clozapine and Dyslipidemias

Schizophrenia, a serious psychiatric disorder, is among the top 10 global causes of disability and affects nearly 1% of the world population. Antipsychotics constitute the best treatment for patients with schizophrenia, however, this treatment class carries a high risk of metabolic syndrome, including lipid abnormalities. Indeed, the risk of metabolic syndrome would be increased in the population with schizophrenia compared to the general population. The objective is to summarize the prevalence, the mechanisms, and the potential treatments of antipsychotic-induced metabolic syndrome. This is a narrative review of the literature. We searched the electronic database Medline, accessed through PubMed, to find studies that investigated the prevalence and treatments of metabolic syndrome in the adult population using antipsychotics. The prevalence of metabolic syndrome in patients treated with antipsychotics ranges from 37% to 63%. Antipsychotic iatrogenic effects include weight gain/increased waist circumference, dyslipidemia, insulin resistance/type 2 diabetes, and hypertension. Clozapine and olanzapine are reported to precipitate the onset of metabolic syndrome features. In patients with metabolic syndrome, an antipsychotic with less metabolic side effects such as lurasidone, lumateperone, ziprasidone, and aripiprazole should be prioritized. Unlike medications, aerobic exercise and dietetic counseling were found to be efficient as the nonpharmacologic treatment of antipsychotic-induced metabolic syndrome. Few pharmacological treatments were proven effective against weight gain in this patient population. The risk of metabolic syndrome induced by antipsychotics should be early recognized and closely monitored. Primary and secondary prevention of metabolic syndrome or onset of its feature might help reduce the risk of death for patients using antipsychotics.

Topics: Adult; Antipsychotic Agents; Clozapine; Diabetes Mellitus, Type 2; Dyslipidemias; Humans; Hypertension; Metabolic Syndrome; Olanzapine; Schizophrenia; Weight Gain

Topics: Antipsychotic Agents; 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

Clozapine, an antipsychotic developed in 1958, is considered the gold standard and the treatment of choice in treatment-resistant schizophrenia despite its side effects and despite 40-70% of these patients not responding to clozapine. In the last decade, new antipsychotics, such as paliperidone palmitate (PP), have emerged as well as its long acting-injectable (LAI) formulations, available as PP-1-monthly (PP1M) and the newest PP-3-montlhy (PP3M). Despite paliperidone having shown a similar efficacy as others antipsychotics for the treatment of schizophrenia, and that PP3M has been shown to reduce relapses compared to oral formulations, no study has been carried out in treatment-resistant schizophrenia. The aim of our study was to carry out an exploratory evaluation of endocrine and hepatic profiles as well as the concomitant treatments associated to PP3M vs. clozapine, the gold standard, in patients with treatment-resistant schizophrenia. We designed a retrospective study. A total number of 33 patients previously diagnosed as schizophrenics treatment-resistant, who were prescribed clozapine followed by PP1M and PP3M when available, were selected. Demographic data, BMI, hepatic enzymes (glutamic oxaloacetic transaminase, glutamate-pyruvate transaminase and gamma-glutamyl transferase (GGT)], thyroid function (thyroid stimulating hormone), blood platelets and both white and red blood cells as well as the use of concomitant antipsychotics, benzodiazepines and biperiden were compared under treatment with clozapine and PP3M. Antipsychotics and benzodiazepines dosages were compared using by the defined daily dose (DDD) method and haloperidol or diazepam dose equivalents. All statistical analyses were performed using the paired Student t-test for repeated measures. Our data showed that patients under treatment with PP3M showed a significant decrease in BMI (P < 0.01), glucose (P < 0.01), cholesterol (P < 0.05) and triglycerides (P < 0.01) when compared with basal values under treatment with clozapine. Hepatic cholestasis enzyme, GGT, were significantly elevated (P < 0.05) under treatment with clozapine when compared to PP3M. Switching clozapine to PP3M led to a significant lower pharmacological exposure to antipsychotics, by both the DDD (P < 0.05) and haloperidol dose equivalents (P < 0.001) methods without increasing the dose of benzodiazepines while biperiden was more used under PP3M. Finally, antipsychotic monotherapy was higher and less polypharmacy was use

Topics: Antipsychotic Agents; Clozapine; Drug Administration Schedule; Drug Resistance; Drug Substitution; Dyslipidemias; Female; Humans; Hyperglycemia; Male; Middle Aged; Obesity; Paliperidone Palmitate; Retrospective Studies; Schizophrenia; Spain

The aim of this study was to investigate correlation of peripheral blood cell counts with the dyslipidemia induced by olanzapine or clozapine in Chinese schizophrenia patients.. A total of 703 eligible schizophrenia patients were enrolled . The counts of red blood cell (RBC), platelet, white blood cell (WBC) and its subtypes, and serum lipids were determined for all participants before and after 2-4 weeks of olanzapine or clozapine treatment.. The two representative second-generation antipsychotics (SGAs), olanzapine and clozapine, markedly caused dyslipidemia in Chinese schizophrenia patients. The tertiles of total RBC counts were positively associated with the odds of having abnormal triglyceride (p < .01) and high-density lipoprotein cholesterol (HDL-C) levels (.05). The tertiles of platelet counts were also positively associated with the odds of having abnormal total cholesterol (.03), low-density lipoprotein cholesterol (p < .01), HDL-C (.01), and non-HDL-C (p < .01). However, the counts of WBC and its some subtypes were negatively correlated with the risk of dyslipidemia in these patients.. The profile of peripheral blood cells may be an early biomarker for predicting the risk of metabolic disorders and cardiovascular diseases in schizophrenia patients treated with SGAs.

Topics: Adult; Antipsychotic Agents; Blood Cell Count; Clozapine; Dyslipidemias; Female; Humans; Lipids; Male; Olanzapine; Risk; Schizophrenia

Type 2 diabetes (T2D) and raised blood lipids are associated with the use of antipsychotics, not least clozapine.. To describe the prevalence of high blood glucose levels, T2D, and dyslipidemia, in association with the use of clozapine or other antipsychotics in patients with schizophrenia in Iceland.. This study identified 188 patients treated with clozapine and 395 patients never treated with clozapine by searching the electronic health records of Landspitali, the National University Hospital. The comparison group consisted of Icelandic population controls. Data were obtained on blood glucose, HbA1c, and blood lipid levels from these health records.. The prevalence of T2D was 14.3% in the clozapine group, where the mean age was 51.2 years, and 13.7% in the never-on-clozapine group, where the mean age was 58.6 years. Males on clozapine were 2.3-times more likely and females 4.4-times more likely to have developed T2D than controls from an age-adjusted Icelandic cohort, while males on other antipsychotics were 1.5-times more likely and females 2.3-times as likely to have T2D than controls. Only one case of ketoacidosis was identified. Triglyceride levels were significantly higher in both treatment groups compared to controls in the age-adjusted Icelandic cohort.. Clinicians must take active steps to reduce the risk of T2D and raised triglycerides in patients with schizophrenia. Antipsychotics were associated with a greater risk of T2D developing in females compared to males.

Topics: Adult; Antipsychotic Agents; Blood Glucose; Case-Control Studies; Clozapine; Cohort Studies; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Dyslipidemias; Female; Humans; Iceland; Lipids; Male; Middle Aged; Prevalence; Risk; Schizophrenia; Sex Factors

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

To investigate INSIG2's association with obesity, weight change and serum lipid profile during clozapine treatment.. Subjects with schizophrenia (n = 190) were genotyped, identifying seven SNPs. Genetic risk scores (GRSs) were calculated to adiponectin, high-density lipoprotein cholesterol, triglycerides and weight gain.. In the model for weight gain, SNPs rs12151787, rs17047733 and rs10490626 were selected. Explanatory variables were BMI (p = 5.05 × 10. INSIG2 plays a role in weight gain and obesity during clozapine treatment.

Topics: Adiponectin; Adult; Antipsychotic Agents; Cholesterol, HDL; Clozapine; Dyslipidemias; Female; Humans; Intracellular Signaling Peptides and Proteins; Male; Membrane Proteins; Middle Aged; Polymorphism, Single Nucleotide; Schizophrenia; Weight Gain

Clozapine is known to be associated with higher risk of metabolic syndrome, including dyslipidaemia, but the mechanisms of such a relationship are still under debate. The case we reported shows a seemingly dose-dependent effect of clozapine on a patient's lipid profiles with no influence on his blood sugar in a relatively short period of time. A direct effect of clozapine on lipid metabolism, independent of insulin or obesity-related metabolic changes, is suggested. The rapid effect of clozapine on lipid profile allows fine-tuning in dose adjustment while treating refractory schizophrenia complicated with drug-related dyslipidaemia but worrying about psychotic rebound during clozapine discontinuation.

Topics: Antipsychotic Agents; Clozapine; Dose-Response Relationship, Drug; Dyslipidemias; Humans; Male; Middle Aged; Schizophrenia; Time Factors

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

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