Clozapine Prescribing Research Articles

Psychiatrists' views on clozapine prescribing in Ireland.

Despite proven effectiveness in refractory schizophrenia, clozapine remains underutilised, and it is important to understand potential reasons for this. This study's aim was to examine in a National sample of Consultant Psychiatrists their knowledge of, attitudes and perceived barriers to clozapine use. A novel questionnaire was designed and distributed by email to 275 Consultant Psychiatrists in Republic of Ireland. Twenty-eight percent (n = 77) completed the survey, with 55% of respondents practicing for 15 or more years. Clinicians expressed confidence in managing clozapine treatment and side effects and were well aware of clozapine's clinical effectiveness and guideline-based use. A majority indicated insufficient experience managing rechallenge and half expressed insufficient experience managing adverse events. Perceived patient factors were highlighted as barriers with 69% of respondents reporting patients' concern about effectiveness and 50% regarding tolerability. Sixty-four percent (n = 40) indicated that a specialised/tertiary clozapine service would facilitate initiation, with 57% (n = 36) reporting less frequent blood monitoring would aid clozapine prescribing. A majority identified that access to dedicated staff (81%, n = 51) and dedicated day hospital services (84%, n = 53) would facilitate community initiation. Consultants are familiar with clozapine use and related guidelines. Dedicated staff and facilities for clozapine use is one identified structural change to enhance clozapine prescribing in Ireland. Tertiary service or clinical advice service would assist in clozapine rechallenge cases or in managing significant adverse events. More structured patient education regarding clozapine effectiveness and professional development programmes focused on managing side effects and rechallenge may promote clozapine use.

Survey on barriers to psychiatrists' use of clozapine for young people in Scotland and suggestions for reducing these.

The Mental Welfare Commission for Scotland published a report into the death of a young person, with recommendations for the Royal College of Psychiatry in Scotland Child and Adolescent Faculty; to explore if there were barriers to the use of Clozapine in young people in Scotland. A mixed-methods study was performed using a cross-sectional survey of clinicians working in child and adolescent psychiatry across Scotland, to determine attitudes towards clozapine use and the perceived barriers and facilitators to clozapine treatment. Results suggest that there may be a lack of clearly defined pathways within and between services, as well as a lack of resources provided for the necessary monitoring of a young person started on clozapine. Multiple respondents felt unskilled in clozapine initiation and had not accessed formal training. The most frequently mentioned themes for improving facilitation of clozapine prescription were that of increased resources and training. National policymakers including the Mental Welfare Commission, NHS Education for Scotland, and NHS Scotland should consider these findings to address the potential underutilisation of clozapine for people aged under 18 in services across Scotland. A review of current service provision should take place, with consideration of whether the facilitators to clozapine prescription which our study has highlighted could be implemented more effectively. This may help reduce identified barriers and increase clozapine prescription to those who would benefit from it, potentially improving outcomes for young people with treatment-resistant psychosis.

History of suicidal behavior and clozapine prescribing among people with schizophrenia in China: a cohort study

BackgroundClozapine 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.MethodsThis 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.ResultsThe 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]).ConclusionThe 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.

Clozapine Proficiency as a Milestone in Psychiatric Training

This Viewpoint advocates for the addition of clozapine prescribing as a milestone in psychiatric education.

Changes in psychopharmacotherapy for patients with schizophrenia in a psychiatric institution in Japan: A 12-year prescription survey pre- and post-introduction of clozapine

Psychopharmacotherapy for patients with schizophrenia in Japan has a long history of polypharmacy, which is rare worldwide but remains a critical problem. One reason for this is that clozapine was not available in Japan until 2009. We aimed to investigate the changes in psychopharmacotherapy in patients with schizophrenia over 12 years pre- and post-introduction of clozapine to clarify how psychopharmacotherapy for patients with schizophrenia has changed with the introduction of clozapine. We retrospectively collected data from the medical records of inpatients diagnosed with schizophrenia at the Okayama Psychiatric Medical Center. Chlorpromazine equivalent (CP-eq) decreased from 1276.6 mg/day in 2009 to 613.9 mg/day in 2020. The prescribed daily dose/defined daily dose (PDD/DDD) decreased from 3.0 in 2009 to 1.2 in 2020. The monotherapy rate increased from 24.4 % in 2009 to 74.6 % in 2020. Our institution began using clozapine in 2010, and the prescription rate for clozapine increased to 37.3 % in 2020. The prescription rate for more than three antipsychotics decreased from 27.8 % in 2009 to 0.8 % in 2020.The increase in clozapine prescription has contributed to an increased rate of antipsychotic monotherapy and a decreased rate of polypharmacy, promoting the optimization of schizophrenia medication. Clozapine therapy should be further promoted in Japan to reduce treatment-resistant schizophrenia due to polypharmacy as much as possible.

Hematological impact of COVID-19 mRNA vaccination in patients treated with Clozapine

IntroductionClozapine is an atypical antipsychotic that is primarily prescribed for treatment-resistant schizophrenia. Despite its proven efficacy, the prescription of clozapine is sometimes limited by its hematologic side effects, including agranulocytosis. During the SARS-CoV-2 pandemic, schizophrenia is recognized as a risk factor for developing severe forms of the infection. Early and complete vaccination of patients has been recommended. However, there is limited data on the effect of the vaccine on the risk of hematologic abnormalities in patients treated with clozapine.ObjectivesTo study the hematologic effect of the mRNA vaccine against COVID-19 in a population of patients with treatment-resistant schizophrenia treated with clozapine.MethodsTwenty-five patients hospitalized for schizophrenia at the forensic psychiatry department of Razi Hospital in Manouba, Tunisia, were included. Eighteen patients were treated with clozapine, and seven patients were treated with other antipsychotics. Consent from patients and/or their relatives was obtained before vaccination. The results of complete blood counts performed as part of the therapeutic protocol were compared between the two groups before and after administration of the vaccine.ResultsNo patient experienced agranulocytosis induced by clozapine after vaccination against COVID-19.Blood cells counts,red blood cells counts,and platelets were within the normal ranges.However,a decrease in the number of WBCs,neutrophils,and lymphocytes was observed in patients treated with clozapine without significant difference compared to the patients treated with other neuroleptics, but there was no severe neutropenia or need to stop treatment.ConclusionsThe prescription of clozapine, the introduction protocol, and treatment administration have been greatly influenced by the COVID-19 pandemic due to the hepatotoxic risk of the drug. Vaccination is essential to prevent severe forms of the infection, especially in at-risk populations such as patients treated for schizophrenia.The potentiation of hematologic side effects induced by clozapine by the vaccine is not documented.The COVID-19 mRNA vaccine is safe even with clozapineDisclosure of InterestNone Declared

Racial Disparities in Clozapine Prescription Patterns Among Patients With Schizophrenia.

Previous research has suggested that demographic factors affect the likelihood of a patient with schizophrenia receiving a clozapine prescription. The authors aimed to determine the impact of race, social determinants of health, gender, rurality, and care patterns on clozapine prescription rates. This cross-sectional observational study used structured electronic health records data from 3,160 adult patients diagnosed as having schizophrenia between October 1, 2015, and November 30, 2021, in a multifacility health system. The social vulnerability index (SVI) was used to quantify social determinants of health. Descriptive data analysis, logistic regression, and sensitivity analysis were conducted to identify differences between patients with schizophrenia who received a clozapine prescription and those who received antipsychotic medications other than clozapine. Overall, 401 patients with schizophrenia were given a clozapine prescription during the study period, and 2,456 received antipsychotics other than clozapine. Results of the logistic regression indicated that White race (OR=1.71, compared with Black race), community minority status and language SVI score (OR=2.97), and increased treatment duration (OR=1.36) were significantly associated with a higher likelihood of clozapine prescription; gender, rurality, age at first diagnosis, and ethnicity did not influence the likelihood of receiving clozapine. Black patients with schizophrenia had a lower likelihood of receiving a clozapine prescription compared with White patients, even after analyses accounted for demographic variables, social determinants of health, and care access patterns. Given the effectiveness of clozapine in managing treatment-resistant schizophrenia, it is crucial for future research to better understand the factors contributing to this treatment disparity.

Variation of Clozapine Use for Treatment of Schizophrenia: Evidence from Pennsylvania Medicaid and Dually Eligible Enrollees.

While clozapine is the most effective antipsychotic treatment for treatment-resistant schizophrenia, it remains underutilized across the United States, warranting a more comprehensive understanding of variation in use at the county level, as well as characterization of existing prescribing patterns. Here, we examined both Medicaid and Medicare databases to (1) characterize temporal and geographic variation in clozapine prescribing and, (2) identify patient-level characteristics associated with clozapine use. We included Medicaid and Fee for Service Medicare data in the state of Pennsylvania from January 1, 2013, through December 31, 2019. We focused on individuals with continuous enrollment, schizophrenia diagnosis, and multiple antipsychotic trials. Geographic variation was examined across counties of Pennsylvania. Regression models were constructed to determine demographic and clinical characteristics associated with clozapine use. Out of 8,255 individuals who may benefit from clozapine, 642 received treatment. We observed high medication burden, overall, including multiple antipsychotic trials. We also identified variation in clozapine use across regions in Pennsylvania with a disproportionate number of prescribers in urban areas and several counties with no identified clozapine prescribers. Finally, demographic, and clinical determinants of clozapine use were observed including less use in people identified as non-Hispanic Black, Hispanic, or with a substance use disorder. In addition, greater medical comorbidity was associated with increased clozapine use. Our work leveraged both Medicaid and Medicare data to characterize and surveil clozapine prescribing. Our findings support efforts monitor disparities and opportunities for the optimization of clozapine within municipalities to enhance clinical outcomes.

Development of an individualized risk calculator of treatment resistance in patients with first-episode psychosis (TRipCal) using automated machine learning: a 12-year follow-up study with clozapine prescription as a proxy indicator.

About 15-40% of patients with schizophrenia are treatment resistance (TR) and require clozapine. Identifying individuals who have higher risk of development of TR early in the course of illness is important to provide personalized intervention. A total of 1400 patients with FEP enrolled in the early intervention for psychosis service or receiving the standard psychiatric service between July 1, 1998, and June 30, 2003, for the first time were included. Clozapine prescriptions until June 2015, as a proxy of TR, were obtained. Premorbid information, baseline characteristics, and monthly clinical information were retrieved systematically from the electronic clinical management system (CMS). Training and testing samples were established with random subsampling. An automated machine learning (autoML) approach was used to optimize the ML algorithm and hyperparameters selection to establish four probabilistic classification models (baseline, 12-month, 24-month, and 36-month information) of TR development. This study found 191 FEP patients (13.7%) who had ever been prescribed clozapine over the follow-up periods. The ML pipelines identified with autoML had an area under the receiver operating characteristic curve ranging from 0.676 (baseline information) to 0.774 (36-month information) in predicting future TR. Features of baseline information, including schizophrenia diagnosis and age of onset, and longitudinal clinical information including symptoms variability, relapse, and use of antipsychotics and anticholinergic medications were important predictors and were included in the risk calculator. The risk calculator for future TR development in FEP patients (TRipCal) developed in this study could support the continuous development of data-driven clinical tools to assist personalized interventions to prevent or postpone TR development in the early course of illness and reduce delay in clozapine initiation.

Non-prescribing of clozapine for outpatients with schizophrenia in real-world settings: The clinicians’ perspectives

Clozapine is the gold standard for treating treatment-resistant schizophrenia although continuously underutilized. Previous surveys of clinicians have found that some of the most frequently cited barriers to clozapine prescribing are related to the blood-monitoring requirements. However, these surveys tend to explore general perspectives and may not reflect the true impact of different barriers in real-world outpatient settings. This study aimed to explore this issue. First, by surveying the clinicians responsible for the treatment of 39 clozapine-eligible, yet clozapine-naive, outpatients with schizophrenia. Then, based on the survey results, explanatory interviews with the participating psychiatrists were conducted and analyzed thematically. The most frequently cited reason for non-prescribing of clozapine was the expected non-compliance with blood-monitoring requirements; however, overall stability and/or severe mental illness was chosen as the most important reason in most patient-cases. The qualitative analysis highlighted the combined impact of standard clinical practice, personal experiences, and organizational constraints on clozapine utility.

Patient safety: adverse effects of Clozapine and their management at the Psychiatric Hospital Ghrasia in Yogyakarta, Indonesia.

Clozapine is an atypical antipsychotic indicated for treating patients resistant to antipsychotic therapy when other medications in this class have no therapeutic effect. Clozapine has greater efficacy but more side effects than other atypical antipsychotics (e.g., agranulocytosis, seizures, sedation, and weight gain). Side effects can cause discomfort to patients and can affect patient compliance, interfering with therapeutical outcomes. This study aims to identify the side effects of clozapine use in patients at the Psychiatric Hospital Grhasia, in Yogyakarta, Indonesia. Using a cross-sectional design, this research provides a retrospective descriptive analysis using medical records of patients at the Psychiatric Hospital Ghrasia Yogyakarta. Inpatient and outpatient medical records of patients who had received a clozapine prescription from January to December 2019 were analyzed. In the 336 patients that met the inclusion criteria, the incidence of side effects from clozapine use was 16.07% (95%, CI:2.2-4.1), with the most frequent being dizziness, vomiting, diarrhea, and hypersalivation. There was no effect of age, gender, profession, or patient's disease on their incidence. The management of side effects is classified into three aspects: the drug is stopped, the patient is given additional therapy, and the patient is not given therapy. The results showed that the use of clozapine at the Psychiatric Hospital Ghrasia Yogyakarta was relatively safe. Identification of side effects is necessary to determine the follow-up treatment.

Influence of time to clozapine prescription on the clinical outcome

BackgroundThis study investigates whether early clozapine use is associated with improved responses in different clinical domains, including positive and negative symptoms, functioning, and well-being. MethodsData from 254 clozapine-treated patients at Cambridgeshire and Peterborough NHS Foundation Trust (CPFT) were analysed. Among them, 231 (90.9 %) had a diagnosis of schizophrenia, 21 (8.3 %) schizoaffective disorder, and 2 (0.8 %) had other diagnoses. The International Classification of Diseases-Mortality and Morbidity Statistics criteria (ICD-10) were employed (World Health Organization, 1992). The cohort was assessed using the positive and negative syndrome scale (PANSS), the Brief Negative Symptom Scale (BNSS), Global Assessment of Functioning Scale (GAF), and the short version of Warwick-Edinburgh Mental Well-being Scale (SWEMWBS). Logistic regression models (for positive and negative symptom remission) and linear regression (for functioning and well-being) were utilized to assess the influence of time to clozapine initiation (TCI), age at the first episode of psychosis (AFE), duration of clozapine treatment (DCT), and gender. ResultsEarly clozapine treatment (within the first three years after the first episode of psychosis) was associated with increased negative symptom remission (exp (B) = 0.38; p = 0.02) and higher functioning scores (β = −0.12, p = 0.046). However, no effect of time to clozapine initiation was found on positive symptom remission rates or well-being scores. ConclusionsInitiating clozapine treatment within the first 3 years of the first episode of psychosis may lead to reduced severity of negative symptoms and improved functioning in clozapine-treated patients. The time to clozapine initiation did not influence its effect on positive symptom remission rates.

Clozapine dosing patterns and clinical outcomes in patients with treatment resistant schizophrenia

Clozapine is the only medication found to be effective for patients with treatment resistant schizophrenia-spectrum disorders (TRS) and its prescription patterns may impact on their outcomes. The study aims to explore the impact of clozapine dosing frequency, dose level and presence of pharmacological augmentation on the clinical, social and cognitive outcomes in patients with TRS. Patients with TRS and on clozapine were interviewed. Daily defined dose (DDD) and anticholinergic burden were calculated. Patients were categorized in three ways: the single daily dose (SDD) and multiple daily dose (MDD), ≤300 mg/day (LD) and >300 mg/day (HD) of clozapine, and clozapine monotherapy (MT) and augmentation therapy (AT). The impact of these clozapine prescription patterns and their interaction on patient outcomes were examined with ANOVA. Of 124 patients on clozapine, 98 patients (79%) had SDD, 59 patients (47.6%) received LD, and 58 patients (46.8%) had MT. Patients in the LD group had significantly better cognitive functions. Though no significant effect of clozapine dosing frequency on outcomes, among patients on LD, those on MDD had better processing speed, short-term and visual memory. Patients with MT had better motivation. Among patients on HD, those with MT had better motivation and vocational functioning. These results provide guidance to the clozapine prescription in a naturalistic setting to achieve optimizing outcomes for patients with TRS in social and cognitive functions. Further longitudinal studies are needed to verify the results.

Nationwide study on antipsychotic polypharmacy among forensic psychiatric patients

ABSTRACT This nationwide retrospective cross-sectional study examines the prevalence of antipsychotic polypharmacy (APP) and demographic, forensic, and clinical factors associated with its practice among Greenlandic forensic psychiatric patients. We collected data from electronic patient files, court documents, and forensic psychiatric assessments. We defined APP as two or more concurrent prescriptions of antipsychotic medication. The study population of 74 patients had a mean age of 41.4 years, and 61 were men. All included patients had either schizophrenia or another ICD-10 F2-diagnosis. We used unpaired t-tests and Chi2 or Fisher’s exact test. The prevalence of APP was 35% (n = 26), and there was a significant association between APP and a prescription of clozapine (Chi2, p = 0.010), olanzapine (Fisher’s test, p = 0.003), and aripiprazole (Fisher’s test, p = 0.013). Furthermore, we found a significant association between APP and prescription of a first-generation antipsychotic (FGA) (Chi2, p = 0.011). Despite recommendations in guidelines, the use of APP is common practice. The majority of forensic psychiatric patients suffer from severe psychiatric disorders, often with other comorbidities, including substance use disorder. The severity and complexity in mental health render forensic psychiatric patients at high risk of APP treatment. Further knowledge on APP use is crucial to secure and further improve the psychopharmacological treatment for this group of patients.

Adverse drug reactions and their fatal outcomes in clozapine patients in VigiBase: Comparing the top four reporting countries (US, UK, Canada and Australia)

BackgroundPharmacovigilance findings and box warnings in the clozapine package inserts have marked the history of clozapine. ObjectiveThis is the largest review of clozapine adverse drug reactions (ADRs) and their associated fatal outcomes. Reports to the World Health Organization's global pharmacovigilance database, VigiBase™, were analyzed, extending from clozapine's introduction to December 31, 2022. MethodsThe analysis focused on the top four reporting countries: United States (US), United Kingdom (UK), Canada and Australia (83 % of fatal outcomes worldwide). Attempts were made to control for population and clozapine prescription in each country. ResultsClozapine ADRs worldwide accounted for 191,557 reports, with the highest number (53,505) in “blood and lymphatic system disorder”. Of the 22,596 fatal outcomes reported in clozapine patients, 9587 were from the US, 6567 from the UK, 3623 from Canada and 1484 from Australia. The top category worldwide in fatal outcomes was nonspecifically labeled “death” with 46 % (range 22–62 %). “Pneumonia” was second with 30 % (range 17–45 %). Agranulocytosis was numerically only the 35th top clozapine ADR associated with fatal outcomes. On average, 2.3 clozapine ADRs were reported per fatal outcome. Infections were associated with 24.2 % of the UK fatal outcomes (9.4 %–11.9 % in the 3 other countries). ConclusionsThe four countries appeared to report clozapine ADRs in different ways, making comparisons difficult. We estimated higher fatal outcomes in the UK and Canada after controlling for cross-sectional estimations of population and published clozapine use. This last hypothesis is limited by the lack of precise estimation of accumulated clozapine use in each country.

Escaping the Long Shadow Cast by Agranulocytosis: Reflections on Clozapine Pharmacovigilance Focused on the United Kingdom.

A recent article in this journal presented a US perspective regarding the modernization of clozapine prescription and proposed an escape from the long shadow cast by agranulocytosis. Here, an international group of collaborators discusses a point of view complementary to the US view by focusing on worldwide outcomes of clozapine usage that may be uneven in terms of frequency of clozapine adverse drug reactions. Studies from the Scandinavian national registries (Finland and Denmark) did not find increased mortality in clozapine patients or any clear evidence of the alleged toxicity of clozapine. Data on clozapine-associated fatal outcomes were obtained from 2 recently published pharmacovigilance studies and from the UK pharmacovigilance database. A pharmacovigilance study focused on physician reports to assess worldwide lethality of drugs from 2010 to 2019 found 968 clozapine-associated fatal outcomes in the United Kingdom. Moreover, the United Kingdom accounted for 55% (968 of 1761) of worldwide and 90% (968 of 1073) of European fatal clozapine-associated outcomes. In a pharmacovigilance study from the UK database (from 2008 to 2017), clozapine was associated with 383 fatal outcomes/year including all reports from physicians and nonphysicians. From 2018 to 2021, UK clozapine-associated fatal outcomes increased to 440/year. The interpretation of fatal outcomes in each country using pharmacovigilance databases is limited and only allows gross comparisons; even with those limitations, the UK data seem concerning. Pneumonia and myocarditis may be more important than agranulocytosis in explaining the uneven distribution of fatal outcomes in clozapine patients across countries.

Clozapine prescription rates in Southeast Europe: A cross-sectional study.

International reports indicate that clozapine is under prescribed. Yet, this has not been explored in Southeast European (SEE) countries. This cross-sectional study investigates clozapine prescription rates in a sample of 401 outpatients with psychosis from Bosnia and Herzegovina, Kosovo by United Nations resolution, North Macedonia, Montenegro and Serbia. Descriptive analysis was used to explore clozapine prescription rates; daily antipsychotic dosage was calculated and converted into olanzapine equivalents. Patients receiving clozapine were compared to those not receiving clozapine; next those that were on clozapine monotherapy were compared to those who were on clozapine polytherapy regime. It was showed that clozapine was prescribed to 37.7% of patients (with cross-country variation: from 25% in North Macedonia to 43.8% in Montenegro), with average dose of 130.7 mg/daily. The majority of patients on clozapine (70.5%) were prescribed at least one more antipsychotic (the most frequent combination was with haloperidol). Our findings suggested that clozapine prescription rate in SEE outpatients is higher than in Western Europe. The average dose is significantly below the optimal therapeutic dosage recommended by clinical guidelines, and clozapine polytherapy is common. This might indicate that clozapine is prescribed mainly for its sedative effect rather than antipsychotic. We hope that this finding will be taken up by relevant stakeholders to address this non-evidence-based practice.

Clozapine use at a specialised psychiatric hospital in Johannesburg.

Clozapine is the gold standard medication for treatment-resistant psychosis, with robust evidence supporting its efficacy in multiple symptom domains. However, clozapine's side effect profile contributes to its underutilisation and discontinuation. This study aimed to explore the magnitude of clozapine use and describe factors that impact on its effective use among in-patients. Tara Hospital, a specialised psychiatric hospital in Johannesburg. This was a retrospective, cross-sectional file review of clozapine-treated patients admitted over the 2-year study period. Data variables included: demographics, clinical information, discharge prescription, clozapine-related side effects and details of clozapine discontinuation, where applicable. A cohort of 33.2% of patients from Tara's biological wards received a trial of clozapine. Participants experienced anti-cholinergic clozapine-related side effects that included weight gain (79.5%), tachycardia (35.2%) and constipation (35.2%). Clozapine was discontinued in 13.7% of participants, and no life-threatening side effects or deaths occurred. Significantly more use of flupenthixol decanoate (64.3% vs. 30.7%; p = 0.0322) and anticholinergics (35.7% vs. 11.4%; p = 0.0474) occurred in the clozapine-discontinued group. Polypharmacy rates were high for psychiatric and non-psychiatric medications. One-third of patients received clozapine trials, most of whom continued at discharge. Although side effects occurred frequently, life-threatening side effects did not. Clozapine monitoring protocols, side effect rating scales, pre-emptive management of side effects, lifestyle interventions and clinician education may improve outcomes of clozapine use. The use of plasma clozapine levels may be beneficial. This study expands our limited knowledge regarding current clozapine prescribing trends in South Africa.

Clinician’s attitude towards clozapine prescription

IntroductionCurrent clinical guidelines recommend the use of clozapine for the treatment of refractory schizophrenia, present in up to a third of patients with this disease. Despite the evidence, the data point to low prescription, underdosing, and delayed initiation.ObjectivesThe objective of the study is to elucidate which factors may interfere in clozpine prescription.MethodsThis is a cross-sectional observational study, carried out using a survey designed specifically for it.It was answered online by seventy psychiatrists affiliated with the Catalan Society of Psychiatry.ResultsMore than half admitted having prescribed two or more antipsychotics without having previously ruled out pseudorefractoriness through depot treatment. 70% recognized the need for monitoring as the main prescription barrier, while the main reason for withdrawal was its adverse effects. The most alarming was considered agranulocytosis, with drooling, drowsiness and weight gain being the most reported.Statistically significant differences (p=0.031) were found in relation to the years of experience and the device where clozapine was preferred to be started: <10 years in hospital, 10-20 years in partial hospitalization and >20 years outpatient office.Statistically significant differences were observed in the preference of the device for its initiation depending on the usual work device: hospitalization (p<0.000) and partial hospitalization (p=0.046) preferred to schedule it from their respective devices, without any preference in consultations.The level of experience and the most reported side effect were statistically significant: for the newest psychiatrists it was weight gain (p=0.031), without presenting differences in the rest of the groups.ConclusionsClozapine is the psychoactive drug of choice in refractory schizophrenia, so efforts should be devoted to reducing prescription barriers, offering training on its management and innovating forms of monitoring to promote its use.Disclosure of InterestNone Declared

Two-year cohort-up study of clozapine prescription in Chinese patients with schizophrenia treated in rural primary care.

Few studies have examined the 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 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 generalized estimating equation (GEE). In this study, 742 patients with schizophrenia were invited, and 491 completed the two-year follow-up study. Being married, more years of education, more waist circumference, using mood stabilizer, using anticholinergic, higher ITAQ (Insight and Treatment Attitude Questionnaire) scores were more significantly related to the use of 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 price of drugs, clinical factors, health regulations, and the characteristics of treatment environment. Further examination of the rationale and appropriateness of clozapine in primary care in China is necessary.