; Receptor, Muscarinic M3; Thiophenes; Treatment Outcome; Triglycerides; Weight Gain

In this study, we hypothesized that fatty acid desaturase-1 (FADS1) and fatty acid desaturase-2 (FADS2) may mediate metabolic syndrome (MetS) in patients receiving olanzapine monotherapy. 216 schizophrenia patients were recruited. There is a significant difference between the patients with or without MetS in term of the expression of FADS1 mRNA (F = 4.58, P = 0.03), but not FADS2 mRNA (F = 1.29, P = 0.26). We observed a positive association between FADS1 mRNA and high-density lipoprotein cholesterol (P = 0.04), and a negative association between FADS1 mRNA and systolic blood pressure (P = 0.04). Our findings implied that FADS1 may be an important genetic modifier that can regulate olanzapine-associated metabolic disturbance.

Topics: Delta-5 Fatty Acid Desaturase; Fatty Acid Desaturases; Humans; Metabolic Syndrome; Olanzapine; Polymorphism, Single Nucleotide; Schizophrenia

To elucidate the protective effect of berberine on olanzapine induced-metabolic syndrome.. This prospective experimental study involved thirty Sprague-Dawley male rats which were divided into three groups. Group A (n=10): Rats treated with distilled water, Group B (n=10): Rats treated with olanzapine, Group C (n=10): Rats treated with olanzapine plus berberine. The duration of the study was 8 weeks, baseline and follow up data were evaluated. Fasting blood glucose(FBG) total cholesterol (TC), triglyceride (TG) and high-density lipoprotein (HDL), Low density lipoprotein (LDL), atherogenic index of plasma (AI), fasting serum insulin level, insulin resistance, β- cell function and insulin sensitivity were evaluated.SPSS 20.. Olanzepine led to significant deterioration in gluco-metabolic profile compared with control P<0.01. Olanzapine plus berberine improved body weight, FBG, FSI, HOMA-IR and QUICKI compared with olanzapine P=0.0001.. Berberine attenuates olanzapine induced-metabolic via amelioration of gluco-lipid disturbances.

Topics: Animals; Berberine; Biomarkers; Insulin Resistance; Male; Metabolic Syndrome; Olanzapine; Prospective Studies; Rats; Rats, Sprague-Dawley; Weight Gain

Olanzapine is a second-generation anti-psychotic drug used to prevent neuroinflammation in patients with schizophrenia. However, the long-term administration of olanzapine leads to insulin resistance (IR); the mechanisms of this effect remains poorly understood. Using cellular and rodent models of IR induced by olanzapine, we found that chronic olanzapine treatment induces differential inflammatory cytokine reactions in peripheral adipose and the central nervous system. Long-term treatment of olanzapine caused metabolic symptoms, including IR, by markedly elevating the plasma levels of pro-inflammatory cytokines, including IL-1ß, IL-6, IL-8 and TNFα; these findings are consistent with observations from schizophrenia patients chronically treated with olanzapine. Our observations of differential inflammatory cytokine responses in white adipose tissues from the prefrontal cortex in the brain indicated cell type-specific effects of the drug. These cytokines induced IR by activating NF-kB through the suppression of IkBα. Functional blockade of the components p50/p65 of NF-kB rescued olanzapine-induced IR in NIH-3T3 L1-derived adipocytes. Our findings demonstrate that olanzapine induces inflammatory cytokine reactions in peripheral tissues without adversely affecting the central nervous system and suggest that chronic olanzapine treatment of schizophrenia patients may cause inflammation-mediated IR with minimal or no adverse effects in the brain.

Topics: 3T3-L1 Cells; Adipocytes; Adult; Animals; Antipsychotic Agents; Blood Glucose; Cytokines; Disease Models, Animal; Duration of Therapy; Female; Glucose Transporter Type 4; Humans; Inflammation Mediators; Insulin Resistance; Male; Metabolic Syndrome; Mice; Models, Biological; NF-kappa B; Olanzapine; Rats; Schizophrenia; Young Adult

Pulmonary hypertension (PH) due to left heart disease (LHD), or group 2 PH, is the most prevalent form of PH worldwide. PH due to LHD is often associated with metabolic syndrome (MetS). In 12% to 13% of cases, patients with PH due to LHD display vascular remodeling of pulmonary arteries (PAs) associated with poor prognosis. Unfortunately, the underlying mechanisms remain unknown; PH-targeted therapies for this group are nonexistent, and the development of a new preclinical model is crucial. Among the numerous pathways dysregulated in MetS, inflammation plays also a critical role in both PH and vascular remodeling.. We hypothesized that MetS and inflammation may trigger the development of vascular remodeling in group 2 PH.. Using supracoronary aortic banding, we induced diastolic dysfunction in rats. Then we induced MetS by a combination of high-fat diet and olanzapine treatment. We used metformin treatment and anti-IL-6 (interleukin-6) antibodies to inhibit the IL-6 pathway. Compared with sham conditions, only supracoronary aortic banding+MetS rats developed precapillary PH, as measured by both echocardiography and right/left heart catheterization. PH in supracoronary aortic banding+MetS was associated with macrophage accumulation and increased IL-6 production in lung. PH was also associated with STAT3 (signal transducer and activator of transcription 3) activation and increased proliferation of PA smooth muscle cells, which contributes to remodeling of distal PA. We reported macrophage accumulation, increased IL-6 levels, and STAT3 activation in the lung of group 2 PH patients. In vitro, IL-6 activates STAT3 and induces human PA smooth muscle cell proliferation. Metformin treatment decreased inflammation, IL-6 levels, STAT3 activation, and human PA smooth muscle cell proliferation. In vivo, in the supracoronary aortic banding+MetS animals, reducing IL-6, either by anti-IL-6 antibody or metformin treatment, reversed pulmonary vascular remodeling and improve PH due to LHD.. We developed a new preclinical model of group 2 PH by combining MetS with LHD. We showed that MetS exacerbates group 2 PH. We provided evidence for the importance of the IL-6-STAT3 pathway in our experimental model of group 2 PH and human patients.

Topics: Animals; Cells, Cultured; Diet, High-Fat; Disease Models, Animal; Humans; Hypertension, Pulmonary; Interleukin-6; Macrophages; Male; Metabolic Syndrome; Olanzapine; Pulmonary Artery; Rats; Rats, Wistar; Vascular Remodeling; Ventricular Dysfunction

There is accumulating evidence indicating that long-term treatment with second-generation antipsychotics (SGAs) results in metabolic syndrome (MetS) and cognitive impairment. This evidence suggests an intrinsic link between antipsychotic-induced MetS and cognitive dysfunction in schizophrenia patients. Olanzapine is a commonly prescribed SGA with a significantly higher MetS risk than that of most antipsychotics. In this study, we hypothesized that olanzapine-induced MetS may exacerbate cognitive dysfunction in patients with schizophrenia.. A sample of 216 schizophrenia patients receiving long-term olanzapine monotherapy were divided into two groups, MetS and non-MetS, based on the diagnostic criteria of the National Cholesterol Education Program's Adult Treatment Panel III. We also recruited 72 healthy individuals for a control group. Cognitive function was evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Plasma brain-derived neurotrophic factor (BDNF) and tumor necrosis factor-alpha (TNF-alpha) were measured by an enzyme-linked immunosorbent assay for 108 patients and 47 controls.. Among the 216 schizophrenia patients receiving olanzapine monotherapy, MetS was found in 95/216 (44%). Patients with MetS had more negative symptoms, higher total scores in PANSS (Ps<0.05) and lower immediate memory, attention, delayed memory and total scores in RBANS (Ps<0.01). Stepwise multivariate linear regression analysis revealed that increased glucose was the independent risk factor for cognitive dysfunction (t=-2.57, P=0.01). Patients with MetS had significantly lower BDNF (F=6.49, P=0.012) and higher TNF-alpha (F=5.08, P=0.026) levels than those without MetS. There was a negative correlation between the BDNF and TNF-alpha levels in the patients (r=-0.196, P=0.042).. Our findings provide evidence suggesting that the metabolic adverse effects of olanzapine may aggravate cognitive dysfunction in patients with schizophrenia through an interaction between BDNF and TNF-alpha.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Brain-Derived Neurotrophic Factor; Case-Control Studies; Cognitive Dysfunction; Cross-Sectional Studies; Female; Humans; Male; Metabolic Syndrome; Olanzapine; Schizophrenia; Treatment Outcome; Tumor Necrosis Factor-alpha; Young Adult

Atypical antipsychotics particularly olanzapine are associated with obesity and serious metabolic disturbances. As green tea (Camellia sinensis) is generally associated with beneficial effects on obesity and other metabolic disturbances, this study was undertaken to evaluate the effect of green tea aqueous extract (GTAE) on olanzapine induced weight gain and metabolic abnormalities in rats. Male Wistar rats were divided into eight groups: control, olanzapine (5mg/kg/day, IP.), GTAE (25, 50 and 100mg/kg/day, IP.) plus olanzapine and GTAE (25, 50 and 100mg/kg/day, IP.). Treatments were continued for 11 days. Body weight gain, average food and water intake were measured during the experiment. Plasma lipid, glucose and leptin levels, mean systolic blood pressure and total locomotion were evaluated at the end of experiment. Olanzapine induced significant weight gain at the end of treatment (10.38% of body weight) when compared to control (3.13% of body weight) in male Wistar rats. Average food and water intake were increased by olanzapine treatment. 11days olanzapine administration led to hyperleptinemia, hyperglycemia and dyslipidemia. Olanzapine also increased mean systolic blood pressure and decreased total locomotion. GTAE decreased significantly body weight gain and average food and water intake, improved the changes in lipid profile as well as fasting blood glucose, and finally decreased hyperleptinemia and hypertension induced by olanzapine. Results of this study demonstrated that GTAE could exert protective effects against olanzapine induced obesity partially due to its lowering effect on leptin. GTAE improved other metabolic abnormalities including dyslipidemia, hyperglycemia and hypertension induced by olanzapine in rats.

Topics: Animals; Benzodiazepines; Blood Glucose; Blood Pressure; Body Weight; Drinking; Feeding Behavior; Leptin; Lipids; Male; Metabolic Syndrome; Motor Activity; Olanzapine; Polyphenols; Protective Agents; Rats, Wistar; Systole; Tea; Triglycerides

The adverse metabolic risks associated with second generation antipsychotics (SGAs) are well known, and likely contribute to the high rate of premature mortality due to cardiovascular disease in schizophrenia. Female schizophrenia patients appear to be diagnosed with metabolic diseases at higher rates than males, which may reflect disparate adverse responses to SGAs. However, the relationship between sex, metabolic risk, and drug use is less developed. We aimed to explore this relationship further by identifying rates of metabolic disease in community dwelling schizophrenia patients by sex and SGA risk. Schizophrenia participants (N = 287, 40.4% female) were included in this analysis. Oneway-ANOVA and Fisher's Exact Test were used to compare groups, as appropriate, and Cohen's d was employed to estimate the effect size of sex. In the group as a whole, the rate of metabolic syndrome was higher than previously reported, but did not differ by sex. For females, greater metabolic disturbances across all medication risk groups were seen in BMI and waist circumference (p < 0.005) but most commonly in those receiving high risk medication (clozapine or olanzapine). Additionally, the number of participants receiving medications for these metabolic disturbances was extremely low (<30%). These results suggest that female schizophrenia patients taking clozapine or olanzapine represent a group at uniquely high risk for metabolic dysfunction and future adverse cardiovascular outcomes, and warrant close monitoring by clinicians to prevent worsening of metabolic risk through proper monitoring and interventions.

Topics: Adult; Antipsychotic Agents; Body Mass Index; Clozapine; Cross-Sectional Studies; Female; Humans; Male; Metabolic Syndrome; Middle Aged; Olanzapine; Risk Factors; Schizophrenia; Sex Factors; Waist Circumference

The use of atypical antipsychotics (AAPs) in the treatment of schizophrenia has been relevant because of the high prevalence of metabolic syndrome (MetS). The sterol-regulatory element-binding protein (SREBP) pathway may contribute to the underlying pathophysiology of AAP-induced metabolic adverse effects. We explored the association between the variants of the sterol-regulatory element-binding transcription factor-1 (SREBF1) gene and the SREBP cleavage-activation protein (SCAP) gene with AAP-induced MetS in a genetic case-control study.. Eleven single nucleotide polymorphisms (SNPs) of SREBF1 and five of SCAP were genotyped in a Han Chinese population in Beijing, China: a sample of 722 schizophrenia patients on monotherapy with AAPs (clozapine, olanzapine or risperidone). Metabolic parameters were collected and evaluated for MetS criteria.. The rs11654081 T-allele of the SREBF1 gene was significantly associated with an increased risk for MetS after correction (P = 0.019, odds ratio, OR =2.56, 95% confidence interval, CI: 1.4 4-4.54). The rs11654081-TT genotype appeared more frequently in MetS than in non-MetS after correction (P = 0.026, OR =2.37, 95% CI: 1.3 6-4.12). SCAP polymorphisms with drug-induced MetS were negative in this study.. The genetic polymorphisms of SREBF1 could play a role in the mechanism for interindividual variation of AAP-induced MetS.

Topics: Adult; Alleles; Antipsychotic Agents; Benzodiazepines; Case-Control Studies; China; Clozapine; Female; Genotype; Humans; Intracellular Signaling Peptides and Proteins; Linkage Disequilibrium; Logistic Models; Male; Membrane Proteins; Metabolic Syndrome; Middle Aged; Olanzapine; Polymorphism, Single Nucleotide; Risperidone; Schizophrenia; Sterol Regulatory Element Binding Protein 1

Individuals with a diagnosis of schizophrenia have a reduced life expectancy compared with the general population and cardiovascular disease is the major contributor to this early mortality. The use of second-generation antipsychotic (SGA) medications is associated with significant weight gain and metabolic side effects; however, there is limited knowledge in certain diagnostic groups, specifically early-onset schizophrenia (EOS). This study aimed to investigate the metabolic side effects of SGAs, specifically olanzapine, risperidone and quetiapine, in a cohort of drug-naïve children and adolescents with first-episode EOS.. Body mass index (BMI), serum cholesterol and triglycerides were measured at baseline and a median of 7 months of follow up in drug-naïve children and adolescents with EOS.. A total of 49 children and adolescents received a diagnosis of first-episode EOS and we had complete follow-up data for 74% (N = 36). A significant increase in BMI, serum triglycerides and cholesterol was observed in the unselected cohort after commencement of SGAs. One-third of children and adolescents had abnormal serum triglycerides and cholesterol; however, a dose-response was not demonstrated. Olanzapine and quetiapine had a greater increase in serum triglycerides.. In addition to highlighting the need for routine screening for metabolic side effects in EOS, interventions to prevent and treat obesity and the metabolic syndrome are indicated.

Topics: Adolescent; Age of Onset; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Cholesterol; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Male; Metabolic Syndrome; Olanzapine; Quetiapine Fumarate; Risperidone; Schizophrenia; Triglycerides; Victoria

Alterations in one-carbon metabolism (OCM) have been repeatedly reported in schizophrenia. However, there is a scarcity of studies addressing the effects of antipsychotics on selected OCM markers in schizophrenia and provided results are inconsistent.. We recruited 39 first-episode schizophrenia (FES) patients and determined serum profile of total homocysteine (tHcy), folate, vitamin B12, lipoproteins and glucose at baseline and after 12 weeks of treatment with second-generation antipsychotics (SGA) including olanzapine and risperidone in monotherapy.. After 12 weeks of treatment, all patients had significantly higher body mass index (BMI), serum levels of total cholesterol (TC), low-density lipoproteins (LDL), triglycerides (TG) and tHcy together with significantly lower levels of folate and vitamin B12. The analysis of differences between SGA revealed the same biochemical alterations in patients treated with olanzapine as in the whole group, while those receiving risperidone had no statistically significant changes in serum folate, vitamin B12 and TG. There was a significantly higher increase in BMI and TC in patients treated with olanzapine in comparison with those treated with risperidone. Patients receiving olanzapine had a higher decrease in vitamin B12 than those assigned to the treatment with risperidone. Changes in folate, vitamin B12, tHcy and TC levels were significant only in males, even after Bonferroni correction. Multiple regression analysis revealed that changes in tHcy levels are associated with gender and baseline metabolic parameters (BMI, glucose, TC, LDL and HDL) but not with selected SGA.. These results indicate that SGA may influence OCM, especially in first-episode schizophrenia (FES) males.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Mass Index; Carbon; Cholesterol; Female; Folic Acid; Homocysteine; Humans; Lipid Metabolism; Male; Metabolic Syndrome; Olanzapine; Risperidone; Schizophrenia; Sex Factors; Triglycerides; Vitamin B 12; Young Adult

The use of atypical antipsychotics (AAPs) is associated with increasing the risk of the metabolic syndrome (MetS), which is an important risk factor for cardiovascular disease and diabetes. Two insulin-induced gene (INSIG) isoforms, designated INSIG-1 and INSIG-2 encode two proteins that mediate feedback control of lipid metabolism. In this genetic case-control study, we investigated whether the common variants in INSIG1 and INSIG2 genes were associated with MetS in schizophrenic patients treated with atypical antipsychctics. The study included 456 schizophrenia patients treated with clozapine (n=171), olanzapine (n=91) and risperidone (n=194), for an average of 45.5±27.6 months. The prevalence of MetS among all subjects was 22.8% (104/456). Two single-nucleotide polymorphisms (SNPs) of the INSIG1 gene and seven SNPs of the INSIG2 gene were chosen as haplotype-tagging SNPs. In single-marker-based analysis, the INSIG2 rs11123469-C homozygous genotype was found to be more frequent in the patients with MetS than those without MetS (P=0.001). In addition, haplotype analysis showed that the C-C-C haplotype of rs11123469-rs10185316- rs1559509 of the INSIG2 gene significantly increased the risk of MetS (P=0.0023). No significant associations were found between polymorphisms of INSIG1 gene and MetS, however, INSIG1 and INSIG2 interactions were found in the significant 3-locus and 4-locus gene-gene interaction models (P=0.003 and 0.012, respectively). The results suggest that the INSIG2 gene may be associated with MetS in patients treated with AAPs independently or in an interactive manner with INSIG1.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Case-Control Studies; Cross-Sectional Studies; Epistasis, Genetic; Female; Humans; Intracellular Signaling Peptides and Proteins; Male; Membrane Proteins; Metabolic Syndrome; Middle Aged; Olanzapine; Polymorphism, Single Nucleotide; Risperidone; Schizophrenia; Treatment Outcome

Retinol-binding protein 4 (RBP4) has been shown to be associated with insulin resistance (IR), metabolic indices and metabolic syndrome (MetS) in various patient populations and in obesity. We investigated the association between metabolic parameters, IR and RBP4 during olanzapine therapy.. A prospective study.. Thirty-seven participants with psychiatric disorder who were atypical antipsychotic naive and newly initiated on olanzapine were assessed.. Fasting RBP4, anthropometric and metabolic variables were measured before and after 3 months of olanzapine therapy.. Participants who developed MetS showed higher RBP4 levels compared with those without MetS, although not significant (P = 0·053). The variation in RBP4 level was correlated with changes in systolic blood pressure (r = 0·423, P = 0·009), diastolic blood pressure (r = 0·390, P = 0·017), total cholesterol (r = 0·446, P = 0·006) and low-density lipoprotein (LDL) (r = 0·407, P = 0·012). Multiple linear regression analysis illustrated that end-point log insulin level was the most significant independent predictor of final log RBP4 levels (standardized ß = 0·353, P = 0·024).. Our results suggest that RBP4 levels might be associated with at least some olanzapine-induced metabolic abnormalities and cardiovascular disease risk factors.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Cardiovascular Diseases; Female; Humans; Insulin Resistance; Linear Models; Male; Metabolic Syndrome; Middle Aged; Olanzapine; Prospective Studies; Retinol-Binding Proteins, Plasma

Previous research indicates that common single-nucleotide polymorphisms (SNPs) in the serotonin 5-HT2C receptor gene (HTR2C) are associated with metabolic syndrome (MetS) related to antipsychotic treatment. This study analyzes a large sample of patients with schizophrenia treated with atypical antipsychotics to determine whether variation in the HTR2C is associated with MetS.. Six tag SNPs, capturing all common genetic variations in the HTR2C gene in the Han population, were genotyped in 456 Chinese schizophrenic inpatients treated with atypical antipsychotics (clozapine: 171, olanzapine: 91, and risperidone: 194).. Single-marker based analysis shows that of the six HTR2C SNPs, the rs498177 SNP showed a significant association with MetS in female patients, and the C allele was associated with an increased risk of MetS (for genotype TT/TC/CC: MetS vs. non-MetS=50%/27%/23% vs. 69%/28%/3%, and for allele T/C: MetS vs. non-MetS=63%/37% vs. 83%/17%, p=0.0007). Haplotype analysis shows that the A-C type of rs521018-rs498177 in the HTR2C gene significantly decreased the risk of MetS (corrected p=0.0108) in female patients.. The results of this study support the role of HTR2C genetic variants in susceptibility to MetS in patients treated with atypical antipsychotics. However, this association is gender-dependent.

Topics: Adult; Alleles; Antipsychotic Agents; Benzodiazepines; Clozapine; Female; Gene Frequency; Genetic Linkage; Genetic Markers; Genetic Predisposition to Disease; Genetic Variation; Genotype; Haplotypes; Homozygote; Humans; Male; Metabolic Syndrome; Middle Aged; Olanzapine; Polymorphism, Single Nucleotide; Risk Factors; Risperidone; Schizophrenia; Sex Factors

According to current medical opinion chronic mental diseases such as schizophrenia require life-long treatment. The choice of antipsychotics is an important treatment factor, since their side-effects often influence patients' compliance with treatment. Severe side-effects may cause the patients to reject such treatment, the latter being their right. In case a psychiatrist does not agree with the patient's decision to interrupt his antipsychotic treatment regardless its serious side-effects, the former should be persistent in convincing the patient to replace such drug with a more appropriate therapy.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Combined Modality Therapy; Drug Substitution; Female; Humans; Metabolic Syndrome; Olanzapine; Piperazines; Psychotherapy; Schizophrenia; Schizophrenic Psychology; Social Adjustment; Thiazoles; Weight Gain

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Drug Monitoring; Female; Guideline Adherence; Humans; Male; Metabolic Syndrome; Middle Aged; Olanzapine; Practice Patterns, Physicians'; South Africa

Second-generation antipsychotics (SGAs) increase the risk of metabolic syndrome (MetS). Although ethnicity also contributes to MetS risk, the majority of the studies on the relationship of SGAs to this syndrome come from Western countries, whereas few reports have come from Asian countries, especially regarding patients taking a single SGA. We reviewed the electronic medical records of patients with schizophrenia who received aripiprazole, olanzapine or risperidone monotherapies for at least three months. We evaluated the prevalence of MetS in our sample as well as the indirect standardized prevalence ratio (ISPR) using data from the 4th Korean National Health and Nutrition Examination Survey (KNHNES, 2007). The prevalence of MetS in our sample (n=145) was 31.7%, and the ISPR was 2.09. Male patients had a higher prevalence of MetS than female patients (odds ratio [OR]=4.18, 95% CI=1.93-9.03). The ISPR of male patients was 2.67 and statistically significant, whereas the ISPR of female patients was not significant. In our sample, the frequency of abnormal MetS subcomponents occurred in descending order: increased waist circumference, increased triglyceride levels, decreased HDL-cholesterol levels, elevated blood pressure and elevated fasting blood glucose levels. Patients who received aripiprazole were significantly less likely to have MetS. However, a logistic regression showed that age and sex, but not the type of antipsychotic, its dose or the use of antidepressants, were significantly related to the presence of MetS. There were no statistically significant differences among SGAs in terms of MetS subcomponent abnormalities of after adjusting for age and sex. In conclusion, only male Korean patients with schizophrenia who received a monotherapy of aripiprazole, olanzapine or risperidone for more than three months were more likely to have MetS than the general population.

Topics: Adult; Age Factors; Antipsychotic Agents; Aripiprazole; Asian People; Benzodiazepines; Cohort Studies; Databases, Factual; Female; Hospitals, University; Humans; Male; Medical Records; Metabolic Syndrome; Middle Aged; Olanzapine; Piperazines; Quinolones; Republic of Korea; Retrospective Studies; Risperidone; Schizophrenia; Sex Factors; Young Adult

High prevalence of metabolic syndrome (MS) and related metabolic disturbances in patients with schizophrenia and bipolar affective disorder have been in main focus of interest in recent years since the introduction of second-generation antipsychotics. This study aims to examine these questions: 1) Is there a relation between antipsychotic treatment and MS prevalence? 2) Which antipsychotic users have higher MS prevalence? 3) Do patients on antipsychotic polytherapy have higher rates of MS than patients on antipsychotic monotherapy? 4) Which metabolic parameters are considerably disturbed on which antipsychotic users?. 242 Patients with schizophrenia, schizoaffective disorder and bipolar disorder without any other psychiatric comorbidity according to DSM-IV and using the same antipsychotic(s) and/or mood stabilizers at least for the last 6 months included to the final assessment.. The sample was divided into 7 drug groups. The MS prevalence was highest in the combined antipsychotic (AA) group (48.1%) according to ATP III criteria. According to IDF criteria clozapine (C) group had the highest MS prevalence (74%).. When metabolic parameters evaluated overall, metabolic risk with antipsychotics is found to be highest in clozapine group, followed by combined AP group. Olanzapine and risperidone have intermediate risk while zuclopentixole has lowest.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Chi-Square Distribution; Clopenthixol; Clozapine; Cross-Sectional Studies; Female; Humans; Male; Metabolic Syndrome; Middle Aged; Olanzapine; Prevalence; Risk Assessment; Risk Factors; Risperidone; Schizophrenia; Turkey; Young Adult

Serotonin 2C and 2A receptor (5-HT2C and 5-HT2A) antagonisms are hypothesized to play a role in the metabolic adverse effects induced by olanzapine and clozapine. Associations between polymorphisms in 5-HT2C and 5-HT2A receptor coding genes, HTR2C and HTR2A, with antipsychotic-induced weight gain have been reported. The impact of HTR2C and HTR2A polymorphisms on body mass index (BMI), glucose-insulin homeostasis, and blood lipid levels was evaluated in 46 patients with schizophrenia or schizoaffective disorder and treated with olanzapine (n = 28) or clozapine (n = 18) for at least 6 months. Olanzapine-treated patients with HTR2C haplotype C (-759C, -697C, and 23Ser) had higher BMI (P = 0.029) and C peptide levels (P = 0.029) compared with patients with haplotype B (-759T, -697C, and 23Cys). The frequency of patients homozygous for the HTR2C haplotype A (-759C, -697G, and 23Cys) was significantly higher among clozapine-treated patients with obesity (BMI >/= 30 kg/m) compared with nonobese patients (P = 0.015; odds ratio, 28; 95% confidence interval, 2-380). Patients carrying the HTR2A haplotype 2 (-1438A, 102T, and 452His) had significantly higher C peptide levels compared with haplotype 3 (-1438A, 102T, and 452Tyr) carriers in the olanzapine group (P = 0.034) and in the overall study population (P = 0.019). None of the haplotypes were associated with serum levels of insulin, triglycerides, and cholesterol or with homeostasis model assessment index for insulin resistance. In conclusion, both HTR2C and HTR2A gene polymorphisms seem to be associated with the occurrence of metabolic abnormalities in patients treated with olanzapine or clozapine.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Female; Humans; Male; Metabolic Syndrome; Middle Aged; Olanzapine; Polymorphism, Genetic; Receptor, Serotonin, 5-HT2A; Receptor, Serotonin, 5-HT2C; Schizophrenia; Treatment Outcome

Race is strongly associated with risk for metabolic dysfunction, but there is limited prospective data concerning the impact of race on antipsychotic metabolic outcomes among patients with schizophrenia.. This study is a post hoc analysis of data from a 26-week, double-blind, randomized trial of aripiprazole (N = 155) and olanzapine (N = 159) conducted from April 2000 through June 2001 in patients aged >or= 18 years with acute schizophrenia according to DSM-IV criteria. The data were analyzed on the basis of racial breakdown: white and black/Hispanic. Between-drug and within-drug outcomes were analyzed separately for each racial cohort across weight, lipid, and glucose parameters.. For white subjects (N = 167), olanzapine significantly worsened all metabolic parameters except high-density lipoprotein (HDL) cholesterol and fasting glucose, and this was significantly different than aripiprazole for every outcome except fasting glucose. In the black/Hispanic cohort (N = 137), olanzapine treatment resulted in adverse metabolic outcomes, and these changes were significantly different from aripiprazole for adiposity, total cholesterol, and non-HDL cholesterol. Aripiprazole decreased the odds of endpoint metabolic syndrome compared with olanzapine for all subjects (OR = 0.33, 95% CI = 0.19 to 0.55), the white cohort (OR = 0.20, 95% CI = 0.10 to 0.41), and black/Hispanic subjects (OR = 0.53, 95% CI = 0.25 to 1.12), but the black/Hispanic result was not statistically significant (p = .096). Within the aripiprazole group, white subjects had significantly lower risk for metabolic syndrome, but there was no significant difference in metabolic syndrome between white and black/Hispanic subjects exposed to olanzapine.. Race may be an important moderator of metabolic risk during atypical antipsychotic therapy. Olanzapine treatment is associated with greater effects on adiposity and lipids than aripiprazole in both white and black/Hispanic subjects, suggesting that antipsychotic choice and intensive monitoring are important in minimizing metabolic risk, especially in nonwhite patients.

Topics: Acute Disease; Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Black or African American; Blood Glucose; Body Weight; Cholesterol, HDL; Cholesterol, LDL; Double-Blind Method; Female; Hispanic or Latino; Humans; Hypercholesterolemia; Male; Metabolic Syndrome; Middle Aged; Obesity; Olanzapine; Piperazines; Quinolones; Randomized Controlled Trials as Topic; White People; Young Adult

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

The aim of this study was to model in mice the association between metabolic syndrome and the administration of atypical antipsychotic (AAP). Two dosages (4 and 8 mg/kg per day) of olanzapine (OL) were infused in 36 female mice for 30 days by osmotic mini-pumps. This study was also designed to further extend the implications raised in other experiments by our model of AAP-induced metabolic dysregulation. Through the use of the osmotic mini-pumps, this model is aimed to circumvent the shorter (than in humans) half-life of AAPs in rodents and to chronically administer OL by a reliable and less disturbing method. Indirect calorimetry was used to evaluate metabolic rate (MR) and respiratory exchange ratio together with weight and caloric intake. Serum insulin, leptin, and glucose tolerance (oral glucose tolerance test) were assessed. Pancreatic beta cells insulin levels, periuterine and liver fat content were also analyzed. Olanzapine-infused mice exhibited a reduction of overall MR (kilojoule per hour) and resting MR and respiratory exchange ratio, with periuterine fat significantly enlarged. All metabolic alterations were detected at the highest dose, with major effects found on weight gain and hyperphagia. Impaired glucose metabolism, associated with hyperinsulinemia and hyperleptinemia were found. Insulin resistance was evidenced by the raise of HOMA-IR index. Increased insulin and lipid storage were detected at pancreatic and hepatic levels respectively. These findings illustrate the development of a cluster of risk factors (metabolic syndrome) and, for the first time, a decrease of energy expenditure (MR) due to chronic OL infusion.

Topics: Animals; Benzodiazepines; Body Weight; Dyslipidemias; Energy Metabolism; Female; Glucose Intolerance; Infusion Pumps, Implantable; Infusions, Intravenous; Insulin Resistance; Metabolic Syndrome; Mice; Olanzapine; Time Factors

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

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; China; Cross-Sectional Studies; Dose-Response Relationship, Drug; Dyslipidemias; Female; Humans; Male; Metabolic Syndrome; Olanzapine; Pilot Projects; Risk Factors; Risperidone; Schizophrenia; Sex Factors; Young Adult

Antipsychotic (AP) treatment, in particular with some second-generation drugs, is associated with weight gain and other metabolic side effects. However, the relationship between drug-induced weight gain and dyslipidemia is not well understood. We investigated how cardiometabolic risk factors were related to body mass during treatment with different APs under real-life conditions.. This cross-sectional naturalistic study included 242 subjects with severe mental disorders who were on monotherapy with olanzapine (OLZ) or clozapine (CLZ) (n = 80), monotherapy with other APs (n = 80), or unmedicated (n = 82). Groups were adjusted for age and compared for prevalence of the metabolic syndrome and its components. Groups were further adjusted for body mass and compared for mean values of blood pressure, lipids, and fasting glucose.. There was no significant intergroup difference in the prevalence of metabolic syndrome, obesity, hypertension, or hyperglycemia. Despite similar body mass index, OLZ/CLZ-treated subjects had significantly higher prevalence of dyslipidemia (high triglyceride and low HDL cholesterol levels) than unmedicated subjects. They also had higher mean values of triglycerides (P = 0.003) and lower mean values of HDL cholesterol (P < 0.001). Patients treated with other APs had intermediate values.. Intergroup differences in body mass index were minimal in this naturalistic setting, probably because of awareness of this treatment hazard among clinicians. However, independently of body mass, dyslipidemia was significantly associated with AP treatment, in particular with OLZ and CLZ. These findings indicate a primary effect of APs on lipid regulation, important in understanding their mechanism of action, and with clinical implications.

Topics: Adolescent; Adult; Age Factors; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Cholesterol, HDL; Clozapine; Cross-Sectional Studies; Drug Therapy, Combination; Dyslipidemias; Female; Humans; Hypertension; Male; Metabolic Syndrome; Middle Aged; Obesity; Olanzapine; Prevalence; Psychotic Disorders; Schizophrenia; Sex Factors; Triglycerides; Weight Gain

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Humans; Male; Metabolic Syndrome; Olanzapine; Schizophrenia; Weight Gain

This is the first study in bipolar patients, aimed to evaluate possible roles of the drugs, [atypical antipsychotics (AA) and mood stabilizers (MS)], inducing metabolic syndrome (MetS).. 125 bipolar patients, diagnosed according to the DSM IV, were assessed cross-sectionally for MetS according to the National Cholesterol Educational Program criteria (NCEP ATP III). Patients included in the study were required to receive medications (AAs: quetiapine, risperidone and olanzapine, and MSs: Lithium, Sodium Valproate, Carbamazepine, Lamotrigine) for at least 3 months. Patients are divided into three groups as only AA users, AA+MS users and only MS users.. Of the patients, 32% were MetS, a proportion higher than normal population and similar as previous studies in bipolar patients. AA taking patients had significantly higher MetS rates than the others (chi(2)=10.47 df=2 p=0.005). Also, AA taking patients had significantly higher MetS rates than MS taking patients (chi(2)=8.86 df=1 p=0.003). There was no significant difference among quetiapine, olanzapine, risperidone usage for MetS prevalences (chi(2)=0.38 df=2 p=0.82).. AA taking bipolar patients had higher MetS rates. Despite already existing data on MetS and antipsychotics, this cross-sectional study is the first research, discusses AAs and MSs for inducing MetS in bipolar disorder. Prospectively designed researches should be conducted for further clarification of the role of these drugs in MetS.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Body Mass Index; Carbamazepine; Cross-Sectional Studies; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Female; Humans; Lamotrigine; Lithium Carbonate; Male; Metabolic Syndrome; Middle Aged; Olanzapine; Prevalence; Quetiapine Fumarate; Risperidone; Severity of Illness Index; Triazines; Valproic Acid

Although it is generally accepted that atypical antipsychotics differ in their risk for diabetic side effects, the underlying pharmacological mechanisms are unknown. Studies on the mechanisms of antipsychotic-induced hyperglycemia or insulin resistance are often confounded by the concomitant weight gain and dyslipidemia, known diabetic risk factors. To investigate whether antipsychotics can acutely cause metabolic effects before any change in body composition, we studied the effects of four atypical antipsychotics on whole-body insulin resistance. Using the hyperinsulinemic, euglycemic clamp technique in conscious rats, insulin and somatostatin were infused at a constant rate to provide constant hyperinsulinemia and to suppress pancreatic insulin secretion. Glucose was infused at a variable rate, adjusted to maintain euglycemia. At steady state, animals were administered vehicle (V) or antipsychotic and the glucose infusion rate was monitored as an index of insulin sensitivity. Clamp experiments using radiotracers and studies on glucose uptake into isolated skeletal muscle were conducted to differentiate between effects on hepatic glucose production (HGP) and on peripheral glucose uptake. Olanzapine (OLAN) and clozapine (CLOZ) acutely impaired whole-body insulin sensitivity in a dose-dependent manner (P<0.001 vs V), whereas ziprasidone and risperidone had no effect. CLOZ also induced profound insulin resistance after dosing 10 mg/kg/day for 5 days (P<0.05 vs V). Tracer studies indicated that acute changes mainly reflect increased HGP, consistent with the lack of effect on glucose uptake. OLAN and CLOZ can thus rapidly induce marked insulin resistance, which could contribute to the hyperglycemia and ketoacidosis reported for patients receiving those therapies.

Topics: Acute Disease; Animals; Antipsychotic Agents; Benzodiazepines; Clozapine; Disease Models, Animal; Dose-Response Relationship, Drug; Energy Metabolism; Glucose; Hyperglycemia; Insulin; Insulin Resistance; Liver; Male; Metabolic Syndrome; Muscle, Skeletal; Olanzapine; Rats; Rats, Wistar; Somatostatin

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Blood Pressure; Cross-Sectional Studies; Dibenzothiazepines; Double-Blind Method; Female; Follow-Up Studies; Humans; Metabolic Syndrome; Olanzapine; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenia, Paranoid; Triglycerides; Waist-Hip Ratio

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

Clozapine and olanzapine treatment has been associated with insulin resistance in non-obese schizophrenia patients. Much less is known regarding other agents such as quetiapine. The objective of this study was to compare matched olanzapine- and quetiapine-treated schizophrenia patients and normal controls on measures of glucose metabolism.. A cross-sectional comparison of quetiapine-treated and olanzapine-treated non-obese (body mass index < 30.0 kg/m2) schizophrenia subjects (DSM-IV) with matched normal controls using a frequently sampled intravenous glucose tolerance test and nutritional assessment was conducted from April 2002 to October 2004. Data from 24 subjects were included in the analysis (7 quetiapine, 8 olanzapine, 9 normal controls).. There was a significant difference among groups for fasting baseline plasma glucose concentrations (p = .02), with olanzapine greater than normal controls (p = .01). The insulin sensitivity index (SI) differed significantly among groups (p = .039); olanzapine subjects exhibited significant insulin resistance compared to normal controls (p = .01), but there was no significant difference for quetiapine versus olanzapine (p = .1) or quetiapine versus normal controls (p = .40). SI inversely correlated with quetiapine dose (p = .0001) and waist circumference (p = .03) in quetiapine-treated subjects. Insulin resistance calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) also differed significantly among groups (p = .03). The olanzapine group had a higher HOMA-IR level than normal controls (p = .01). There was a significant difference in glucose effectiveness (SG) among the groups (p = .049). SG was lower in the olanzapine group than in the quetiapine group (p = .03) and in the olanzapine group compared to normal controls (p = .049).. Our findings are consistent with our previous report that nonobese olanzapine-treated subjects showed insulin resistance, measured by both HOMA-IR and SI, and reduction in SG. Studies that include larger samples, unmedicated patients, and varying durations of antipsychotic exposure are necessary to confirm these results.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Mass Index; Body Weight; Cross-Sectional Studies; Dibenzothiazepines; Female; Follow-Up Studies; Glucose; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Male; Metabolic Syndrome; Middle Aged; Nutrition Assessment; Olanzapine; Quetiapine Fumarate; Risk Factors; Schizophrenia

To assess the perceptions of clinicians in the psychiatric community about pharmacotherapy and its impact on weight gain and adverse metabolic effects in patients with bipolar disorder.. In November 2005, self-administered questionnaires were sent to 7000 psychiatrists who treat bipolar disorder in their clinical practice. An additional mailing of these questionnaires was sent in January 2006 to a different group of 7000 psychiatrists who treat bipolar disorder in their clinical practice. The first 298 completed surveys were analyzed.. Almost half of the respondents (48%) were psychiatrists in individual private practice and 32% were in community mental health centers. About two-thirds of respondents reported that 30-60% of their bipolar patients were overweight. Thirty-eight percent of respondents reported metabolic syndrome present in 20-40% of their patients. Almost all respondents (96%) reported a 20 lb increase in patients' weight as a troublesome potential adverse event associated with the use of some agents. After initiating a new medication, more than 80% of respondents monitored their patients' weight, fasting plasma glucose level, and fasting lipid profile at regular intervals. However, 80% did not monitor waist circumference. Overall, respondents viewed several agents (aripiprazole, ziprasidone, carbamazepine, and lamotrigine) as not (or minimally) problematic in terms of weight gain and adverse metabolic concerns. Clozapine and olanzapine were viewed as highly problematic due to their propensity to induce weight gain and negatively influence lipid and glucose metabolism. Other agents considered to be minimally to moderately problematic in terms of weight gain and metabolic issues were quetiapine, risperidone, lithium, and valproate. Respondents reported that the profile of a bipolar agent in terms of weight gain and adverse metabolic effects was an important consideration in the management of bipolar disorder.. Although the study is limited by a low response rate and self-selection of respondents, clinicians who did respond were concerned about the risks of weight gain and metabolic disturbances in their patients treated with bipolar agents. For most parameters, such concerns were being integrated into clinical care. However, it appears that there is a need to increase clinicians' appreciation of the importance of abdominal obesity and the need to monitor waist circumference. A growing recognition of the differences in weight-gain potential and adverse metabolic effects among agents appears to have had a definite impact on prescribing patterns in the management of bipolar disorder.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Blood Glucose; Clozapine; Female; Humans; Lipids; Male; Metabolic Syndrome; Olanzapine; Overweight; Perception; Practice Patterns, Physicians'; Weight Gain

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

Topics: Antipsychotic Agents; Benzodiazepines; Bias; Biomarkers; Coronary Artery Disease; Cross-Sectional Studies; Fasting; Humans; Metabolic Syndrome; Olanzapine; Research Design; Risk Factors; Risperidone

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Drug Prescriptions; Humans; Hypersensitivity; Male; Medication Errors; Metabolic Syndrome; Obesity; Olanzapine; 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

Second generation antipsychotics (SGA) are obesitogenic and diabetogenic. Role of ghrelin (RIA), resistin and TNF-alpha (ELISA) in weight gain and insulin resistance (fasting plasma insulin, HOMA, ELISA) was studied in Hungarian psychiatryic patients (n=60) treated with SGA (clozapine, olanzapine, risperidone, quetiapine, 15 each). After 1 year, 80% of patients became overweight/obese (BMI > 27/30) and 35% (n= 21/60) presented impaired glucose tolerance (13/60) or diabetes (8/60). Ghrelin (1.3 +/- 0.6 ng/ml), resistin (9.8 +/- 3.7 ng/ml), TNF-alpha (5.8 +/- 1.7 pg/ml), insulin (10.4 +/- 7.6 U/ml, HOMA A: 2.5 +/- 1.8, HOMA B: 133 +/- 62.5) were significantly higher in patients than in healthy matched controls. Resistin and TNF-alpha positively correlated with each other, insulin, HOMA, and negatively with ghrelin. Ghrelin contributes to weight gain, resistin and TNF-alpha to insulin resistance. A negative feedback regulation may exist between adipocytokines and ghrelin production. SGA drugs enhance ghrelin production despite the suppressive effect of adipocytokines. All four SGA drugs are equally obesitogenic and diabetogenic.

Topics: Antipsychotic Agents; Benzodiazepines; Carbohydrate Metabolism; Case-Control Studies; Clozapine; Dibenzothiazepines; Female; Ghrelin; Humans; Insulin Resistance; Male; Metabolic Syndrome; Middle Aged; Obesity; Olanzapine; Overweight; Peptide Hormones; Quetiapine Fumarate; Resistin; Risperidone; Tumor Necrosis Factor-alpha; 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: Antipsychotic Agents; Benzodiazepines; Body Weight; Female; Humans; Insulin; Leptin; Male; Metabolic Syndrome; Obesity; Olanzapine; Pirenzepine; Psychotic Disorders