clozapine and Diabetes-Mellitus

The prevalence of Diabetes Mellitus (DM) is becoming a serious public health problem. The use of atypical antipsychotics has been associated with disruption of the glucose metabolism and therefore with causing DM. The underlying mechanisms are unknown, but knowledge of the differences between the pharmacological features of various antipsychotics combined with their diabetogenic profile might help us to understand those mechanisms. This article describes how the binding of various essential receptors or transporters in essential body tissues, adipose tissue, pancreatic tissue and liver and skeletal muscle tissue can cause disruption of the glucose metabolism. With such knowledge in mind one can try to explain the differences between the diabetogenic propensities of various antipsychotics. It is well known that clozapine and olanzapine cause weight gain and DM, whereas aripiprazole and ziprasidone have much less disruptive clinical profiles. The most significant risk factor for adiposity seems to be strong blocking of histaminergic receptors. An agonistic activity on serotonergic-1a receptors, with a very low affinity for muscarinergic-3 receptors, might protect against the development of DM. More data will become available which may help to solve the puzzle.

Topics: Adiponectin; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Blood Glucose; Clozapine; Diabetes Mellitus; Humans; Leptin; Obesity; Olanzapine; Piperazines; Quinolones; Receptor, Muscarinic M3; Receptor, Serotonin, 5-HT1A; Receptors, Dopamine D2; Receptors, Histamine; Serotonin 5-HT1 Receptor Agonists; Thiazoles; Weight Gain

Clozapine is an important antipsychotic agent that has a unique profile of clinical benefits, but that has also been associated with several serious and potentially life-threatening safety concerns. In order to minimise the impact of haematological adverse events, health professionals treating patients with clozapine are currently required to register their patients on a centrally administered data network and to conform to strict protocols. The consensus statement documented in this article extends existing protocols by recommending monitoring of patients treated with clozapine for additional adverse effects during treatment. This consensus statement reflects the current practice at five major public psychiatric hospitals in Victoria, Australia, for the monitoring and management of clozapine-related adverse events, and has been implemented at these sites because of emerging safety concerns associating clozapine with cardiovascular and metabolic adverse effects.

Topics: Agranulocytosis; Antipsychotic Agents; Australia; Clozapine; Consensus; Diabetes Mellitus; Humans; Hyperlipidemias; Neutropenia; Population Surveillance; Psychotic Disorders; Weight Gain

Compared with the first-generation, or "typical" antipsychotic drugs, second-generation or atypical antipsychotics cause fewer extrapyramidal (motor) problems, but they pose new challenges, as they often contribute to metabolic disturbances such as weight gain, hyperlipidemia, insulin resistance, and type 2 diabetes mellitus. Patients taking atypical antipsychotics should be monitored for glycemic and cardiovascular risk factors and should receive treatment for such problems as they arise.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Diabetes Mellitus; Humans; Olanzapine; Psychotic Disorders; Risk Factors; Risperidone; Weight Gain

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Diabetes Mellitus; Dibenzothiazepines; Dyslipidemias; Glucose Metabolism Disorders; Humans; Insulin Resistance; Mental Disorders; Obesity; Olanzapine; Phenothiazines; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Thiazoles

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

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

Clozapine is a distinctive antipsychotic agent, having a unique clinical profile and an idiosyncratic safety profile. More so than with other agents, the weighting of its adverse event profile is critical, in order to counterbalance its clear clinical advantages. The safety issues with clozapine are in a number of areas, some of which are considered medical emergencies and potentially life-threatening. These include haematological (neutropenia and agranulocytosis), CNS (seizures), cardiovascular (myocarditis and cardiomyopathy), metabolic (diabetes), gastrointestinal and neuromuscular. Understanding the safety profile of clozapine allows an informed use of the agent that can maximise its clear clinical benefit and minimise the known risks.

Topics: Antipsychotic Agents; Cardiomyopathies; Clozapine; Diabetes Mellitus; Humans; Muscle, Skeletal; Myocarditis; Neutropenia; Psychotic Disorders; Risk Factors; Seizures; Weight Gain

During the last few years, several case reports and studies have been published on the potential diabetes mellitus (DM)-inducing effect of some atypical antipsychotics, especially clozapine and olanzapine. The purpose of our study was to evaluate diabetogenic effects of atypical antipsychotics in the literature. In order to give a full-scale overview, both peer-reviewed publications and oral and poster presentations on this subject were screened. We found 27 case reports of new-onset DM for clozapine, 39 for olanzapine, 4 for risperidone, and 3 for quetiapine. Related to the year of introduction of these drugs on the market and the number of treatment days of each drug during the last 6 years in 13 western countries, Brazil, and Japan, the cases show an over-representation of cases related to olanzapine and clozapine. In the majority of cases, risk factors (DM family history, obesity, Negroid ethnicity) were present. Eighty-four percent of the cases arose in patients < 50 years, in contrast to the general population (most cases, > 50 years). Comparative epidemiological studies point in the same direction, with two studies showing no differences between the atypical drugs. Antipsychotic agents are used often for treatment of schizophrenia, a condition that appears to be associated with DM also in untreated subjects. Some antipsychotics appear to induce new-onset diabetes mellitus. In view of the health risks of DM and the predisposition in patients with schizophrenia, it is advised to be cautious with prescription of antipsychotics that are associated with new-onset DM. Especially in predisposed patients (family history of DM, obese, Negroid ethnicity), reticence in this respect is required. Moreover, careful monitoring of weight, BMI, and glucose levels is advised both before these antipsychotics are prescribed and during treatment.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Diabetes Mellitus; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Olanzapine; Quetiapine Fumarate; Risk; Risperidone; Schizophrenia

The use of atypical antipsychotic agents is associated with the induction of both an indolent progression to insulin-resistant diabetes and an idiosyncratic beta-cell toxicity presenting as diabetic ketoacidosis, both of which are usually reversible or improved subsequent to cessation of treatment. The underlying mechanisms are unclear at present. Nonetheless, in light of the now numerous reports on the adverse metabolic effects of these drugs, the Consensus Development Conference which met in November 2003 recommends that metabolic risks be considered when starting atypical antipsychotic drugs. Their operative checklist includes baseline screening of candidates for antipsychotic treatment, which includes personal/family history of diabetes, weight, waist circumference, blood pressure, fasting plasma glucose and fasting lipid profile, and then follow-up of these parameters. Furthermore, the health professionals, patients, family and caregivers should be aware of the signs and symptoms of diabetes, especially when acute decompensation occurs which is commensurate with diabetic ketoacidosis. We wish, through this short report, to raise the awareness of physicians treating psychiatric patients to the possibility of new-onset diabetes during therapy with atypical antipsychotic drugs and to emphasize the necessity for increased vigilance and close metabolic follow-up of these patients. Moreover, the choice of the best antipsychotic treatment for each patient should take into consideration the diabetogenic effect of the different treatment options as well the other side effects.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Diabetes Mellitus; Diabetic Ketoacidosis; Female; Glucose; Humans; Male; Olanzapine; Risperidone; Schizophrenia

An increased risk for occurrence of diabetic metabolic states has been reported for treatment with atypical antipsychotics. Initial studies suggest that atypical antipsychotics as a heterogeneous group of substances are not equally concerned. An increased risk for development of diabetes mellitus can be assumed for clozapine and olanzapine, while other atypical and conventional antipsychotics seem to carry only a slightly elevated risk. It remains as yet unresolved whether there is a causal connection or whether other not yet identified factors are involved. However, atypical antipsychotics intervene in various ways in glucose and fatty acid metabolism due to their broad receptor profile. We suggest that some atypical antipsychotics disturb regulatory loops of fat metabolism in fatty tissue and muscle,which may result in insulin resistance and finally diabetes. Changes in leptin release and development of leptin resistance possibly play an important role. These new results should be considered when planning therapy, although a final risk analysis is not yet possible.

Topics: Antidepressive Agents, Second-Generation; Antipsychotic Agents; Benzodiazepines; Clozapine; Diabetes Mellitus; Humans; Olanzapine; Patient Care Management; Practice Guidelines as Topic; Risk Assessment; Risk Factors

Topics: Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Diabetes Mellitus; Dibenzothiazepines; Dyskinesias; Haloperidol; Humans; Hyperglycemia; Hyperprolactinemia; Olanzapine; Pirenzepine; Quetiapine Fumarate; Risperidone; Thioridazine; Weight Gain

Diabetes or hyperglycemia associated with the use of atypical anti-psychotic agents is a subject of growing concern among health care providers and the patients who use the drugs. Although much attention has been relegated to this topic in the mental health literature, there has been little attention devoted to it in the diabetes literature. The purpose of this report is to review the problem of diabetes mellitus associated with atypical anti-psychotic use from an endocrinology perspective. This paper will specifically present (a) a review of the increased prevalence of diabetes in the setting of schizophrenia, (b) a compilation and critical assessment of the existing publications that have documented the association of hyperglycemia and atypical anti-psychotic use, (c) a discussion of the potential mechanisms through which antipsychotics may lead to disturbances in glucose homeostasis, and (d) recommendations for the effective monitoring and treatment of affected patients.

Topics: Adult; Aged; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Benzodiazepines; Clozapine; Diabetes Mellitus; Humans; Hyperglycemia; Middle Aged; Odds Ratio; Olanzapine; 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

The pharmacotherapy of schizophrenia remains an ongoing challenge for researchers and clinicians alike. Current medications remain suboptimal to effectively treat this illness despite the recent surge of what are considered to be better antipsychotics: the atypicals. The atypicals cause fewer extrapyramidal symptoms and tardive dyskinesia, but there is growing concern regarding the significant long-term metabolic and cardiac adverse effects of these novel antipsychotics. There are differences among the atypicals in their propensity to produce these adverse effects, and clinicians should weigh the risk-benefit ratio for each drug with each individual patient. Diabetes, heart disease, obesity, and unhealthy lifestyle choices are on the rise in the general population, and individuals with chronic schizophrenia are even more at risk. The dilemma clinicians face in trying to avoid the neurological morbidity of the typicals (extrapyramidal side effects and tardive dyskinesia) is the risk of consequently exposing patients to both the morbidity and potential mortality of the atypicals (cardiovascular, endocrine, and metabolic adverse effects). The importance of baseline investigations and monitoring at regular intervals as well as identification of patients at risk for obesity, diabetes, and cardiovascular morbidity has become crucial. Informed decision making is essential for successful antipsychotic pharmacotherapy. For a condition, which often necessitates long-term pharmacotherapy, the importance of prevention and (or) minimization of morbidity and mortality related to adverse effects of such pharmacotherapy cannot be understated.

Topics: Antipsychotic Agents; Chlorpromazine; Clozapine; Diabetes Mellitus; Humans; Hyperlipidemias; Long QT Syndrome; Myocarditis; Schizophrenia; Torsades de Pointes

Clozapine remains the most effective agent for treatment-resistant patients with schizophrenia. Recently, treatment with clozapine has been linked to a number of metabolic disturbances, including weight gain, diabetes mellitus, and serum lipid abnormalities. Despite the potential risks of medical morbidities, clozapine continues to have a major role in the care of treatment-resistant patients with schizophrenia. This article discusses the diagnosis and significance of the above metabolic abnormalities and potential mechanisms for these abnormalities as well as recommendations for monitoring and treatment.

Topics: Cholesterol; Clozapine; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Glucose Tolerance Test; Humans; Hyperlipidemias; Hypertriglyceridemia; Schizophrenia; Weight Gain

The available literature suggests that patients with schizophrenia are at risk for diabetes mellitus and taking antipsychotic medication further increases the chance of developing non-insulin-dependent hyperglycemia. Case reports, chart reviews, and some results from clinical drug trials implicate a relationship between glucose levels and treatment with clozapine or olanzapine in patients with schizophrenia, although a few cases of hyperglycemia have also been reported in patients taking risperidone and quetiapine. These studies indicate that hyperglycemia is not dose dependent, is reversible on cessation of treatment with clozapine or olanzapine, and reappears on reintroduction of these therapies. The postulated underlying mechanisms involved in this process in patients with schizophrenia include (1) a decreased sensitivity to insulin that is independent of atypical medication, (2) an increased insulin resistance related to atypical medications, (3) the effects of atypical medications on serotonin receptors, and (4) overuse of insulin due to weight gain. These mechanisms are discussed in detail, and recommendations for the administration of atypical antipsychotics are offered. Overweight, ethnicity, family or personal history of diabetes mellitus or hypertension, and weight gain during the course of treatment have all been identified as risk factors in the development of hyperglycemia in patients with schizophrenia. However, it is difficult to statistically assess the true incidence of diabetes within each type of antipsychotic medication group with the exclusive dependence on available case studies and without proper epidemiologic research.

Topics: Adolescent; Adult; Age Factors; Aged; Antipsychotic Agents; Benzodiazepines; Clozapine; Comorbidity; Diabetes Mellitus; Female; Humans; Hyperglycemia; Male; Middle Aged; Olanzapine; Pirenzepine; Prevalence; Risk Factors; Schizophrenia; United States

Hormonally related side effects of antipsychotic drugs, e.g. weight gain, hyperlipidemia and diabetes have come to the forefront in that the use of clozapine and new antipsychotics have increased. Hormones involved are prolactin, growth hormone (GH), insulin-like growth factor I (IGF-I), insulin and leptin. Patients treated with clozapine had lower levels of GH-dependent IGF-I than patients receiving classical antipsychotics. Patients treated with olanzapine had higher serum insulin levels than those receiving classical antipsychotics, indicating a probable influence of olanzapine on insulin secretion. In clozapine-treated patients the insulin levels correlated to the clozapine serum concentration, indicating a likely influence also of clozapine on insulin secretion. The gender difference, i.e. that women normally have higher leptin levels than men, was found in patients receiving classical antipsychotics, but not in patients treated with clozapine or olanzapine.

Topics: Antipsychotic Agents; Clozapine; Diabetes Mellitus; Female; Human Growth Hormone; Humans; Hyperlipidemias; Hyperprolactinemia; Insulin; Insulin-Like Growth Factor I; Lipids; Male; Prolactin; Weight Gain

The goal of this 5-year naturalistic study of patients treated with clozapine was to examine the incidence of treatment-emergent diabetes mellitus in relation to other factors, including weight gain, lipid abnormalities, age, clozapine dose, and treatment with valproate.. Data on age, gender, race, diagnosis, family history of diabetes, and age at clozapine initiation were collected from medical records of 82 outpatients with schizophrenia or schizoaffective disorder. Clozapine dose, data on use of valproate, and laboratory test results were recorded at 6-month intervals.. The mean age at the time of clozapine initiation of the 82 patients was 36.4 years; 26.8% of the patients were women, and 91.5% were Caucasian. The mean baseline weight was 175.5 lb, and the mean body mass index was 26.9 kg/m(2). Thirty patients (36.6%) were diagnosed with diabetes during the 5-year follow-up. Weight gain, use of valproate, and total daily dose of clozapine were not significant risk factors for developing diabetes mellitus. Patients experienced significant weight gain that continued until approximately month 46 from initiation of clozapine. There was a nonsignificant increase in total serum cholesterol and a significant increase in serum triglycerides level.. The results support the hypotheses that patients treated with clozapine experience significant weight gain and lipid abnormalities and appear to be at increased risk for developing diabetes.

Topics: Adult; Age Factors; Antipsychotic Agents; Body Mass Index; Body Weight; Cholesterol; Clozapine; Diabetes Mellitus; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Family; Female; Genetic Predisposition to Disease; Humans; Hypercholesterolemia; Hypertriglyceridemia; Incidence; Male; Obesity; Psychotic Disorders; Risk Factors; Schizophrenia; Triglycerides; Valproic Acid

Clozapine treatment for schizophrenia is typically long-term and is associated with a high rate of diabetes. Mental health and diabetes specialist teams at a local hospital in Australia have undertaken a series of joint specialist case conferences (JSCCs) where the diabetes team works with the psychiatry team to improve diabetes management. In this retrospective cohort study conducted between 2013 and 2018, we found that glycemic control in clozapine clinics linked with JSCCs was improved significantly compared with that in the non-JSCC clinics. In the non-JSCC clozapine clinics (control), the poor glycemic control rates stayed at a similar level: 23% in 2013 and 24% in 2018. In contrast, whereas the control patients' poor glycemic rate in JSCC clozapine clinics in 2013 was 24%, it decreased markedly in 2018 to 13%. This study indicates that JSCCs can improve diabetes outcomes in a group of patients with severe mental illness.

Topics: Antipsychotic Agents; Clozapine; Diabetes Mellitus; Humans; Retrospective Studies; Schizophrenia

Clozapine is a unique atypical anti-psychotic agent with best efficacy for treatment resistant schizophrenia compared to other agents, but with increased metabolic adverse effects. We sought to audit the prevalence of diabetes and pre-diabetes in Northland, New Zealand patients on clozapine.. We captured all 287 patients in Northland, New Zealand who were prescribed clozapine in September 2021 and obtained demographic, clinical and laboratory data.. We discovered that 26.48% had diabetes (one patient type one, 75 type two diabetes) and 14.63% had pre-diabetes that developed after a median of six years' clozapine treatment. Diabetes prevalence is approximately 6% in the general population. NZ Māori made up 65.85% of the entire cohort (35.8% of the general population) and 85.53% of the diabetes patients. NZ Europeans represented most of the remaining 30.66% on clozapine, consistent with the largely bicultural ethnic mix of our region. Māori on clozapine were younger: mean age 42 years, compared to NZ Europeans, mean age 49 years. The average BMI was 37kg/m2 for Māori, 32 for Europeans (range 21-63, SD 8); there was a moderate relationship between clozapine use and increasing BMI (correlation coefficient of 0.74). For the diabetes patients, glycaemic control was overall suboptimal with a mean Hba1c of 66mmol/mol (range 41-117).. Culturally appropriate, flexible and accessible services which integrate both the mental and physical health needs of Northland, New Zealand people with treatment-resistant schizophrenia on clozapine are required to reduce the 41% rate of dysglycaemia in this predominantly Māori group.

Topics: Adult; Clozapine; Diabetes Mellitus; Humans; Middle Aged; New Zealand; Prediabetic State; Prevalence; Schizophrenia

Reports of decreased mortality among patients with schizophrenia who use clozapine may be biased if clozapine is prescribed to relatively healthy patients and if intensive monitoring during its use prevents (under-treatment of) somatic disorder. We aimed to assess whether there is a difference in: (1) somatic comorbidity between patients who start with clozapine and those who start with other antipsychotics and (2) prescribed somatic medication, between patients using clozapine and those using olanzapine. Cohort study based on insurance claims (2010-2015). After selecting new users of antipsychotics and those who subsequently switched to clozapine (N = 158), aripiprazole (N = 295), olanzapine (N = 204) or first-generation antipsychotics (N = 295), we compared the clozapine starters to others on cardiovascular or diabetic comorbidity. Those using clozapine and olanzapine were compared on new prescriptions for cardiovascular or antidiabetic drugs. The ORadj of cardiovascular or diabetic comorbidity among other starters compared with clozapine starters was 0.77 [95% confidence interval (CI): 0.43-1.39], that is, a nonsignificantly increased prevalence associated with clozapine was found. Users of clozapine received significantly more new prescriptions for cardiovascular or antidiabetic medication (ORadj: 2.70, 95% CI: 1.43-5.08). Starters with clozapine were not cardiovascular/metabolic healthier than starters with other antipsychotics. During its use, they received more somatic treatment.

Topics: Aged; Antipsychotic Agents; Cardiovascular Agents; Cardiovascular Diseases; Clozapine; Diabetes Mellitus; Drug Administration Schedule; Drug Monitoring; Female; Health Status; Humans; Hypoglycemic Agents; Insurance Claim Review; Male; Middle Aged; Netherlands; Schizophrenia

Topics: Adolescent; Adult; Antipsychotic Agents; Clozapine; Diabetes Mellitus; Genetic Predisposition to Disease; Humans; Metabolic Syndrome; Middle Aged; Parents; Schizophrenia; Young Adult

Clozapine (CZ) is the most effective drug for managing treatment-resistant schizophrenic disorders. Its use has been limited due to adverse effects, which include weight gain and new-onset diabetes, but the incidence of these varies between patients.. We investigated 187 Clozapine Clinic patients (of whom 137 consented for genotyping) for the presence of CYP2C19*17 and its association with CZ and norclozapine (NCZ) levels, and clinical outcomes.. Thirty-nine percent of genotyped patients were carriers of the CYP2C 19*17 polymorphism. This group demonstrated significantly higher NCZ serum levels, and significantly lower fasting glucose (5.66 ± 1.19 vs 6.72 ± 3.01 mmol/l, P = 0.009) and Hb1Ac (35.36 ± 4.78 vs 49.40 ± 20.60 mmol/mol, P = 0.006) levels compared to non-carriers of this polymorphism. CZ-treated patients with CYP2C19*17/*17 had a significantly lower prevalence of diabetes as well as a higher likelihood of clinical improvement of their schizophrenia, compared to those without this polymorphism (P = 0.012 and P = 0.031, respectively).. Our data suggest that CYP2C19*17 ultra-rapid-metaboliser status is a protective factor against the development of diabetes during clozapine treatment, and increases the likelihood of improvement in schizophrenia. The role of NCZ in treatment response and side effects, including metabolic syndrome, warrants further pharmacogenetic, pharmacokinetic and pharmacodynamic studies.

Topics: Adult; Antipsychotic Agents; Clozapine; Cytochrome P-450 CYP2C19; Diabetes Mellitus; Female; Glycated Hemoglobin; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Protective Factors; Schizophrenia

Despite its superior efficacy, clozapine is an underutilized agent, primarily owing to the "Clozaphobia"-fear of clozapine's adverse effects. Emergent cautions on metabolic side-effects have contributed to avoidance of clozapine prescription. Here, we describe our clinical experience with nine patients having schizophrenia/schizoaffective disorders with comorbid diabetes mellitus and treated with clozapine. Interestingly, all patients could be maintained on optimal glycemic control even after clozapine. In conclusion, a critique on the potential risks versus benefits of clozapine amidst our observations from this case series adds further supporting evidence to the emerging literature on the clinical utility of clozapine in treating schizophrenia patients with diabetes mellitus.

Topics: Adult; Antipsychotic Agents; Clozapine; Comorbidity; Diabetes Mellitus; Female; Health Knowledge, Attitudes, Practice; Humans; Male; Middle Aged; Phobic Disorders; Psychotic Disorders; Schizophrenia

Constipation and dyspepsia are disturbing gastrointestinal symptoms that are often ignored in research on physical comorbidities of schizophrenia. The aim was to assess dyspepsia and constipation in a sample of outpatients with schizophrenia spectrum psychoses. A general practitioner performed a thorough physical health check for 275 outpatients and diagnosed constipation and dyspepsia. This study assessed the possible contribution of several sociodemographic, lifestyle, and clinical variables to constipation and dyspepsia using logistic regression analysis. This study also assessed whether these symptoms were associated with abnormal laboratory findings. The prevalence of constipation was 31.3%, and of dyspepsia 23.6%. Paracetamol (OR =3.07, 95% CI =1.34-7.02) and clozapine use (OR =5.48, 95% CI =2.75-10.90), older age (OR =1.04, 95% CI =1.01-1.06), and living in sheltered housing (OR =2.49, 95% CI =1.16-5.33) were risk factors for constipation. For dyspepsia the risk factors were female sex (OR =2.10, 95% CI =1.15-3.83), non-steroidal anti-inflammatory drugs (OR =2.47, 95% CI =1.13-5.39), and diabetes medication (OR =2.42, 95% CI =1.12-5.25). Patients with dyspepsia had lower haemoglobin and haematocrit and higher glucose values than those without dyspepsia. Patients with constipation had lower thrombocyte values than patients without constipation. However, these findings were explained by factors pre-disposing to constipation and dyspepsia. Clozapine use markedly increases the risk of constipation and may lead to life-threatening complications. In addition, analgesics and diabetes medication were related to gastrointestinal symptoms. These medications and their association to gastrointestinal symptoms should be kept in mind when treating patients with schizophrenia.

Topics: Adult; Analgesics; Antipsychotic Agents; Clozapine; Comorbidity; Constipation; Diabetes Mellitus; Dyspepsia; Female; Humans; Male; Schizophrenia

The authors compared the effectiveness of initiating treatment with either clozapine or a standard antipsychotic among adults with evidence of treatment-resistant schizophrenia in routine clinical practice.. U.S. national Medicaid data from 2001 to 2009 were used to examine treatment outcomes in a cohort of patients with schizophrenia and evidence of treatment resistance that initiated clozapine (N=3,123) and in a propensity score-matched cohort that initiated a standard antipsychotic (N=3,123). Interventions were new initiation of clozapine or a standard antipsychotic medication, defined as no exposure to the new medication in the prior 365 days. The primary outcome was hospital admission for a mental disorder. Secondary outcomes included discontinuation of the index antipsychotic, use of an additional antipsychotic, incidence of serious medical conditions, and mortality.. Initiation of clozapine was associated with a significantly decreased rate of psychiatric hospital admission (hazard ratio=0.78, 95% CI=0.69-0.88), index antipsychotic discontinuation (hazard ratio=0.60, 95% CI=0.55-0.65), and use of an additional antipsychotic (hazard ratio=0.76, 95% CI=0.70-0.82). Clozapine was associated with significantly increased incidence of diabetes mellitus (2.8% for clozapine vs. 1.4% for standard antipsychotic; hazard ratio=1.63, 95% CI=0.98-2.70), hyperlipidemia (12.9% for clozapine vs. 8.5% for standard antipsychotic; hazard ratio=1.40, 95%CI=1.09-1.78), and intestinal obstruction (0.9% for clozapine vs. 0.3% for standard antipsychotic; hazard ratio=2.50, 95% CI=0.97-6.44).. In adults with schizophrenia and evidence of treatment resistance, initiating clozapine compared with initiating a standard antipsychotic was associated with greater effectiveness on several important outcomes. Increasing the judicious use of clozapine is warranted together with vigilance to prevent and detect serious medical adverse effects.

Topics: Adult; Antipsychotic Agents; Clozapine; Cohort Studies; Databases, Factual; Diabetes Mellitus; Female; Hospitalization; Humans; Hyperlipidemias; Intestinal Obstruction; Logistic Models; Male; Medicaid; Mental Health Services; Middle Aged; Proportional Hazards Models; Psychotic Disorders; Retrospective Studies; Schizophrenia; Treatment Outcome; United States

To analyze antipsychotic prescribing patterns in a UK high security hospital (HSH) that treats seriously violent men with either schizophrenia or personality disorder and examine how different groups consented to treatment and prescribing for metabolic conditions. We hypothesized that there would be high prevalence of antipsychotic polypharmacy, and high-dose antipsychotic and clozapine prescribing.. HSHs treat seriously violent, mentally disordered offenders, and the extant literature on prescribing patterns in forensic settings is sparse.. Prescribing and clinical data on all 189 patients in a UK HSH were collected from the hospital's databases. Data were analyzed using SPSS.. The population was split into the following groups: schizophrenia spectrum disorder (SSD-only), personality disorder (PD-only), and comorbid schizophrenia spectrum disorder and PD. The majority (93.7%) of all patients were prescribed at least one antipsychotic, and (27.5%) were on clozapine. Polypharmacy was prevalent in 22.2% and high-dose antipsychotic in 27.5%. Patients on clozapine were more likely to be prescribed antidiabetic, statins, or antihypertensive medication. Patients in the PD-only group were more likely to be deemed to have the capacity to consent to treatment and be prescribed clozapine in contrast to the SSD-only group.. Rates of clozapine and high-dose antipsychotic prescribing were higher than in other psychiatric settings, while polypharmacy prescribing rates were lower. Higher clozapine prescribing rates may be a function of a treatment-resistant and aggressive population. A higher proportion of PD-only patients consented to treatment and received clozapine compared with in-house SSD-only as well as other psychiatric settings. Implications of the findings are discussed.

Topics: Adult; Antihypertensive Agents; Antipsychotic Agents; Clozapine; Criminals; Diabetes Mellitus; Dyslipidemias; Hospitals, Psychiatric; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Hypoglycemic Agents; Informed Consent; Male; Middle Aged; Personality Disorders; Polypharmacy; Practice Patterns, Physicians'; Psychotic Disorders; Schizophrenia; United Kingdom; Violence

Topics: Antipsychotic Agents; Clozapine; Diabetes Mellitus; Humans; Information Storage and Retrieval; Schizophrenia

Although many patients with schizophrenia fail to respond adequately to trials of 2 or more antipsychotics, utilization of clozapine for these patients remains low, despite recommendations for its use by accepted treatment guidelines. Some experts estimate that 5-10 times more patients could benefit from clozapine than who are now receiving it. Learning how to manage the unique side effect profile of clozapine can potentially remove barriers to prescribing this agent and thus unlock its unique therapeutic efficacy for more patients.

Topics: Agranulocytosis; Antipsychotic Agents; Clozapine; Constipation; Diabetes Mellitus; Eosinophilia; Humans; Myocarditis; Neuroleptic Malignant Syndrome; Neutropenia; Practice Guidelines as Topic; Practice Patterns, Physicians'; Schizophrenia; Sialorrhea; Tachycardia; Weight Gain

Compare long-term costs and outcomes of lurasidone to aripiprazole among adults with schizophrenia in the US who previously failed ≥1 atypical antipsychotic (olanzapine, risperidone, quetiapine, or ziprasidone) based on an indirect comparison of outcomes data from clinical trials.. A 5-year Markov cohort model was developed to compare long-term effectiveness of lurasidone to aripiprazole, including total discontinuations, relapse rates, and hospitalization rates. Cost inputs included pharmacy, mental health, and medical costs associated with cardiometabolic risks (diabetes and cardiovascular [CV] events). Effectiveness inputs were derived from an indirect comparison of aripiprazole and lurasidone using common comparators from CATIE. Cardiometabolic risks were derived from claims data analysis for diabetes, weight change and CV events, and Framingham body mass index (BMI) risk equation. Cost inputs were derived from published sources and Red Book. Costs and outcomes were discounted at 3% and tested with sensitivity analyses.. Over 5 years, total discounted costs for lurasidone and aripiprazole patients were $86,480 and $90,500, respectively. During this period, the number of relapses per patient, hospitalizations per patient, diabetes rates, and CV events per 1000 patients, respectively, were estimated to be lower for lurasidone (0.442, 0.245, 7.29%, and 37.3) than aripiprazole (0.478, 0.369, 7.36%, and 37.8). Results were sensitive to lurasidone and aripiprazole hospitalization rates. At a willingness-to-pay threshold of $50,000 per hospitalization avoided, lurasidone had a 100% probability of being more cost-effective than aripiprazole.. The model was based on results from various comparative clinical trials. Differences in patient population and study methods may change estimates from the model. The model does not account for patient heterogeneity.. Based on this model, when switching from another atypical antipsychotic, lurasidone had fewer relapses and hospitalizations with a lower incidence of diabetes and CV events than aripiprazole. Additionally, lurasidone may be less costly than aripiprazole among adults with schizophrenia.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Cardiovascular Diseases; Clinical Trials as Topic; Clozapine; Comorbidity; Cost-Benefit Analysis; Diabetes Mellitus; Hospitalization; Humans; Isoindoles; Lurasidone Hydrochloride; Markov Chains; Models, Economic; Outcome Assessment, Health Care; Piperazines; Quinolones; Recurrence; Schizophrenia; Thiazoles; United States

The use of clozapine and other antipsychotic drugs is known to be associated with a number of adverse metabolic side effects, including diabetes mellitus. These side effects could be, at least in part, the result of impaired islet cell function and abnormal insulin secretion, although the underlying mechanisms are unknown. The aim of this study is the identification of targets for clozapine related to the abnormal insulin secretion. We identify a specific activation of the transcriptional factor FOXA1, but not FOXA2 and FOXA3, by clozapine in HepG2 cells. Clozapine enhances FOXA1 DNA-binding and its transcriptional activity, increasing mitochondrial citrate carrier gene expression, which contains a FOXA1 site in its promoter. Haloperidol, a conventional antipsychotic drug, does not determine any increase of FOXA1 gene expression. We also demonstrate that clozapine upregulates FOXA1 and CIC gene expression in INS-1 cells only at basal glucose concentration. In addition, we find that abnormal insulin secretion in basal glucose conditions could be completely abolished by FOXA1 silencing in INS-1 cells treated with clozapine. The identification of FOXA1 as a novel target for clozapine may shed more light to understand molecular mechanism of abnormal insulin secretion during clozapine treatment.

Topics: Anion Transport Proteins; Antipsychotic Agents; Cell Line; Clozapine; Diabetes Mellitus; Gene Expression Regulation; Gene Silencing; Glucose; Haloperidol; Hep G2 Cells; Hepatocyte Nuclear Factor 3-alpha; Humans; Insulin; Insulin Secretion; Insulin-Secreting Cells; Mitochondrial Proteins; Organic Anion Transporters; Promoter Regions, Genetic; Recombinant Proteins; Response Elements; RNA, Messenger; RNA, Small Interfering; Up-Regulation

To examine the prevalence and correlates of diabetes in a large sample of Chinese patients with schizophrenia on long-term clozapine treatment, because this population previously has received little systematic study.. Two hundred and six inpatients meeting Diagnostic and Statistical Manual of Mental Disorders, 4th Edition schizophrenia criteria were recruited in a cross-sectional naturalistic study, and compared with 615 healthy control subjects matched for age, sex, education, and body mass index (BMI). The patient's psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). Diagnoses of diabetes were established through review of medical records and fasting blood glucose testing, or an oral glucose tolerance test.. Diabetes mellitus was more common in patients than in the normal controls (22.3% vs 6.2%) (odds ratio = 4.37, confidence interval (CI) 2.76-6.92, p < 0.001). The prevalence of diabetes increased with age across five age-groups as compared with normal controls (X(2) = 18.0, df = 4, p = 0.001). The PANSS total score and sub-scores showed no differences between the diabetic and non-diabetic groups. Logistic regression in the patients revealed significant associations between diabetes and a family history of diabetes (p < 0.001), age (p < 0.01), and BMI (p < 0.05).. Long-term clozapine treatment was associated with an increased and clinically important risk of diabetes mellitus in Chinese chronic schizophrenic patients, which is consistent with previous reports in Western populations.

Topics: Adult; Age Factors; Aged; Antipsychotic Agents; Blood Glucose; Body Mass Index; China; Chronic Disease; Clozapine; Cross-Sectional Studies; Diabetes Mellitus; Female; Glucose Tolerance Test; Humans; Logistic Models; Male; Middle Aged; Prevalence; Psychiatric Status Rating Scales; Risk Factors; Schizophrenia

To investigate the prevalence of and risk factors for overweight and diabetes mellitus in long-stay psychiatric inpatients.. Statistical analysis of data collected from medical, laboratory, and pharmacy files.. 80% of the 256 patients were suffering from schizophrenia or other psychotic disorders. The prevalence of diabetes mellitus was 15%. The prevalence of a disturbed glucose tolerance was 14%. Severe overweight (BMI > 30) was positively associated with the use of clozapine (odds ratio (OR) = 2.7; 95% confidence interval (CI): 1.31-5.75), but negatively with the diagnosis schizophrenia (OR = 0.4; 95% CI: 0.22-0.88). Diabetes mellitus was associated with severe overweight (OR = 3.5; 95% CI: 1.57-7.69). Caucasian patients were at a lower risk for diabetes mellitus (OR = 0.2; 95% CI: 0.08-0.54).. In residential psychiatric patients, diabetes mellitus is especially associated with overweight and non-Caucasian origin. In this survey, the use of clozapine was associated with overweight, but not directly with diabetes mellitus. Diabetes mellitus is highly prevalent, which calls for screening for diabetes mellitus at regular intervals.

Topics: Adult; Clozapine; Diabetes Mellitus; Ethnicity; Female; Glucose Intolerance; Humans; Inpatients; Male; Middle Aged; Obesity; Odds Ratio; Prevalence; Psychotic Disorders; Risk Factors; Schizophrenia

Topics: Antipsychotic Agents; Clozapine; Comorbidity; Diabetes Mellitus; Drug Monitoring; Humans; Metabolic Syndrome; Obesity; Psychotic Disorders; Risk Factors

The purpose of this study was to examine the association between atypical antipsychotics, including the newer agents, aripiprazole and ziprasidone, and newly treated diabetes, using the largest post-marketing cohort of patients exposed to these newer treatments that has been studied to date.. Identified two overlapping cohorts-a simple cohort (all antipsychotic users) and an inception cohort (new users of antipsychotics)-using automated data from three United States sites (60.4 million covered lives). Patients exposed to antipsychotics > or = 45 days were identified and followed for incident diagnoses of treated diabetes. Data analysis accounted for drug switching and non-consistent drug use.. In the 55 287-member inception cohort, 357 cases of newly treated diabetes were identified. Compared with current use of typical antipsychotics, current users of aripiprazole (adjusted hazard ratio (aHR) 0.93, 95% confidence interval (CI) 0.50-1.76), quetiapine (aHR 1.04, 95%CI, 0.67-1.62), risperidone (aHR 0.85, 95%CI, 0.54-1.36) and ziprasidone (aHR 1.05, 95%CI, 0.54-2.08) had similar low risk of diabetes. Patients exposed to olanzapine had an increased risk of diabetes (aHR 1.71, 95%CI, 1.12-2.61), and although the effect estimate is imprecise, clozapine-exposed patients had a trend towards an elevated hazard ratio (aHR 2.58, 95%CI, 0.76-8.80). Results for the simple cohort were similar.. Relative to typical antipsychotics, aripiprazole, ziprasidone, risperidone and quetiapine were not associated with an increased risk of diabetes; olanzapine and clozapine were associated with an increased risk. This analysis constitutes the largest post-marketing pharmacoepidemiologic study to date that includes the newer agents.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Cohort Studies; Diabetes Mellitus; Female; Humans; Male; Mental Disorders; Middle Aged; Olanzapine; Piperazines; Quinolones; Retrospective Studies; Thiazoles; United States

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Diabetes Mellitus; Diabetic Ketoacidosis; Dibenzothiazepines; Humans; Mass Screening; Olanzapine; Piperazines; Predictive Value of Tests; Prospective Studies; Quetiapine Fumarate; Quinolones; Severity of Illness Index

Topics: Alcoholism; Amisulpride; Antipsychotic Agents; Behavior, Addictive; Blood Glucose; Clozapine; Comorbidity; Diabetes Mellitus; Diagnosis, Dual (Psychiatry); Drug Therapy, Combination; Humans; Male; Middle Aged; Schizophrenia; Sulpiride

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

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

Previous research has suggested an association between use of atypical antipsychotics and onset of diabetes mellitus. We sought to compare the incidence of new onset diabetes among patients receiving atypical antipsychotics, traditional antipsychotics or antidepressants.. Retrospective cohort study of outpatients with claims for atypical antipsychotics (n = 10 265) compared to controls with claims for traditional antipsychotics (n = 4607), antidepressants (n = 60 856) or antibiotics (n = 59 878) in the administrative claims database of a large pharmaceutical benefit manager between June 2000 and May 2002. Main outcome measures were adjusted and unadjusted incidence rates of diabetes (new cases per 1000 per year) in a 12-month period, as measured using new prescriptions for antidiabetic drugs after a 6-month lead-in period.. Annual unadjusted incidence rates of diabetes (new cases per 1000 per year) were 7.5 for atypical antipsychotics, 11.3 for traditional antipsychotics, 7.8 for antidepressants and 5.1 for antibiotics. In multivariable analyses, age, male sex and Chronic Disease Score were associated with greater odds of diabetes onset. There were no statistically significant differences in outcome between the atypical antipsychotic, traditional antipsychotic and antidepressant groups. Multivariable comparisons among specific agents showed increased odds of diabetes for clozapine, olanzapine, ziprasidone and thioridazine (relative to risperidone), but these comparisons did not reach statistical significance.. In a large prescription claims database, outpatients taking atypical antipsychotics did not have higher rates of diabetes onset, compared to subjects taking traditional antipsychotics or antidepressants.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Clozapine; Cohort Studies; Databases, Factual; Diabetes Mellitus; Dibenzothiazepines; Drug Prescriptions; Female; Humans; Incidence; Insurance Claim Reporting; Male; Middle Aged; Multivariate Analysis; Olanzapine; Outpatients; Piperazines; Quetiapine Fumarate; Retrospective Studies; Risperidone; Sex Factors; Thiazoles; Thioridazine; Time Factors; United States

This retrospective study compared the prevalence of diabetes mellitus/hyperglycemia between patients receiving treatment with clozapine (n = 24) and patients receiving treatment with depot (n = 27) neuroleptics in a Department of Veterans Affairs outpatient mental health clinic in the Mid-Atlantic region. Of the clozapine cases without a history of diabetes/hyperglycemia, 27.7% developed diabetes after initiation of clozapine. There were no new cases of diabetes/hyperglycemia in the depot group after initiation of depot neuroleptic. All patients receiving neuroleptic treatment should be monitored for changes in weight, lipid, and glucose levels so that appropriate preventive and therapeutic measures can be promptly initiated.

Topics: Adult; Antipsychotic Agents; Body Weight; Clozapine; Delayed-Action Preparations; Diabetes Mellitus; Drug Monitoring; Female; Health Services Needs and Demand; Humans; Hyperglycemia; Male; Mass Screening; Mid-Atlantic Region; Middle Aged; Nurse's Role; Prevalence; Retrospective Studies; Risk Factors; Schizophrenia; United States; United States Department of Veterans Affairs; Veterans

The purpose of this study is to determine sociodemographic, clinical, and pharmacotherapeutic characteristics, especially use of atypical antipsychotics, associated with incident diabetes mellitus in a population of privately insured patients with mental health diagnoses. Patients with a mental health diagnosis stably medicated for a 3-month period during January 1999 through October 2000 and having no diabetes were followed through December 2000. Cox proportional hazards models were developed to identify antipsychotic medications associated with newly diagnosed diabetes. Of the 7381 patients identified, 339 developed diabetes, representing an annual incidence rate of 4.7%. Diabetes risk among the entire sample was lowest for risperidone (hazard ratio [HR] = 0.69; p < 0.05), while quetiapine (HR = 0.74), olanzapine (HR = 0.95), and clozapine (HR = 1.22) were not significantly different from first-generation antipsychotics. Diabetes risk was significantly lower among males receiving risperidone (HR = 0.49; p < 0.01) or quetiapine (HR = 0.50; p < 0.10), while diabetes risk among females did not differ significantly from first-generation antipsychotics for any atypical examined. These findings are substantially different from other reports.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Diabetes Mellitus; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Incidence; Insurance Coverage; Male; Mental Disorders; Olanzapine; Proportional Hazards Models; Quetiapine Fumarate; Risk Factors; Risperidone; Sex Factors; United States

Treatment with antipsychotic drugs has been associated with increased risk for developing diabetes mellitus. Recent consensus statements suggest that clozapine may pose an especially high risk. The purpose of this study is to examine the prevalence and clinical-demographic correlates of diabetes among outpatients with DSM-IV-diagnosed schizophrenia or schizoaffective disorder receiving clozapine.. One hundred one outpatients receiving clozapine at the University of Rochester Department of Psychiatry, Rochester, N.Y., were evaluated between September 2002 and September 2003. Demographic data were collected from medical records, and body mass index (BMI) and body fat measurements were conducted. Diagnosis of diabetes was established through review of medical records and fasting blood glucose testing. Associations between clinical and demographic variables and diabetes were examined using t tests, Fisher exact tests, and logistic regression.. Mean (SD) age of patients was 40.4 (9.5) years, and 79% were white. Mean (SD) dose and duration of clozapine treatment were 426 (164) mg/day and 5.7 (3.6) years, respectively. Point prevalence of diabetes was 25.7%. Mean (SD) BMI was 32.6 (8.0) kg/m(2), and mean (SD) body fat was 34.0% (11.0%). Logistic regression revealed significant associations between diabetes and nonwhite race/ethnicity and family history of diabetes (p = .02 and .002, respectively). No significant associations were found between diabetes prevalence and BMI or body fat.. Patients receiving clozapine are at substantial risk for developing diabetes, although the level of risk relative to other antipsychotic medications has not been fully determined. Clinicians should monitor all severely mentally ill patients receiving antipsychotic drugs for diabetes, with closer monitoring of patients with established demographic risk factors.

Topics: Adipose Tissue; Adolescent; Adult; Ambulatory Care; Antipsychotic Agents; Blood Glucose; Body Mass Index; Clozapine; Diabetes Mellitus; Diagnostic and Statistical Manual of Mental Disorders; Drug Administration Schedule; Female; Humans; Male; Middle Aged; New York; Prevalence; Psychiatric Status Rating Scales; Psychotic Disorders; Risk Factors; Schizophrenia; Sex Factors

The goal of this 10-year naturalistic study was to examine, in clozapine-treated patients, the change in cardiovascular risk factors following clozapine initiation and the mortality estimates from cardiovascular disease.. Data were collected from medical records from January 1992 to December 2003 and included age, gender, race, diagnosis, family history of diabetes, and age at clozapine initiation for clozapine-treated patients with schizophrenia or schizoaffective disorder (DSM-IV criteria). Clozapine dosage and laboratory results were recorded at 12-month intervals.. At the time of clozapine initiation, the mean +/-?SD age of the 96 patients studied was 36.5 +/- 7.9 years; 28% (N = 27) were women. The Kaplan-Meier estimate for 10-year mortality from cardiovascular disease was 9%. African American and Hispanic American patients exhibited elevated risk of cardiovascular disease-related mortality (odds ratio [OR] = 7.2, p = .09; OR = 11.3, p = .04, respectively) compared to white patients. Body mass index (BMI) significantly increased the odds ratio of mortality (OR = 1.2, p < .01). The Kaplan-Meier estimate for new-onset diabetes mellitus was approximately 43%, and Hispanic American (OR = 4.3, p = .027) and African American (OR = 11.5, p = .0001) patients showed elevated risks of developing diabetes mellitus compared to white patients. Additionally, BMI (OR = 1.11, p = .0006), total cholesterol level (OR = 1.006, p = .04), and serum triglyceride level (OR = 1.002, p = .04) modestly increased the odds ratio for the development of diabetes mellitus.. These results support the hypothesis that clozapine-treated patients appear to be at risk for death from cardiovascular disease secondary to clozapine-associated medical disorders such as obesity, diabetes, hypertension, and hyperlipidemia.

Topics: Adult; Antipsychotic Agents; Black or African American; Cardiovascular Diseases; Cause of Death; Clozapine; Comorbidity; Diabetes Mellitus; Female; Hispanic or Latino; Humans; Hyperlipidemias; Longitudinal Studies; Male; Metabolic Syndrome; Psychotic Disorders; Risk Factors; Risperidone; Schizophrenia; Survival Analysis

The use of atypical antipsychotics has been associated with abnormalities of glucose metabolism in patients with schizophrenia. This study was designed to determine the proportion of undiagnosed hyperglycemia in patients receiving a broad range of atypical antipsychotics.. All outpatients treated at an urban Veterans Affairs medical center who received a prescription for clozapine, risperidone, olanzapine, quetiapine, or ziprasidone were identified, and an attempt was made to obtain a fasting plasma glucose (FPG) test. Testing took place October 2000 to November 2002. Patients previously diagnosed as diabetic were excluded.. Of the 647 patients who received antipsychotic prescriptions and were not diagnosed as diabetic, 494 (76.4%) had a random glucose result, while 153 (23.6%) had an FPG result. Within the FPG group, 107 (69.9%) had a normal FPG level, while 46 (30.1%) had an abnormally elevated FPG. There were no differences between these 2 groups in terms of race/ethnicity, age, body mass index, or comorbid diagnoses. However, significantly more patients receiving clozapine were found to have occult hyperglycemia (p = .001); no significant differences in the percentage of patients with FPG levels > or = 100 mg/dL and those with FPG levels < 100 mg/dL were observed for any of the other medications.. Hyperglycemia is common in patients treated with atypical antipsychotics and thought to be euglycemic. Screening for elevated FPG is indicated for patients receiving atypical antipsychotics.

Topics: Ambulatory Care; Antipsychotic Agents; Blood Glucose; Clozapine; Comorbidity; Connecticut; Diabetes Mellitus; Drug Therapy, Combination; Female; Glucose Tolerance Test; Hospitals, Veterans; Humans; Hyperglycemia; Male; Mass Screening; Mental Disorders; Middle Aged; Sampling Studies; Schizophrenia

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Diabetes Mellitus; Dibenzothiazepines; Female; Humans; Incidence; Male; Middle Aged; Olanzapine; Quetiapine Fumarate; Retrospective Studies; Risperidone

Understanding the association between use of antipsychotics and onset of diabetes.. To compare the rates of new-onset diabetes mellitus (DM) between patients treated for schizophrenia with atypical or conventional antipsychotics.. Retrospective analysis of medical and pharmacy claims data.. 61 US health plans.. Patients with schizophrenia who were treated with atypical or conventional antipsychotics between September 1996 and June 2001 and were enrolled for 12 or more months before and 3 or more months after therapy initiation.. New-onset DM was defined based on 2 or more claims with a diabetes diagnosis or initiation of antidiabetic therapy during follow-up. Rates of DM were compared between patients receiving atypical and conventional antipsychotics, and among 4 subgroups of patients receiving atypical antipsychotics (olanzapine, clozapine, risperidone, quetiapine). Statistical analyses employed logistic regression and Cox proportional hazards models.. Patients treated with atypical antipsychotics (N = 1826) were younger, had a lower rate of diagnosed hypertension, and longer duration of therapy than those receiving conventional antipsychotics (N = 617). The crude incidence of DM did not differ (2.46% vs 2.76% for atypical antipsychotics and conventional antipsychotics, P =.525). In Cox proportional hazards models, patients treated with atypical antipsychotics had a statistically significant, moderately increased risk of DM relative to conventional antipsychotics (hazard ratio [HR] = 1.17, 95% confidence interval [CI] = 1.06, 1.30); no significant differences in risk were observed when atypical antipsychotic cohorts were compared. In logistic regression models, no significant differences in DM risk were observed.. Patients with schizophrenia treated with atypical antipsychotics had a moderately increased risk of DM relative to those treated with conventional antipsychotics, as measured by Cox proportional hazards models; such risk was not significantly different among patients treated with individual atypical medications.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Diabetes Mellitus; Dibenzothiazepines; Female; Humans; Incidence; Male; Managed Care Programs; Olanzapine; Patient Selection; Quetiapine Fumarate; Retrospective Studies; Risperidone; Schizophrenia

The purpose of the study was to determine the proportion of patients with schizophrenia with a stable regimen of antipsychotic monotherapy who developed diabetes or were hospitalized for ketoacidosis.. Patients with schizophrenia for whom a stable regimen of antipsychotic monotherapy was consistently prescribed during any 3-month period between June 1999 and September 2000 and who had no diabetes were followed through September 2001 by using administrative data from the Department of Veterans Affairs. Cox proportional hazards models were developed to identify the characteristics associated with newly diagnosed diabetes and ketoacidosis.. Of the 56,849 patients identified, 4,132 (7.3%) developed diabetes and 88 (0.2%) were hospitalized for ketoacidosis. Diabetes risk was highest for clozapine (hazard ratio=1.57) and olanzapine (hazard ratio=1.15); the diabetes risks for quetiapine (hazard ratio=1.20) and risperidone (hazard ratio=1.01) were not significantly different from that for conventional antipsychotics. The attributable risks of diabetes mellitus associated with atypical antipsychotics were small, ranging from 0.05% (risperidone) to 2.03% (clozapine).. Although clozapine and olanzapine have greater diabetes risk, the attributable risk of diabetes mellitus with atypical antipsychotics is small.

Topics: Ambulatory Care; Antipsychotic Agents; Benzodiazepines; Clozapine; Diabetes Mellitus; Diabetic Ketoacidosis; Dibenzothiazepines; Hospitalization; Humans; Incidence; Olanzapine; Proportional Hazards Models; Quetiapine Fumarate; Risk Factors; Risperidone; Schizophrenia; United States

This study examined data on patients with serious and persistent mental illness in a large state hospital system to determine whether patients who took second-generation antipsychotics were more likely to develop diabetes mellitus than patients who took first-generation antipsychotics.. A case-control study design was used. A new prescription of an antidiabetic medication was used to identify new cases of diabetes mellitus. Odds ratios were calculated for exposure to second-generation antipsychotics (clozapine, risperidone, olanzapine, quetiapine, and multiple second-generation antipsychotics) compared with exposure to first-generation antipsychotics. Cases and controls were identified by using a database that contained drug prescription information from the inpatient facilities that were operated by the New York State Office of Mental Health. Data from January 1, 2000, to December 31, 2002, were examined. Among 13,611 unique patients who received antipsychotics, 8,461 met entry criteria of being hospitalized for at least 60 days and not having an antidiabetic medication prescribed in the past. A total of 181 of these inpatients received prescriptions for an antidiabetic medication at least 30 days after their admission. Eight controls (N=1,448) for each case (N=181) were matched by calendar year, length of observation period, race, age group, and diagnosis, giving a total sample of 1,629 patients.. Statistically significant elevations in risk were seen among patients who received more than one second-generation antipsychotic or clozapine or quetiapine, compared with patients who received first-generation antipsychotics alone. Although not statistically significant, odds ratios for olanzapine and risperidone were also elevated. Conditional logistic regression adjusting for gender and age did not change the results.. Exposure to multiple second-generation antipsychotics or clozapine or quetiapine significantly increased the risk of treatment-emergent diabetes mellitus.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Case-Control Studies; Clozapine; Demography; Diabetes Mellitus; Dibenzothiazepines; Female; Humans; Hypoglycemic Agents; Male; Olanzapine; Quetiapine Fumarate; Risperidone; Schizophrenia; Sex Factors

Clozapine is the gold standard treatment for Parkinson's disease (PD) psychosis based on double blinded, placebo controlled trials, and has also been shown to alleviate tremor and dyskinesia. There is accumulating data suggesting that clozapine may be associated with increased frequency of diabetes mellitus (DM) compared to conventional neuroleptic drugs in treating schizophrenia. Forty-four predominantly geriatric parkinsonian subjects on clozapine for psychosis, tremor or dyskinesia, on an average dose of 50.6 mg/d for a mean duration of 41 months were reviewed. The prevalence of DM in this cohort was 18.1% (8/44). This rate was similar to that reported in the aged-matched general population (prevalence = 19.3% for ages > or = 60 years). In this small study, parkinsonian patients on long-term, low dose clozapine were not at increased risk for developing DM. Larger controlled prospective studies are needed to confirm this.

Topics: Adult; Aged; Antipsychotic Agents; Clozapine; Cohort Studies; Dementia; Diabetes Mellitus; Female; Humans; Male; Middle Aged; Parkinson Disease

Topics: Antipsychotic Agents; Clozapine; Diabetes Mellitus; Dyskinesia, Drug-Induced; Humans; Patient Compliance; Schizophrenia; Weight Gain

Information from the Ohio Department of Mental Health (ODMH) database was reviewed retrospectively to identify patients at the Cincinnati center treated with an atypical antipsychotic and who had also been evaluated or treated for diabetes mellitus. Blood glucose levels, glucose tolerance, or other evaluations of diabetes had been conducted in 14 of the 126 patients treated with atypical antipsychotics. In 11 of the 14, new-onset, acute, and marked glucose intolerance developed after treatment with clozapine, olanzapine or quetiapine. Of these, six patients required insulin therapy (four only transiently) and five patients developed diabetic ketoacidosis (DKA). Also, glucose metabolism was labile in all cases, and was transient in two cases with subsequent resolution despite on-going antipsychotic therapy. Certain atypical antipsychotics may be associated with new-onset glucose intolerance, including acute diabetes and ketoacidosis. Monitoring for changes in blood glucose levels in patients taking atypical antipsychotics may be indicated. More systematic study data are clearly needed.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Diabetes Mellitus; Diabetic Ketoacidosis; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Ohio; Olanzapine; Pirenzepine; Quetiapine Fumarate; Retrospective Studies

Clozapine has been demonstrated to be superior to typical neuroleptics in reducing refractory symptoms in patients with schizophrenia, but it has also been associated with hyperglycemia and diabetes mellitus. This study was designed to investigate the proportion of undiagnosed impaired fasting glucose and diabetes mellitus in patients prescribed clozapine at 8 Department of Veterans Affairs (VA) medical centers.. All patients diagnosed by the VA in New England with ICD-9 schizophrenia from Oct. 1, 1999, to Sept. 30, 2000, who received a prescription for clozapine were identified, and an attempt was made to obtain a fasting plasma glucose (FPG) test. All patients were also characterized as to whether they were diagnosed as diabetic prior to the screening FPG. Patients not previously diagnosed as diabetic were divided into 2 groups: normal FPG (< 110 mg/dL) and elevated FPG (>or= 110 mg/dL). Clinical and sociodemographic characteristics of the 2 groups were compared using chi-square and t tests.. Overall, 121 patients were not previously diagnosed as diabetic and received an FPG. Ninety-three (77%) had a normal FPG, and 28 (23%) had an elevated plasma glucose-including 17% with impaired fasting glucose and 6% with diabetes. Patients with hyperglycemia were significantly older (p =.007) and more commonly codiagnosed with bipolar disorder (p =.04).. Hyperglycemia was common in patients receiving clozapine who had not been previously diagnosed as diabetic. These patients should be considered a group at high risk to develop diabetes mellitus and deserve both close monitoring and early intervention at the first sign of the onset of either diabetes or impaired glucose tolerance.

Topics: Antipsychotic Agents; Blood Glucose; Body Mass Index; Clozapine; Diabetes Mellitus; Female; Glucose Tolerance Test; Humans; Hyperglycemia; Male; Middle Aged; New England; Risk Factors; Schizophrenia

Issues to consider when evaluating maintenance drug therapy for patients with schizophrenia are discussed; these include potential adverse effects of antipsychotic therapy, such as weight gain, diabetes mellitus, extrapyramidal symptoms, sexual dysfunction, cognitive dysfunction, and cardiac effects, as well as quality of life. Patients with schizophrenia are more likely to be overweight than the general population. Olanzapine and clozapine have been associated with the greatest weight gain of the newer antipsychotics. While patients with schizophrenia are at increased risk of developing diabetes mellitus independent of antipsychotic therapy, diabetes may be more prevalent in patients taking the newer agents. Acute extrapyramidal symptoms occur in 75-90% of patients receiving first-generation antipsychotics like thioridazine and haloperidol. The probability of tardive dyskinesia (TD) occurring with second- and third-generation agents is less than 1% per year, compared with about 5% per year for the traditional antipsychotics. When patients are switched from a traditional antipsychotic to clozapine or olanzapine, TDs usually abate somewhat. Thioridazine causes a pronounced prolongation of the QTc interval, which can lead to ventricular arrhythmias. The slight increase in QTc interval caused by ziprasidone most likely will not be a problem in healthy individuals. Newer antipsychotics are associated with improved neurocognitive functioning and most cause less prolactin elevation, compared with traditional agents. The newer antipsychotic agents are not devoid of adverse effects, but those that do occur can be managed. Once issues related to adherence are resolved, rehabilitation of patients with schizophrenia will be a high priority.

Topics: Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Clozapine; Continuity of Patient Care; Diabetes Mellitus; Electrocardiography; Humans; Movement Disorders; Olanzapine; Pirenzepine; Quality of Life; Schizophrenia; Weight Gain

Previous studies have suggested that the atypical antipsychotics clozapine and olanzapine may be associated with an increased risk of glucose intolerance and diabetes mellitus. Early studies have also suggested an association between use of conventional antipsychotics and the development of glucose intolerance.. To examine quantitatively the association between glucose intolerance including diabetes mellitus and the use of the atypical antipsychotics clozapine, olanzapine or risperidone, and to identify possible risk factors for the development of glucose intolerance during treatment with these drugs.. All reports suggestive of glucose intolerance for clozapine, olanzapine and risperidone were identified in the WHO database for adverse drug reactions. In the analyses of possible risk factors for glucose intolerance all other reports of adverse drug reactions for clozapine, olanzapine and risperidone were used as reference. Using the Bayesian Confidence Propagation Neural Network method, the strengths of the associations over time between glucose intolerance and the use of these drugs were analysed. For comparison, the strengths of the associations between glucose intolerance and the use of the conventional antipsychotics haloperidol and chlorpromazine were also analysed.. Clozapine, olanzapine and risperidone were significantly associated with glucose intolerance. In contrast, chlorpromazine and haloperidol were not associated with glucose intolerance. For clozapine, olanzapine and risperidone grouped together, the following potential risk factors for glucose intolerance were identified: an underlying diabetic condition (odds ratio [OR] 10.22, 95% CI 8.20-12.73), an increase in weight (OR 2.36, 95% CI 1.76-3.17), male gender (OR 1.27, 95% CI 1.11-1.47), and concomitant use of valproic acid (OR 1.97, 95% CI 1.61-2.40), selective serotonin reuptake inhibitors (OR 1.63, 95% CI 1.33-1.99) or buspirone (OR 2.24, 95% CI 1.33-3.77).. Treatment with clozapine, olanzapine or risperidone appears to be associated with an increased risk of glucose intolerance.

Topics: Adverse Drug Reaction Reporting Systems; Antipsychotic Agents; Bayes Theorem; Benzodiazepines; Chlorpromazine; Clozapine; Diabetes Mellitus; Glucose Intolerance; Haloperidol; Humans; Hyperglycemia; Olanzapine; Pirenzepine; Risk Factors; Risperidone; World Health Organization

Recent reports have raised the concern that clozapine increases the risk for diabetes mellitus. Accurate pharmacoepidemiologic data on whether such a hazard exists and its magnitude are needed to enable clinicians and patients to make proper treatment decisions about clozapine. The authors performed a case-control study involving 7,227 cases of newly treated diabetes and 6,780 controls, all with psychiatric disorders. Cases and controls were older than 20 years and enrolled in government-sponsored drug benefit programs in New Jersey. The authors measured the use of clozapine or other antipsychotic medications and additional covariates. They developed logistic regression models adjusted for demographic, clinical, and health care use characteristics to identify whether clozapine users were at increased risk to begin treatment for diabetes. Clozapine use was not significantly associated with developing diabetes (adjusted odds ratio [OR], 0.98; 95% confidence interval [CI], 0.74-1.31). There was no suggestion of relationships between larger dosages or longer durations of clozapine use and increasing risks of diabetes. On the other hand, nonclozapine antipsychotic medication use was associated with a modest but significantly increased risk of developing diabetes (adjusted OR, 1.13; 95% CI, 1.05-1.22). Among individual nonclozapine antipsychotics, significantly elevated risks were observed for two phenothiazine agents: chlorpromazine (adjusted OR, 1.31; 95% CI, 1.09-1.56) and perphenazine (adjusted OR, 1.34; 95% CI, 1.11- 1.62). In contrast to earlier reports, these results provide some reassurance that clozapine does not increase the risk of developing diabetes. Additional data from pharmacoepidemiologic studies and randomized controlled trials are needed to exclude the possibility of residual confounding and ensure the appropriate use of this agent.

Topics: Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Case-Control Studies; Clozapine; Confidence Intervals; Diabetes Mellitus; Dose-Response Relationship, Drug; Female; Humans; Logistic Models; Male; Middle Aged; Odds Ratio; Risk Factors

Clozapine is a potent antipsychotic agent that has been marketed since 1990. Several published reports of diabetes mellitus occurring with clozapine therapy have appeared during the past 5 years. Because the risk and characteristics of clozapine-associated diabetes mellitus remain unclear, we conducted a descriptive epidemiologic study of spontaneous adverse event reports of hyperglycemia occurring in clozapine-treated patients. The Food and Drug Administration MedWatch surveillance program was queried (January 1990 through February 2001), and the results were pooled with published cases. Parameters assessed included documentation of diabetes, clinical severity, new-onset diabetes versus exacerbation of preexisting disease, demographic characteristics of patients, time to onset of hyperglycemia, and effect of drug discontinuation and rechallenge. We identified 384 reports. Of these, new-onset diabetes was diagnosed definitively in 242 patients, and 54 patients had exacerbation of preexisting disease. The mean (+/- SD) age was 40 +/- 12 years (range, 13 to 77). The male:female ratio was 2:0. Most cases appeared within 6 months of initiating clozapine therapy. One patient developed diabetes following a single 500-mg dose. There were 80 cases of metabolic acidosis or ketosis. Twenty-five patients died during hyperglycemic episodes. Forty-six patients had improved glycemic control after discontinuation or dose reduction of the drug.A causal relationship between clozapine and diabetes is suggested by the number of reports, the temporal relation to clozapine initiation, the relatively young age of the affected patients, and the prompt reversibility on withdrawal of the drug in some patients. The severity of reported cases ranged from mild glucose intolerance to diabetic ketoacidosis or hyperosmolar coma.

Topics: Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Age Distribution; Aged; Antipsychotic Agents; Clozapine; Diabetes Mellitus; Female; Humans; Male; Middle Aged; Risk Factors; Time Factors

Clozapine is an atypical antipsychotic that is associated with certain adverse effects that limit its usefulness. Published case reports have associated clozapine with impairment of glucose tolerance, including the onset or exacerbation of diabetes mellitus. We report two patients who experienced diabetes mellitus associated with the agent.

Topics: Antipsychotic Agents; Chronic Disease; Clozapine; Diabetes Mellitus; Female; Glucose Tolerance Test; Humans; Middle Aged; Schizophrenia

Atypical anti-psychotic drugs (APDs) are widely used in psychotic disorders refractory to conventional neuroleptic agents.. Three cases of new-onset diabetes are reported in Caucasian men who were on clozapine (one) or olanzapine (two) for 3-6 months. They had a distinct presentation: weight loss, ketosis (one ketoacidosis), severe hyperglycaemia requiring insulin therapy, and relative insulin deficiency as reflected by glucagon stimulatory tests. In all cases, insulin was stopped within 1 month after the APD was discontinued.. Novel APDs not only induce diabetes as a result of weight gain in predisposed patients, but can also lead to a reversible state of insulin deficiency, and sometimes ketoacidosis.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Depressive Disorder; Diabetes Mellitus; Glyburide; Humans; Hypoglycemic Agents; Insulin; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Schizophrenia

Recent case reports suggest the association of the emergence of diabetes mellitus with clozapine treatment, although conventional neuroleptics have also been implicated. This study was conducted to determine if there is an increased risk of diabetes mellitus and/or impaired glucose tolerance (IGT) during clozapine treatment compared with treatment with conventional depot neuroleptics.. In a district hospital in northern Sweden, blood glucose tests and, if necessary an oral glucose tolerance test were used to assess the prevalence of diabetes mellitus or IGT in 63 patients treated with clozapine compared with 67 patients treated with conventional depot neuroleptics (haloperidol, zuclopenthixol, fluphenazine, perphenazine, or flupenthixol). Diabetes mellitus and impaired glucose tolerance were classified according to World Health Organization criteria.. There were 3 dropouts in the clozapine group and 4 in the control group. Of subjects treated with clozapine, 12% (7/60) had type 2 diabetes mellitus, and 10% (6/60) had IGT. Of subjects treated with depot injections of neuroleptics, 6% (4/63) had type 2 diabetes mellitus and 3% (2/63) had IGT. None in either group had type 1 diabetes mellitus. Subjects in the clozapine group were significantly (p < .001) younger than subjects in the control group, whereas the 2 groups did not differ with respect to body weight, body mass index, or prevalence of diabetes mellitus in first-degree relatives.. Subjects treated with clozapine were more often classified as having type 2 diabetes mellitus or IGT compared with subjects in the control group. This difference did not, however, achieve statistical significance (p=.06).

Topics: Adult; Aged; Antipsychotic Agents; Blood Glucose; Clozapine; Comorbidity; Delayed-Action Preparations; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glucose Tolerance Test; Humans; Male; Mental Disorders; Middle Aged; Prevalence; Schizophrenia; Sweden

Clozapine is an effective therapy for the treatment of refractory psychosis. Clozapine-associated adverse effects include sedation, weight gain, sialorrhea, palpitations, seizures, and hematologic changes such as agranulocytosis.. We present a four-case series in which clozapine use was associated with either a de novo onset or severe exacerbation of preexisting diabetes mellitus.. The change in glycemic control was not significantly related to weight gain. Three of the patients have been able to continue on clozapine therapy and have experienced a reduction in psychotic symptoms.. Patients with a family history of diabetes mellitus or with preexisting diabetes mellitus may need to have blood sugar monitored closely during initiation of clozapine treatment.

Topics: Adult; Blood Glucose; Clozapine; Comorbidity; Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Intolerance; Humans; Hyperglycemia; Male; Middle Aged; Psychotic Disorders; Randomized Controlled Trials as Topic; Schizophrenia; Treatment Outcome