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Purpose: Clozapine is the effective therapy for treatment-refractory schizophrenia. However, the use of clozapine is limited by its adverse effects. As propranolol is frequently used for the prevention and treatment of clozapine-induced tachycardia, we performed a meta-analysis to evaluate the effects of propranolol on steady state pharmacokinetics of clozapine in schizophrenic patients. Methods: We included 16 retrospective studies on the effects of propranolol on steady state pharmacokinetics of clozapine in schizophrenic patients, with data from both generic and brand name treatment phases in eight clozapine bioequivalence studies conducted in a single center in China from 2018 to 2022. Review Manager 5.4 was used for meta-analysis of the included studies. Results: The SMDs with 95% CIs of AUC0–12, Cmax,ss, C, and C were calculated to be 0.44 (0.23, 0.64), 0.40 (0.20, 0.61), 0.43 (0.22, 0.63), and 0.44 (0.23, 0.64), respectively. These findings proved that combination with propranolol would increase the systemic exposure of clozapine. T1/2 of clozapine was significantly longer in the presence of propranolol than in the absence of propranolol (SMD = 0.32, 95% CI [0.12, 0.52], p = 0.002). There was no statistically significant difference for T of clozapine in the presence or absence of propranolol (SMD = − 0.05, 95% CI [− 0.25, 0.15], p = 0.63). Conclusion: The combination with propranolol could significantly increase systemic exposure and extended T1/2 of clozapine, and thus need to be considered in prescribing decisions. [ABSTRACT FROM AUTHOR]

Danggui Longhui is a traditional Chinese medicine made from the dried root of Angelica sinensis. It is used in psychiatric patients in China to reduce associated constipation. In a population pharmacokinetic model in olanzapine patients from Beijing Anding Hospital, we demonstrate that dangguilonghui tablets doubled olanzapine clearance, indicating the induction of olanzapine metabolism. Olanzapine metabolism is similar to clozapine metabolism. Two cases of possible clozapine induction using dangguilonghui tablets 4 g/day were identified in Beijing Anding Hospital. Dividing the minimum therapeutic concentration of 350 ng/mL by the concentration-to-dose (C/D) ratio provides the minimum therapeutic dose. Case 1 was a female smoker on clozapine for 415 days. The mean of 6 clozapine C/D ratios associated with smoking provided a minimum therapeutic dose of 267 mg/day. There were 6 steady-state concentrations on the combination of valproic acid and dangguilonghui tablets, which provided a much higher minimum therapeutic dose of 833 mg/day. Four steady-state clozapine C/D ratios based on smoking and valproate after 4 months of carbamazepine 200 mg/day provided a minimum therapeutic dose of 603 mg/day. Case 2 was a female non-smoker on clozapine for 58 days. She had 3 clozapine C/D ratios on dangguilonghui tablets with a mean of 0.30 ng/mL providing a minimum therapeutic dose of 1167 mg/day. Future clinical studies with repeated measures need to replicate the possibility that dangguilonghui tablets are a moderate-to-strong inducer of clozapine metabolism as suggested by these two limited cases. [Display omitted] [ABSTRACT FROM AUTHOR]

Clozapine was first manufactured in China in 1976. Clozapine is currently used not only for treatment-refractory schizophrenia (TRS), but also continues to be used in the treatment of patients with non-TRS and other mental disorders; moreover, low-dose clozapine is also used in sedative-hypnotic therapy and in combination with other drugs. There is need for studies in China using various titrations and assessing their risk for myocarditis and aspiration pneumonia. The Chinese clozapine package insert will also greatly benefit from these changes. [ABSTRACT FROM AUTHOR]

Objective. To systematically assess the safety and efficacy of olanzapine versus clozapine when treating senile dementia and to provide evidence-based medicine basis for its promotion and use. Methods. PubMed, Embase, ScienceDirect, Cochrane Library, China Knowledge Network Database (CNKI), China VIP Database, Wanfang Database, and China Biomedical Literature Database (CBM) online database were searched for randomized controlled trials (RCT) of olanzapine and clozapine when treating senile dementia. The retrieval time limit is from the establishment of the database to the present. The data were extracted independently by two researchers, and the bias risk of each contained literature was analyzed in accordance with the standard of Cochrane Handbook 5.3. RevMan 5.4 statistical software was used to analyze the collected data by meta-analysis. Results. Finally, 6 randomized controlled trial articles were included, with a total of 490 samples. Meta-analysis of clinical efficacy showed that the clinical efficacy was similar and there was no significant difference (P > 0.05). Two articles used Alzheimer's disease pathological behavior rating scale (BEHAVE-AD) to compare the pathological behavior of different stages after treatment. Statistical analysis showed that there was no significant difference between the total score of BEHAVE-AD and the scores of each factor in each week after treatment. The non-treatment adverse reaction scale (TESS) of the study group and the control group was analyzed by meta-analysis. The TESS score of the study group after treatment was significantly lower than that of the control group. The BPRS scores of different stages after treatment were analyzed by meta-analysis, and there was no significant difference in the total score and factor scores of BPRS in each week after treatment. Two clinical trials reported the incidence of neurological symptoms after treatment. Olanzapine and clozapine treatment can effectively reduce the risk of aging. There was no significant difference in the incidence of neurological symptoms in patients with dementia (P > 0.05). According to the analysis of meat products, the incidence of adverse reactions in the study group was significantly lower than that in the control group (P < 0.05). Conclusion. Olanzapine and clozapine have similar efficacy when treating mental and behavioral disorders in patients with senile dementia, in which olanzapine is more effective in improving the symptoms of patients with Alzheimer's disease (AD), with less adverse reactions and high safety, which is worth popularizing in clinical practice. However, more studies and follow-up with higher methodological quality and longer intervention time are needed to further verify. [ABSTRACT FROM AUTHOR]

Objective: This study explores the intricate relationship between clozapine use, cardiovascular disease (CVD) risk, and cognitive function in patients with schizophrenia (SCZ)., Methods: A cohort comprising 765 patients was stratified based on clozapine usage. Data on demographics, clinical characteristics, and glycolipid metabolism were collected. The Framingham Risk Score and vascular age were calculated using gender-specific Cox regression calculators. Cognitive function was assessed with the Repeatable Battery for Assessment of Neuropsychological Status., Results: Among the patients, 34.6 % were clozapine users. Clozapine users exhibited lower systolic blood pressure, high-density lipoprotein cholesterol and total cholesterol (all ps < 0.05). Furthermore, clozapine users exhibited higher PANSS scores, along with lower scores in RBANS scores (all p s  < 0.05). Correlation analysis revealed positive correlation between CVD risk in non-clozapine users and negative symptom scores (r = 0.074, p = 0.043), and negative correlation with positive symptom scores and RBANS scores (r = -0.121, p = 0.001; r = -0.091, p = 0.028). Multivariate stepwise regression analysis indicated that attention scores as predictive factors for increased CVD risk in clozapine users (B = -0.08, 95 %CI = -0.11 to -0.03, p = 0.003)., Conclusions: Patients with SCZ using clozapine exhibit more severe clinical symptoms and cognitive impairments. Attention emerges as a predictor for increased CVD risk in clozapine users., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Clozapine is an off-label drug used in most countries to prevent suicide in individuals with schizophrenia. However, few studies have reported real-world prescription practices. This study aimed to explore the association between a history of suicidal behavior and clozapine prescribing during eight weeks of hospitalization for individuals with early-stage schizophrenia., Methods: This observational cohort study used routine health data collected from a mental health hospital in Beijing, China. The study included 1057 inpatients who had schizophrenia onset within 3 years. History of suicidal behavior was coded from reviewing medical notes according to the Columbia Suicide Severity Rating Scale. Information on antipsychotic use during hospitalization was extracted from the prescription records. Time to clozapine use was analyzed using Cox regression models adjusted for sociodemographic and clinical covariates., Results: The prevalence rates of self-harm, suicidal behavior, and suicide attempt were 12.3%, 7.5%, and 5.4%, respectively. A history of self-harm history was positively associated with clozapine uses upon admission (4.1% vs. 0.8%, exact p = 0.009). Among those who had not used clozapine and had no clozapine contraindication, A history of suicidal behavior increased the possibility of switch to clozapine within 56 days after admission (Hazard Ratio[95% CI], 6.09[2.08-17.83]) or during hospitalization (4.18[1.62-10.78])., Conclusion: The use of clozapine for early-stage schizophrenia was more frequent among those with suicidal behavior than among those without suicidal behavior in China, although the drug instructions do not label its use for suicide risk., (© 2024. The Author(s).)

Aim: This study describes antipsychotic prescription patterns for drug‐naïve inpatients diagnosed with first‐episode schizophrenia‐spectrum (FES) disorders and factors associated with practices deviating from China's current guidelines. Methods: All inpatients aged 7 to 45 years experiencing a first episode of schizophrenia‐spectrum disorder with a duration of untreated illness of less than 18 months and admitted between 1 August 2016 and 1 August 2017 to one of eight psychiatric hospitals in Hunan were included. Demographics, clinical characteristics and prescriptions at discharge were collected from electronic medical records. Logistic regression and random forest methods were used to model relationships between demographic and clinical factors and deviations from China's guidelines. Results: Of the 602 inpatients included in the study, 598 (99.3%) were prescribed antipsychotics, and no patients were discharged on long‐acting injectable antipsychotics. Polypharmacy (more than one antipsychotic prescribed) was present in 121 (20.2%) participants. Clozapine was prescribed to 45 (7.5%) patients. Adults receiving polypharmacy were more likely to be prescribed high‐dose antipsychotics than those receiving a single antipsychotic. Minors under 13 years of age were more likely to receive polypharmacy and unapproved antipsychotics than those older than 13 years. Conclusions: Our findings suggest that most of the inpatients were prescribed a single antipsychotic at discharge, consistent with China's guidelines. Minors with FES and patients discharged on polypharmacy and clozapine may require more intense monitoring and management. With the current implementation of China's National Mental Health Working Plan, these results will assist decision‐makers in allocating resources and conducting reforms to facilitate best practice treatment for FES. [ABSTRACT FROM AUTHOR]

aim of the present study was to investigate the point prevalence of and patterns and factors associated with clozapine use in patients with early-stage schizophrenia discharged from a psychiatric hospital in China. Methods: A retrospective study was conducted to analyze the prescriptions of 867 consecutive patients with early-stage schizophrenia who were admitted to the Affiliated Brain Hospital of Guangzhou Medical University between Jan 1, 2011 and Dec 31, 2016. Results: At discharge from the hospital, 114 (13.1%) patients were prescribed clozapine. Among the patients taking clozapine, 93 patients (81.6%) were prescribed clozapine polypharmacy, and only 21 patients (18.4%) were prescribed clozapine monotherapy. None of the patients were prescribed an overdose of clozapine. The mean daily dosage of clozapine was 160.97 mg, 149.05 mg and 213.69 mg among all patients taking clozapine, patients taking clozapine polypharmacy and patients taking clozapine monotherapy, respectively. The antipsychotic most frequently combined with clozapine was risperidone. Logistic regression suggested that the length of hospital stay, high school education, lower benzodiazepine use and antipsychotic polypharmacy were independently and significantly associated with clozapine use (P< 0.05). Conclusion: Although clozapine has been commonly used in China in recent years, the present study found that clozapine was not commonly used in patients with early-stage schizophrenia. An underutilization and delayed initiation of clozapine may exist in a portion of patients with early-stage schizophrenia. Given the unfavorable outcomes of underutilized and delayed clozapine use, future studies may be needed to assess and increase clozapine use in this population. [ABSTRACT FROM AUTHOR]

Few studies have examined clozapine in cohort studies of Chinese patients with schizophrenia in rural primary care. The objective of this two-year cohort study was to describe the usage of clozapine and investigate and identify the demographic, clinical correlations and risk variables which affect the use of clozapine in patients with schizophrenia. A random cluster sampling technique was used, and participants were collected from the China National Psychiatric Management System (CNPMS). The variables for clozapine use in individuals with schizophrenia who had undergone a two-year follow-up were determined using the generalised estimating equation (GEE). In this study, 742 patients with schizophrenia were invited, and 491 completed the two-year follow-up study. Being married, having more years of education, having more waist circumference, using mood stabilisers, using anticholinergic, and having higher ITAQ (Insight and Treatment Attitude Questionnaire) scores were more significantly related to using clozapine. Older age of onset, using second-generation antipsychotics (SGAs) except clozapine, predicted a lower prevalence of using clozapine. The usage of clozapine was very common in patients with schizophrenia treated by primary care physicians and was influenced by a variety of factors, including the price of drugs, clinical factors, health regulations, and the characteristics of the treatment environment. Further examination of the rationale and appropriateness of clozapine in primary care in China is necessary. [ABSTRACT FROM AUTHOR]

Objective Serious infections or inflammations have been associated with serum clozapine concentration increases and sometimes with clozapine toxicity. Method These two cases describe Chinese patients (Case 1: a 57-year-old female nonsmoker with severe dermatitis and Case 2: a 47-year-old male nonsmoker with influenza and secondary infection). Results In both cases, the Drug Interaction Probability Scale established the presence of a probable drug–drug interaction. In both cases, the clozapine and the total clozapine concentration-to-dose ratios followed a temporal pattern (normal–high–normal), consistent with an inhibition of clozapine metabolism during peak inflammation. In the first case, the total clozapine concentration-to-dose ratio (8 with no/low inflammation: median of 3.10 and 2 at peak inflammation: median of 3.90) provided a significant difference (P = 0.044). In the second patient, because of the smaller sample size and reduced statistical power (4 with no infection: a median of 1.59 and 2 at peak infection: 3.46), the increase did not reach significance (P = 0.13). In the first case, the median baseline clozapine concentration-to-dose ratio increased by a factor of 1.45 from 2.00 to a peak of 2.89. To compensate for the inhibition of clozapine metabolism, the dose correction factor was 0.69 (1/1.45) or a decrease in dose of approximately one-third. In the second case, the median baseline clozapine concentration-to-dose ratio increased by a factor of 2.56 from 1.15 to a peak of 2.94. Conclusion This provided a dose correction factor of 0.40 (1/2.56) or approximately half the dose, similar to published cases in Caucasians with serious respiratory infections. [ABSTRACT FROM AUTHOR]

Objective: Clozapine is one of the most commonly used antipsychotic drugs in China, To date, few studies have investigated the patterns the prescription of clozapine nationwide. The present study examined these patterns in China in 2006 and identified the demographic and clinical characteristics associated with the use of clozapine. Methods: Using a standardized protocol and data collection procedure, we surveyed 5,898 patients with schizophrenia in 10 provinces with differing levels of economic development. Results: Overall, clozapine had been prescribed for 31.9% (n=1,883) of the patients; however we found considerable variation among the 10 provinces. The frequency of clozapine use was highest in Sichuan (39.3%) and lowest in Beijing (17.3%). The mean daily dose of clozapine was 210.36±128.72 mg/day, and 25.1% of the patients were treated with clozapine in combination with other antipsychotics. Compared with the group not receiving clozapine, clozapine-user had been treated for longer durations and had experienced a greater number of relapses and hospitalizations. Furthermore, those in the clozapine-user had lower family incomes, were less able to seek psychiatric services, and more likely to be male and have a positive family history of schizophrenia. A multiple logistic regression analysis revealed that age, sex, professional help-seeking behaviors, duration of illness, economic status, educational level, and clinical manifestations were associated with the use of clozapine. Conclusion: Clozapine use is common in China. However, use of the antipsychotic varies among provinces, and demographic and clinical factors play important roles in the prescription of clozapine. [ABSTRACT FROM AUTHOR]

Objective: Optimizing treatment and outcomes for people with schizophrenia requires understanding of how evidence-based treatments are utilized. Clozapine is the most effective antipsychotic drug for treatment-refractory schizophrenia, but few studies have investigated trends and patterns of its use over time internationally. This study examined the prescription patterns of clozapine and its demographic and clinical correlates in Asia from 2001 to 2009. Method: Clozapine prescriptions were collected in a sample of 6761 hospitalized schizophrenia patients in nine Asian countries and regions using a standardized protocol and data collection procedure. Results: Overall, the proportion of patients receiving clozapine prescriptions was stable across the three surveys from 2001 to 2009, ranging from 14.5% to 15.9%. However, the rates and patterns observed within different regions and countries at each survey differed considerably. Clozapine use decreased significantly over time in China, while it increased in Korea and Singapore. Multiple logistic regression analysis revealed that patients taking clozapine were significantly younger, had a higher dose of antipsychotic drugs in chlorpromazine equivalents, were more likely to be female, had fewer extrapyramidal symptoms, and had more negative symptoms, admissions and weight gain in the past month than those not receiving clozapine. Conclusion: The variability in overall rates and changes in prescription rates over time in these samples suggest that factors other than psychopharmacological principles play an important role in determining the use of clozapine in schizophrenia in Asia. [ABSTRACT FROM AUTHOR]

Objective: To determine the incidence, characteristics, and predictors of clozapine-induced fever in a sample of patients in a local psychiatric unit. Method: A retrospective review of case notes of 227 inpatients newly started on clozapine from March 2003 to December 2006 was conducted. Demographic characteristics, presence of fever, investigations carried out, fever characteristics, and complications of fever were recorded and analyzed. Patients with clozapine-induced fever were compared with their fever-free counterparts on demographic and clinical factors. Multivariate logistic regression was performed to identify predictors of clozapine-induced fever. Results: Thirty-one out of 227 patients (13.7%) developed clozapine-induced fever. The means for day of onset of clozapine-induced fever after clozapine initiation and duration of fever were 13.7 and 4.7 days, respectively. The mean highest body temperature was 38.8 °C. Fever resolved within 48 hours after clozapine discontinuation in 79% of the patients with clozapine-induced fever. One out of 7 patients (14.3%) had fever on re-challenge. Clozapine-induced fever was associated with rate of titration more than 50 mg/wk (OR 18.9; 95% CI 5.3 to 66.7; P < 0.01), concomitant use of valproate (OR 3.6; 95% CI 1.5 to 8.9; P = 0.01), and presence of physical illnesses (OR 3.2; 95% CI 1.2 to 8.3; P = 0.02). Conclusion: Clozapine-induced fever is common. Temporary withdrawal of clozapine may result in resolution of fever, and clozapine re-challenge may be considered after fever subsides. Slower rate of clozapine titration may be helpful in patients with underlying physical illness and concomitant valproate treatment. [ABSTRACT FROM AUTHOR]

What is already known about this subject • Plasma concentrations of clozapine (CLZ) and its active metabolite vary considerably at a given dosage. • A number of patient-related factors have been reported to increase the variability of plasma CLZ concentrations, with gender, age and smoking behaviour representing some of the more important contributing variables • However, results of previous studies concerning these factors have been inconsistent and most studies were conducted in western populations. What this study adds • Using this ethnically unique, relatively large sample, we replicated some findings in western populations, including large interindividual variability of plasma CLZ concentrations, significant effects of gender on plasma CLZ concentrations. • Female patients had significantly higher levels than males and no significant differences in plasma CLZ concentrations were observed between male smokers and nonsmokers, despite the CLZ dosage for smokers being significantly higher. Aim To study the relationship between age, gender, cigarette smoking and plasma concentrations of clozapine (CLZ) and its metabolite, norclozapine (NCLZ) in Chinese patients with schizophrenia. Methods Data from a therapeutic drug monitoring programme were analysed retrospectively. One hundred and ninety-three Chinese inpatients with schizophrenia were assessed using clinical data forms. Steady-state plasma concentrations of CLZ and NCLZ were assayed using high-performance liquid chromatography. Comparisons of dosage and plasma CLZ concentrations were undertaken between males ( n = 116) and females ( n = 77), younger (≤40 years, n = 82) and older patients (>40 years, n = 111) and current male smokers ( n = 50) and nonsmokers ( n = 66). Results (i) Plasma CLZ concentrations demonstrated large interindividual variability, up to eightfold at a given dose; (ii) there were significant effects of gender on plasma CLZ concentrations (relative to dose per kg of body weight) with female patients having significantly higher concentrations than males (30.09 ± 24.86 vs. 19.87 ± 3.55 ng ml−1 mg−1 day−1 kg−1; P < 0.001); (iii) there were no significant differences in plasma CLZ concentrations between those patients ≤40 years old and those >40 years; and (iv) there were no significant differences in plasma CLZ concentrations between male smokers and nonsmokers, despite the CLZ dosage for smokers being significantly higher. Conclusions Plasma CLZ concentrations vary up to eightfold in Chinese patients. Among the patient-related factors investigated, only gender was significant in affecting CLZ concentrations in Chinese patients with schizophrenia, with female patients having higher levels. [ABSTRACT FROM AUTHOR]

Objective. To determine current patterns of antipsychotic medication use and metabolic complications among hospitalized Chinese patients with schizophrenia. Method. A total of 503 inpatients who met ICD-10 diagnostic criteria for schizophrenia were enrolled. Demographic features and records of current treatment (medication, dose, duration of treatment) were collected through cross-sectional chart review along with biophysical parameters (body mass index and laboratory findings). Results. (1) Most patients (457/503, 90.9%) were found to receive antipsychotic monotherapy; (2) clozapine was the most common medication used (152/507, 30.2%); (3) the subset of patients treated within the course of a first episode psychosis, or with less than 5 years of illness, were more likely to be treated with second-generation antipsychotics (SGAs) than with conventional antipsychotic medications or clozapine; (4) patients treated with clozapine or conventional antipsychotics were more likely to manifest metabolism-related physical conditions than those receiving SGAs. Conclusion. Conventional antipsychotics and clozapine constitute the current mainstream of schizophrenia treatment in China where a lower percentage of patients receive SGAs other than clozapine than in developed countries. The high incidence of treatment-related metabolic complications in this population suggests that these issues are under-appreciated based on current patterns of medication use. [ABSTRACT FROM AUTHOR]

Aims Few studies have investigated the prescription patterns of clozapine in outpatients with schizophrenia in China. It is an important issue due to clozapine's high efficacy and potentially fatal side effect profile. This study examined the use of clozapine and its correlates in China. Methods Three hundred ninety-eight clinically stable outpatients with schizophrenia were randomly selected and interviewed in Hong Kong (HK) and Beijing (BJ). Assessment instruments included the Structured Clinical Interview for DSM-IV, Brief Psychiatric Rating Scale, Simpson and Angus Scale of Extrapyramidal Symptoms, Barnes Akathisia Rating Scale and the Hong Kong and Mainland China World Health Organization Quality of Life Schedule-Brief version. Assessments were performed by the same investigator in both sites. Results Clozapine was prescribed to 15.6% of (n = 62) patients. There was a wide inter-site variation between HK and BJ. Use of clozapine was associated with age, age at onset, extrapyramidal side effects (EPS), having health insurance, use of depot and typical antipsychotic and anticholinergic drugs and benzodiazepines as well as history of suicidal attempts. On multiple logistic regression analysis, the number of hospitalizations, site (HK vs. BJ), use of typical antipsychotics, polypharmacy and co-prescription with anticholinergics were significantly associated with the prescription of clozapine. No significant differences were found between the clozapine and non-clozapine groups with regard to any of the quality of life domains. Conclusion A combination of economical and clinical factors, health policies and the characteristics of the treatment settings plays important roles in determining clozapine use. Clozapine appears to have little significant influence on quality of life in clinical stable Chinese patients with schizophrenia. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article presents author's comments on the clozapine induced myocarditis with the incidence in clozapine patients. It mentions that clozapine is widely prescribed by majority of medical personnel in China. It mentions that clozapine was a first antipsychotic drug prescribed in the patients with severe mood disorders.

Clozapine (CLZ) is a neuroactive pharmaceutical that is frequently detected in aquatic environments. Although the cardiotoxicity, developmental toxicity, and neurotoxicity of CLZ in aquatic non-target organisms have been reported, its lipotoxicity and underlying mechanism are unknown. Therefore, in this study, 2-month-old Chinese rare minnows were exposed to 0, 0.1, 1, and 10 μg/L CLZ for 90 days. Overt dyslipidemia was observed after CLZ exposure, whereas the body weights of females significantly increased after CLZ exposure (p < 0.05). In addition, obvious hepatocyte vacuolization and hepatic lipid droplet accumulation were observed at all treatment groups (p < 0.05). The activities of sterol regulatory element binding proteins 1 (SREBP1) and fatty acid synthase (FAS) were significantly upregulated at the 1 and 10 μg/L CLZ treatment groups (p < 0.05). Moreover, evident cell boundary disintegration of the intestinal villi and increasing mucus secretion were observed at all treatment groups (p < 0.05). Furthermore, the diversity of the gut microbiota increased, whereas the relative abundances of Proteobacteria, Firmicutes and Bacteroidetes significantly increased after CLZ exposure (p < 0.05). Furthermore, significantly increased bacterial secondary bile acid biosynthesis activity in Chinese rare minnows was observed after 1 μg/L CLZ exposure (p < 0.05). Therefore, our findings confirmed that CLZ induced lipotoxicity by stimulating SREBP1 and affecting the bacterial secondary bile acid biosynthesis activity in Chinese rare minnows., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: To investigate the patterns and correlates of antipsychotic prescriptions among recently discharged inpatients with schizophrenia in China., Methods: The study included discharged patients from 41 tertiary psychiatric hospitals in 29 provinces between March 19-30, 2019. A total of 1032 inpatients with schizophrenia were included. Socio-demographic and clinical data were retrieved from medical records upon discharge., Results: Patients received a total of 13 unique antipsychotic medications, which included 9 s-generation antipsychotics (SGAs) and 4 first-generation antipsychotics (FGAs). The utilization rates of SGAs and FGAs were 98.8 % and 6.1 % respectively. The three most commonly antipsychotic medications were risperidone (35.1 %), olanzapine (31.3 %), and clozapine (24.6 %). The mean chlorpromazine equivalent dose was 452.12 ± 230.74 mg/day. The utilization rate of mood stabilizers was 18.9 %, 8.8 % for antidepressants, 20.3 % for sleep improvers, and 9.9 % for anticholinergics. More than two fifths patients (43.1 %) received two or more antipsychotic medications. Predictors of antipsychotic polypharmacy included younger age, residing in Central or West China, a longer duration of illness, a history of prior hospitalizations, and having agitated behavior during the hospitalization., Conclusion: Antipsychotic polypharmacy in China is common on inpatients settings. The proportion of antipsychotic polypharmacy in China is higher than in many other countries, despite limited data to support the efficacy of many combinations. Clozapine remains one of most commonly prescribed antipsychotics in China, either as a monotherapy or combination therapy., (Copyright © 2021. Published by Elsevier B.V.)

Background: Olanzapine and clozapine are atypical antipsychotics (AAPs) with the greatest risk of weight gain, and changes in feeding behavior are among the most important underlying mechanisms. However, few studies have investigated the role of diet-alone interventions in improving individuals' weight gain by taking AAPs. In closed management mental hospitals of China, family members are allowed to bring food to patients regularly, causing patients to have caloric intake added to their 3 daily meals. However, during the global pandemic of coronavirus disease 2019 (COVID-19), bringing food to the hospital was temporarily prohibited in mental health institutions in China to prevent the spread of the virus. This study sought to compare the body weight and body mass index (BMI) changes of patients taking olanzapine or clozapine undergoing diet-alone interventions caused by this prohibition., Methods: A retrospective self-controlled study was conducted on 90 patients with schizophrenia from a single-center treated with olanzapine or clozapine monotherapy, or combined with aripiprazole or ziprasidone which has a small metabolic impact. A paired-samples t-test was used to compare the changes in body weight and BMI before and after the 3-month prohibition, and general linear regression was used to analyze the effects of gender, age, disease course, duration of drug exposure, and equivalent dose on the BMI improvement. Also, the percentage of people who lost weight and that of individuals who lost 5% of their pre-prohibition body weight were calculated., Results: Paired-samples t-test showed that after 3-month prohibition, the patients' body weight (71.68±6.83 vs. 66.91±7.03, P<0.001) and BMI (26.43±2.11 vs. 24.63±1.81, P<0.001) decreased significantly. Weight loss rate accounted for 99.1%, and weight loss of 5% from the pre-prohibition body weight accounted for 71.8%. General linear regression showed that the duration of drug exposure (β =-0.678, P<0.001) was significantly and negatively correlated with the BMI changes. No significant correlation of gender, age, disease course, or equivalent dose with BMI changes was found., Conclusions: Diet-alone interventions facilitate weight loss in chronically hospitalized schizophrenia patients taking AAPs. Conduction of dietary intervention in the early stages of medication may yield greater benefits.

A letter to the editor is presented about the difficulty of persuading Chinese patients in Singapore to go on a trial of clozapine.

Objective: We examined the time trends and correlates of clozapine use in schizophrenia patients in China., Method: A total of 14,013 patients with schizophrenia treated in 45 psychiatric hospitals/centers nationwide were interviewed in 2002, 2006 and 2012. Patients' socio-demographic and clinical characteristics including psychopathology, medication side effects, satisfaction with treatment and quality of life (QOL) were recorded in a standardized fashion., Results: Clozapine was used in 32.9% of the whole sample; with corresponding figures of 39.7%, 32.5% and 26.4% in 2002, 2006 and 2012 (p<0.001). Families of clozapine users had lower satisfaction with treatment than those of the non-clozapine group, without significant differences with respect to patients' treatment satisfaction and mental or physical QOL. In multiple logistic regression analyses, compared to the non-clozapine group, patients on clozapine had an earlier age of onset, longer illness duration, more global illness severity and drug-induced central nervous system, gastrointestinal and other side effects, lower antipsychotic doses, less delusions and hallucinations, more negative symptoms, were more likely male, inpatients, to have a family history of psychiatric disorders, receive treatments in regional centers and receive antipsychotic polypharmacy, but less likely to have health insurance and receive first-generation antipsychotics and benzodiazepines (R(2)=0.498, p<0.001)., Conclusions: Clozapine was used in one-third of schizophrenia patients in China, with decreasing frequency since 2002. Patients prescribed clozapine had multiple markers of greater global illness severity/chronicity and decreased satisfaction with treatment by the families, but similar QOL and less delusions and hallucinations than patients not prescribed clozapine., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: The treatment of schizophrenia with multiple antipsychotic drugs is common, but the benefits and risks are not known. Methods: In a randomized, double-blind study, we evaluated patients with schizophrenia and a poor response to treatment with clozapine. The patients continued to take clozapine and were randomly assigned to receive eight weeks of daily augmentation with 3 mg of risperidone or with placebo. This course of treatment was followed by an optional 18 weeks of augmentation with risperidone. The primary outcome was reduction in the total score for severity of symptoms on the Positive and Negative Syndrome Scale (PANSS). The secondary outcomes included cognitive functioning. Results: A total of 68 patients were randomly assigned to treatment. In the double-blind phase, the mean total score for the severity of symptoms decreased from baseline to eight weeks in both the risperidone and the placebo groups. There was no statistically significant difference in symptomatic benefit between augmentation with risperidone and placebo: 9 of 34 patients receiving placebo and 6 of 34 receiving risperidone responded to treatment (P=0.38). The mean difference in the change in PANSS scores from baseline to eight weeks between those receiving risperidone and those receiving placebo was 0.1 (95 percent confidence interval, −7.3 to 7.0). The verbal working-memory index showed a small decline in the risperidone group and a small improvement in the placebo group (P=0.02 for the comparison between the two groups in the change from baseline). The increase in fasting blood glucose levels was mildly greater in the risperidone group than in the placebo group (16.2 vs. 1.8 mg per deciliter [0.90 vs. 0.10 mmol per liter], P=0.04). The incidence and severity of other side effects did not differ between the two groups. Conclusions: In this short-term study, the addition of risperidone to clozapine did not improve symptoms in patients with severe schizophrenia. (ClinicalTrials.gov number, NCT00272584) N Engl J Med 2006;354:472-82. [ABSTRACT FROM AUTHOR]

Examines the influence of clozapine on the occurrence of an obsessive-compulsive (OC) symptoms among schizophrenic patients in Hong Kong. Association of psychosocial functions decline with somatic hallucination; Effectiveness serotonin reuptake inhibitors in abating clozapine-induced OC symptoms; Clinical administration of clozapine to the patient.