quetiapine-fumarate and Diabetes-Mellitus--Type-2

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

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

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

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

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

Chlorprothixene is commonly used off-label in low doses for sedative-hypnotic purposes although it might carry a risk of cardiometabolic adverse events due to its pharmacodynamic profile. We investigated the risk of diabetes and major adverse cardiovascular events (MACE) with use of low-dose chlorprothixene, compared with use of low-dose quetiapine in a nationwide cohort study, including all new users of low-dose chlorprothixene (n = 81 328) and low-dose quetiapine (n = 91 163) in Denmark 2000-2017. Main outcomes were diabetes and MACE (myocardial infarction, stroke and death from cardiovascular causes). The association between cumulative dose of chlorprothixene and the outcomes was tested in a case-control analysis. Low-dose chlorprothixene use was associated with increased risk of diabetes (intention-to-treat [ITT]-hazard ratio [HR]: 1.16; 95% CI: 1.08-1.25), compared with low-dose quetiapine use. This association strengthened when follow-up was restricted to time on treatment (as-treated [AT]-HR: 1.34; 95% CI: 1.14-1.56). Low-dose chlorprothixene use was also associated with increased risk of MACE (ITT-HR: 1.12; 95% CI: 1.04-1.21) and stroke (ITT-HR: 1.21; 95% CI: 1.06-1.37) but not with myocardial infarction (ITT-HR: 1.11; 95% CI: 0.95-1.30) nor death from cardiovascular causes (ITT-HR: 1.07; 95% CI: 0.96-1.20). Cumulative dose of chlorprothixene ≥6000 mg was associated with increased risk of diabetes (OR: 1.15-1.63; test for trend: p < 0.001), whereas cumulative dose of chlorprothixene ≥1500 mg was associated with increased risk of MACE (OR: 1.10-1.85; test for trend: p < 0.001). In conclusion, low-dose chlorprothixene use is associated with increased risk of cardiometabolic adverse events compared with low-dose quetiapine use.

Topics: Cardiovascular Diseases; Chlorprothixene; Cohort Studies; Diabetes Mellitus, Type 2; Humans; Myocardial Infarction; Quetiapine Fumarate; Risk Factors

Quetiapine has been associated with increased risk of type 2 diabetes when used in medium or high doses for the treatment of severe mental disorders. It is not known whether low doses, commonly used off-label for sedative-hypnotic purposes, are also associated with increased risk of type 2 diabetes.. To investigate whether there is an association between prescription of low-dose quetiapine and the risk of type 2 diabetes.. This cohort study examined nationwide Danish health registers for data regarding new users of quetiapine (n = 185 938) or selective serotonin reuptake inhibitors (SSRIs) (n = 1 031 920) who were aged 18 years or older between January 1, 1998, and December 31, 2018. Individuals with schizophrenia or bipolar disorder were excluded. Quetiapine-initiators were matched 1:1 with initiators of SSRIs, using a high-dimensional propensity score (hdPS). Maximum follow-up was 5 years. Association with cumulative dose was investigated, using a case-control approach nested among quetiapine users. Data analysis was performed from May to September 2020.. Dispensing of quetiapine or SSRIs. Quetiapine prescriptions were limited to tablet strengths of 25 mg and 50 mg to focus on low-dose use.. Incident type 2 diabetes was defined as first filling of an antidiabetic medication, first register diagnosis of type 2 diabetes or first hemoglobin A1C measurement greater than or equal to 6.4% (≥48 mmol/mol). Incidence rates (IRs), incidence rate ratios (IRRs), and number-needed-to-harm (NNH) were calculated for full and matched cohorts using as-treated and intention-to-treat approaches. Odds ratios (ORs) were calculated for the association with cumulative quetiapine dose.. Altogether, 896 285 patients were included in the full cohort; 538 164 (60%) were female and the median (interquartile range) age was 47 (33-67) years. There were 57 701 low-dose quetiapine initiators and 838 584 SSRI initiators. The matched cohort consisted of 54 616 pairs. In as-treated analyses, the incidence of type 2 diabetes during treatment with low-dose quetiapine (425 cases) was 9.59 cases/1000 person-years (PY) (95% CI, 8.72-10.5/1000 PY), which was slightly higher than for SSRI users (8462 cases; IR, 8.13/1000 PY; 95% CI, 7.96-8.30/1000 PY), resulting in a significant IRR of 1.18 (95% CI, 1.07-1.30) and NNH of 684 (95% CI, 418-1873). However, the between-group difference was nonsignificant in the hdPS-matched cohort (IR, 9.49 vs IR, 9.58; IRR, 0.99; 95% CI, 0.87-1.13). The case-control analysis found no dose-response association of low-dose quetiapine with diabetes (OR for doubling of the cumulative dose: 1.02; 95% CI, 0.95-1.09; P = .54), but in sensitivity analyses higher daily doses were associated with diabetes (all tablet strengths: OR, 1.08; 95% CI, 1.03-1.13).. In this cohort study, use of low-dose quetiapine was not associated with excess risk of type 2 diabetes in comparison with SSRIs.

Topics: Adult; Aged; Antipsychotic Agents; Case-Control Studies; Denmark; Diabetes Mellitus, Type 2; Female; Humans; Incidence; Intention to Treat Analysis; Male; Middle Aged; Quetiapine Fumarate; Risk Factors; Selective Serotonin Reuptake Inhibitors

Minimizing the duration of untreated psychosis and providing comprehensive early intervention including the use of antipsychotics reflects best practice in the treatment of first-episode psychosis (FEP).

Topics: Adolescent; Adult; Antipsychotic Agents; Aripiprazole; Cardiovascular Diseases; Child; Clinical Decision-Making; Diabetes Mellitus, Type 2; Humans; Psychotic Disorders; Quetiapine Fumarate

Use of second-generation antipsychotics (SGAs) for treatment of depression has increased, and patients with depression and comorbid diabetes or cardiovascular disease are more likely to use SGAs than those without these conditions. We compared SGA and non-SGA depression pharmacotherapies on the risk of diabetes hospitalization or treatment intensification in adults with depression and preexisting diabetes.. This was a retrospective cohort study of US commercially insured adults (2009-2015 Truven MarketScan Commercial Claims and Encounters Database) aged 18-64 years old with type 2 diabetes mellitus and unipolar depression previously treated with a selective serotonin reuptake inhibitor or serotonin-norepinephrine reuptake inhibitor. New users of SGAs versus non-SGAs, as well as specific treatments (aripiprazole, quetiapine, bupropion, mirtazapine, and tricyclic antidepressants [TCAs]) were matched on class/medication-specific high-dimensional propensity score. Cox proportional hazard models were used to compare the risk of diabetes-related hospitalization or treatment intensification.. We identified 6,625 SGA (aripiprazole = 3,461; quetiapine = 1,977; other = 1,187) and 23,921 non-SGA patients for inclusion (bupropion = 15,511; mirtazapine = 1,837; TCAs = 5,989; other = 584) with a mean age of 51 years. In the matched cohort, the rate of diabetes-related hospitalization or drug intensification was 47.9 per 100 person-years in the SGA group and 43.5 per 100 person-years in the non-SGA group (adjusted hazard ratio [aHR] = 1.03; 95% CI, 0.96-1.11). When comparing treatment subgroups, the risk of events was lower for bupropion versus TCAs (aHR = 0.85; 95% CI, 0.76-0.98), quetiapine versus mirtazapine (aHR = 0.82; 95% CI, 0.67-0.99), and quetiapine versus TCAs (aHR = 0.84; 95% CI, 0.72-0.98). For other comparisons, differences were small and not statistically significant.. While drug-specific effects on risk of diabetes hospitalization or treatment intensification most likely guide clinical decision making, we observed only modest differences in risk. The overall impact of SGAs on diabetes control depends not only on direct effects on glucose metabolism but also on effectiveness of depression symptom relief. Future studies evaluating other diabetes outcomes (glycosylated hemoglobin, diabetes complications) are needed.

Topics: Adolescent; Adult; Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Antipsychotic Agents; Bupropion; Comorbidity; Depressive Disorder; Diabetes Mellitus, Type 2; Female; Hospitalization; Humans; Male; Mianserin; Middle Aged; Mirtazapine; Proportional Hazards Models; Quetiapine Fumarate; Retrospective Studies; Young Adult

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

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

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

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

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

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

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

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

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

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

Topics: Adult; Antipsychotic Agents; Blood Glucose; Body Mass Index; Clozapine; Diabetes Mellitus, Type 2; Dibenzothiazepines; Diet, Diabetic; Drug Therapy, Combination; Female; Fluphenazine; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Male; Mass Screening; Quetiapine Fumarate; Risk Factors; Schizophrenia

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

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

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

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

New onset diabetes mellitus (DM) and diabetic ketoacidosis (DKA) among patients using atypical antipsychotics is of clinical importance [1,2,5,7-10]. Recently, atypical antipsychotics have been more widely used in the treatment of behavioral and psychological symptoms with dementia (BPSD) than conventional neuroleptics because of a reduced tendency for movement disorders and psychomotor retardation. We report a case of reversible DKA and new-onset DM that developed in a demented patient who was treated with quetiapine for 14 days.

Topics: Aged; Alcoholism; Antipsychotic Agents; Dementia; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Dibenzothiazepines; Humans; Male; Quetiapine Fumarate

To draw attention to severe presentations of atypical neuroleptic related diabetes and to document that a marked degree of remission can take place after drug withdrawal.. We describe two patients who presented with diabetic ketoacidosis after treatment with quetiapine and risperidone, respectively.. Both patients were negative for islet cell antibodies. They both required treatment with insulin, one in very high dosage, but their insulin requirements fell progressively after the atypical antipsychotic was withdrawn. After several months, neither patient required antidiabetic treatment.. Atypical antipsychotic-induced diabetes does not always take a "type 2" presentation in which weight gain and insulin resistance are implicated. Sometimes the presentation is with diabetic ketoacidosis, requiring insulin treatment, which can nevertheless be reversible.

Topics: Adult; Antipsychotic Agents; Diabetes Mellitus, Type 2; Dibenzothiazepines; Female; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Quetiapine Fumarate; Risperidone; Schizophrenia; Severity of Illness Index

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

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

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

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

Topics: Adolescent; Antipsychotic Agents; Bipolar Disorder; Diabetes Mellitus, Type 2; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Hyperglycemia; Hypertriglyceridemia; Quetiapine Fumarate; Risk Factors

Topics: Adult; Antipsychotic Agents; Diabetes Mellitus, Type 2; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Male; Psychotic Disorders; Quetiapine Fumarate