quetiapine-fumarate and Metabolic-Syndrome

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

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

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

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

Individuals with bipolar disorder have high rates of other medical comorbidity, which is associated with higher mortality rates and worse course of illness. The present study examined common predictors of medical comorbidity.. The Clinical and Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder study (Bipolar CHOICE) enrolled 482 participants with bipolar I or bipolar II disorder in a six-month, randomized comparative effectiveness trial. Baseline assessments included current and lifetime DSM-IV-TR diagnoses, demographic information, psychiatric and medical history, severity of psychiatric symptoms, level of functioning, and a fasting blood draw. Medical comorbidities were categorized into two groups: cardiometabolic (e.g., diabetes, hyperlipidemia, and metabolic syndrome) and non-cardiovascular (e.g., seizures, asthma, and cancer). Additionally, we looked at comorbid substance use (e.g., smoking and drug dependence).. We found that 96.3% of participants had at least one other medical comorbidity. Older age predicted a greater likelihood of having a cardiometabolic condition. Early age of onset of bipolar symptoms was associated with a lower chance of having a cardiometabolic condition, but a greater chance of having other types of medical comorbidity. Additional predictors of other medical comorbidities in bipolar disorder included more time spent depressed, less time spent manic/hypomanic, and longer duration of illness. Medications associated with weight gain were associated with low high-density lipoprotein and abnormal triglycerides.. There appears to be a substantial medical burden associated with bipolar disorder, highlighting the need for collaborative care among psychiatric and general medical providers to address both psychiatric and other medical needs concomitantly in this group of patients.

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Asthma; Bipolar Disorder; Cardiovascular Diseases; Comorbidity; Comparative Effectiveness Research; Diabetes Mellitus; Diagnostic and Statistical Manual of Mental Disorders; Female; Humans; Hyperlipidemias; Lithium Compounds; Male; Metabolic Syndrome; Middle Aged; Neoplasms; Quetiapine Fumarate; Seizures; Smoking; Substance-Related Disorders

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

To determine the risk of developing obesity and related metabolic complications in children following long-term treatment with risperidone or quetiapine.. This was a 1-year naturalistic longitudinal study conducted between February 2009 and March 2012. A total of 130 children aged 2 to 18 years without prior exposure to second-generation antipsychotics (SGAs) were enrolled at initiation of treatment with either risperidone or quetiapine. Metabolic parameters were measured at baseline and months 6 and 12. Data of 37 participants (20 treated with risperidone and 17 treated with quetiapine) who completed 12-month monitoring were used in the analysis.. After 1 year of SGA treatment, mean weight increased significantly by 10.8 kg (95% CI 7.9 kg to 13.7 kg) for risperidone and 9.7 kg (95% CI 6.5 kg to 12.8 kg) for quetiapine. Body mass index z score also increased significantly in both groups (P < 0.001). There was a high incidence of children becoming overweight or obese (6/15 [40.0%] for risperidone-treated and 7/14 [50.0%] for quetiapine-treated). The mean levels of fasting glucose (for risperidone-treated) and ratio of total cholesterol to high-density lipoprotein cholesterol (for quetiapine-treated) increased significantly by 0.23 mmol/L (95% CI 0.03 mmol/L to 0.42 mmol/L) and 0.48 mmol/L (95% CI 0.15 mmol/L to 0.80 mmol/L), respectively.. Children treated with risperidone or quetiapine are at a significant risk for developing obesity, elevated waist circumference, and dyslipidemia during 12 months of treatment. These data emphasize the importance of regular monitoring for early identification and treatment of metabolic side effects.

Topics: Adolescent; Antipsychotic Agents; Anxiety Disorders; Attention Deficit and Disruptive Behavior Disorders; Blood Pressure; Body Mass Index; British Columbia; Child; Child Development Disorders, Pervasive; Child, Preschool; Cholesterol; Cholesterol, HDL; Cohort Studies; Dyslipidemias; Female; Humans; Incidence; Longitudinal Studies; Male; Mental Disorders; Metabolic Syndrome; Mood Disorders; Obesity; Overweight; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate; Risk Factors; Risperidone; Waist Circumference

Topics: Antipsychotic Agents; Humans; Male; Metabolic Syndrome; Quetiapine Fumarate; Schizophrenia; Young Adult

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

Rapid weight gain among patients with mental disorders can further compound psychological distress and negatively influence compliance. Weight gain associated with treatment with atypical antipsychotic medication has been widely recognized as a risk factor for the development of diabetes type II and cardiovascular diseases. This paper describes a 33-year old female patient treated for schizoaffective disorder. Within two months after introducing quetiapine the patient experienced considerable weight gain amounting to 19 kg. The replacement of antipsychotic during inpatient psychiatric care resulted in weight loss.

Topics: Adult; Antipsychotic Agents; Body Mass Index; Dibenzothiazepines; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Metabolic Syndrome; Patient Admission; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Thiazoles; Weight Gain

In clinical trials multiple outcomes are often used to assess treatment interventions. This paper presents an evaluation of likelihood-based methods for jointly testing treatment effects in clinical trials with multiple continuous outcomes. Specifically, we compare the power of joint tests of treatment effects obtained from joint models for the multiple outcomes with univariate tests based on modeling the outcomes separately. We also consider the power and bias of tests when data are missing, a common feature of many trials, especially in psychiatry. Our results suggest that joint tests capitalize on the correlation of multiple outcomes and are more powerful than standard univariate methods, especially when outcomes are missing completely at random. When outcomes are missing at random, test procedures based on correctly specified joint models are unbiased, while standard univariate procedures are not. Results of a simulation study are reported, and the methods are illustrated in an example from the Clinical Antipsychotic Trials of Intervention Effectiveness for schizophrenia.

Topics: Antipsychotic Agents; Biostatistics; Clinical Trials as Topic; Dibenzothiazepines; Humans; Likelihood Functions; Linear Models; Metabolic Syndrome; Models, Statistical; Multivariate Analysis; Outcome Assessment, Health Care; Perphenazine; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Schizophrenia; Treatment Outcome

Topics: Antipsychotic Agents; Anxiety Disorders; Death, Sudden, Cardiac; Depressive Disorder, Major; Dibenzothiazepines; Dyskinesia, Drug-Induced; Humans; Metabolic Syndrome; Quetiapine Fumarate; Risk Factors; United States; United States Food and Drug Administration; Weight Gain

Topics: Adult; Anti-Bacterial Agents; Antipsychotic Agents; Clarithromycin; Dibenzothiazepines; Drug Interactions; Drug Overdose; Humans; Male; Metabolic Syndrome; Psychotic Disorders; Quetiapine Fumarate

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

To determine whether the coprescribing of two or more antipsychotics, a relatively frequent practice with little data to support its safety and efficacy, is associated with an increased prevalence of metabolic syndrome.. 364 newly admitted adults treated with second-generation antipsychotics underwent assessments evaluating antipsychotic polytherapy, and of the presence of metabolic syndrome and triglycerides/high-density lipoprotein cholesterol ratio>3.5 (TG/HDL), a sensitive marker of insulin resistance. The correlates of antipsychotic polytherapy and associations with metabolic syndrome and TG/HDL were determined by univariate comparisons and multiple logistic regression analyses.. Antipsychotic polytherapy was present in 70 patients (19.2%) and was significantly more likely in patients with schizophrenia and those treated with clozapine, quetiapine or ziprasidone (p<0.0001). Compared with antipsychotic monotherapy, polytherapy was associated with elevated rates of metabolic syndrome (50.0% vs. 34.3%, p=0.015) and TG/HDL (50.7% vs. 35.0%, p=0.016). However, in logistic regression analyses, metabolic syndrome was significantly associated with higher body mass index (BMI), older age, a diagnosis of bipolar disorder or schizophrenia, and cotreatment with a first-generation antipsychotic (r(2): 0.25, p<0.0001). The TG/HDL marker of insulin resistance was associated with higher BMI, male sex, Caucasian race and absence of aripiprazole treatment (r(2): 0.14, p<0.0001). Antipsychotic polypharmacy dropped out of both multivariate models.. Compared with patients receiving antipsychotic monotherapy, patients on antipsychotic polytherapy have higher rates of metabolic syndrome and lipid markers of insulin resistance. However, antipsychotic polytherapy is not independently associated with the prevalence of these abnormalities, which are related to known demographic, clinical and anthropometric risk factors.

Topics: Adult; Age Factors; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Body Mass Index; Cholesterol, HDL; Clozapine; Cross-Sectional Studies; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Insulin Resistance; Male; Metabolic Syndrome; Middle Aged; Piperazines; Quetiapine Fumarate; Quinolones; Risk Factors; Schizophrenia; Thiazoles; Triglycerides

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

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

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