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Objective: To determine the occurrence of constipation in local patients on clozapine treatment, and to compare the demographical and clinical characteristics of patients on clozapine treatment with or without constipation. Methods: This is a cross‐sectional, observational study. All adult psychiatric out‐patients on clozapine treatment attending follow‐up at a regional hospital were recruited for clinical interview and medical record review. The Enhanced Asian Rome III Questionnaire (EAR3Q) was used to define patients with constipation. The Bristol Stool Form Scale (BSFS) was used to assess stool form. The Brief Psychiatric Rating Scale‐Anchored (BPRS‐A) was used to measure psychiatric symptoms. The Brief Medication Adherence Scale (BMAS) was used to assess treatment adherence. Logistic regression was conducted to identify independent associating factors of constipation in patients on clozapine treatment. Results: The prevalence of constipation in patients on clozapine treatment was 26.3%, (95% CI [21.5%, 31.6%]). Independent associating factors included disorder of psychological development (aOR = 6.98, 95% CI [1.24, 39.18]), anxiety (very mild: aOR = 9.23, 95% CI [2.59, 32.87]; mild: aOR = 2.66, 95% CI [1.26, 5.62]), prescription with combination of laxatives (aOR = 0.40, 95% CI [0.17, 0.95]), and concomitant use of amisulpride (aOR = 2.52, 95% CI [1.09, 5.82]), quetiapine (aOR = 5.92, 95% CI [1.11, 31.56]) and metamucil (aOR = 9.30, 95% CI [1.53, 56.58]). Conclusion: This study examined the prevalence of clozapine‐associated constipation in Hong Kong using a validated questionnaire. The identification of independent factors associated with constipation could facilitate better risk stratification and risk modification in clinical practice. [ABSTRACT FROM AUTHOR]

Objective: This study surveyed clinicians in psychiatry in Hong Kong and Singapore to understand their familiarity and prescribing practices in treatment-resistant schizophrenia (TRS) and clozapine-resistant schizophrenia (CRS). Materials and methods: All clinicians in psychiatry in both regions were invited through email to participate in an anonymous online survey. The survey collected information on the participants' characteristics, their familiarity and experience with clozapine use, and their treatment practices in TRS and CRS. Data collection took place between September 2019 and February 2020 in Hong Kong and December 2018 and March 2019 in Singapore. Results: 261 clinicians responded to the survey, with response rates of 19% (105 out of 556 participants) in Hong Kong and 50% (156 out of 309 participants) in Singapore. The majority of respondents (99.0% in Hong Kong; 87.9% in Singapore) were familiar with treatment guidelines for TRS. However, approximately half (54.2% in Hong Kong; 41.7% in Singapore) delayed the prescription of clozapine when indicated. In terms of alternatives to clozapine, approximately half or more of the clinicians in both regions would use high dose antipsychotics, long-acting injectable antipsychotics, antipsychotic polypharmacy, while the adjuvant use of mood stabilizers and electroconvulsive therapy differed between the two regions. In those with CRS, between 10 and 20% of the respondents added adjuvant mood stabilizers or antipsychotics, and 3-10% would use an antidepressant. Conclusion: Clozapine delays occur in spite of clinicians' familiarity with treatment guidelines. More research is needed to guide the use of augmentation strategies and the search for effective treatments beyond clozapine. [ABSTRACT FROM AUTHOR]

Metabolic syndrome is one of the most common side effects of antipsychotic treatment in patients with schizophrenia. However, previous research has mainly focused on the efficacy of antipsychotic drug treatment, and there are few neuroimaging studies on its side effects on metabolic syndrome in patients with schizophrenia. The purpose of this study was to investigate the characteristics of brain function in schizophrenic patients with metabolic syndrome treated with risperidone or clozapine. 43 schizophrenia patients treated with risperidone or clozapine were included and divided into schizophrenia metabolic syndrome group (SCZ-MetS, n=20) and schizophrenia non-metabolic syndrome group (SCZ-nMetS, n=23), and 28 normal controls (HC, n=28) were collected. All subjects underwent resting-state MRI scans and regional homogeneity (ReHo) was applied to assess brain activity. Analysis of variance (ANOVA) was used to obtain the brain areas with significant differences among the three groups, and then post hoc tests were calculated for comparison between groups. Compared with HC group, the ReHo of right postcentral gyrus, left superior parietal gyrus and left middle occipital gyrus decreased in both groups. In SCZ-MetS, the left calcarine fissure and surrounding cortex and the right angular gyrus decreased, while in SCZ-nMetS, the ReHo in the left superior occipital gyrus and right precuneus decreased, and the right orbital inferior frontal gyrus increased. The ReHo of the right orbital inferior frontal gyrus of SCZ-MetS was lower than that of SCZ-nMetS. There was a significant negative correlation between ReHo and BMI in the right orbital inferior frontal gyrus of schizophrenic patients(r=-0.448, p=0.003). The intrinsic brain dysfunction of orbitofrontal lobe may be related to metabolic syndrome in patient treated with risperidone or clozapine. This finding provides a target for the development of antipsychotics with low side effects. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) is one of the common side effects after antipsychotic treatment of psychosis, but its potential neural mechanism is still unclear. The purpose of this study was to explore the topological characteristics of white matter networks in schizophrenia patients with metabolic syndrome (SCZ-MetS) treated with risperidone and clozapine by graph theory. We obtained diffusion tensor imaging (DTI) data from 39 schizophrenia patients treated with risperidone and clozapine (including 19 patients with metabolic syndrome (SCZ-MetS) and 20 patients without metabolic syndrome (SCZ-nMetS)) and 25 healthy controls (HC). Network topology attributes were calculated using DTI-based graph theory analysis and ANCOVA was used to compare the differences of network topology attributes among the three groups. Correlation between brain regions and clinical metabolic indexes and scale scores The white matter networks of the three groups showed obvious small-world properties. Compared with the HC, bilateral thalamic nodal degree (DC) and nodal efficiency (NE) were decreased in both groups. In the SCZ-MetS, the global efficiency (Eg) and characteristic path length (Lp) were decreased, and the DC and NE of brain regions such as supra-occipital and angular gyrus decreased. Compared with SCZ-nMetS, SCZ-MetS had lower Eg, Lp, and NE in the left medial frontal gyrus and left gyrus rectus. The Eg and Lp, NE of significantly different brain regions were negatively correlated with BMI, waist, and hip circumference in the two groups. There are differences in the topological properties of the brain white matter network between schizophrenia with metabolic syndrome and those without metabolic syndrome after treatment with risperidone and clozapine, which may provide new insights into the brain mechanism behind metabolic syndrome after treatment in psychotic patients. [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]

• Clozapine is an effective antipsychotic medication for treatment resistant schizophrenia and is widely used in some Asian countries. • Regular surveys are useful to rationalize the prescription patterns of psychotropic medications in clinical settings. • In total, 18.4% of schizophrenia patients received clozapine in Asian patients with schizophrenia, from 2.6% in Japan to 32.3% in Hong Kong. • The clinical rationale of clozapine prescription needs careful consideration in Asia. Clozapine is an effective antipsychotic medication for treatment resistant schizophrenia and is widely used in Asian countries. This study investigated clozapine prescription patterns and their associated factors in Asian countries and territories based on the database of the Research on Asian Psychotropic prescription study (REAP) conducted in 2016. Demographic and clinical information of 3744 schizophrenia patients in 15 Asian countries and territories was collected with a standardized data collection form. In total, 18.4% of the sample received clozapine, ranging from 2.6% in Japan to 32.3% in Hong Kong. Binary logistic regression analysis revealed that higher antipsychotic dose (OR = 1.002, P < 0.001), less frequent first admission in the sample (OR = 0.6, P < 0.001), more severe negative symptoms (OR = 1.4, P = 0.001) and less first generation antipsychotics (FGAs) (OR = 0.2, P < 0.001) were independently and significantly associated with clozapine prescription. Clozapine is frequently and increasingly prescribed for schizophrenia in Asia, with large variation across countries and territories. Given the diverse prescription patterns of clozapine found in Asian countries/territories, the clinical rationale of clozapine prescription needs careful consideration in Asia with more local input. [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.