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Background: There is evidence of heterogeneity within treatment-resistant schizophrenia (TRS), with some people not responding to antipsychotic treatment from illness onset and others becoming treatment-resistant after an initial response period. These groups may have different aetiologies., Aim: This study investigates sociodemographic and clinical correlates of early onset of TRS., Method: Employing a retrospective cohort design, we do a secondary analysis of data from a cohort of people with TRS attending the South London and Maudsley. Regression analyses were conducted to identify the correlates of the length of treatment to TRS. Predictors included the following: gender, age, ethnicity, problems with positive symptoms, problems with activities of daily living, psychiatric comorbidities, involuntary hospitalisation and treatment with long-acting injectable antipsychotics., Results: In a cohort of 164 people with TRS (60% were men), the median length of treatment to TRS was 3 years and 8 months. We observed no cut-off on the length of treatment until TRS presentation differentiating between early and late TRS (i.e. no bimodal distribution). Having mild to very severe problems with hallucinations and delusions at the treatment start was associated with earlier TRS (~19 months earlier). In sensitivity analyses, including only complete cases (subject to selection bias), treatment with a long-acting injectable antipsychotic was additionally associated with later TRS (~15 months later)., Conclusion: Our findings do not support a clear separation between early and late TRS but rather a continuum of the length of treatment before TRS onset. Having mild to very severe problems with positive symptoms at treatment start predicts earlier onset of TRS.

Introduction: The Prescribing Observatory for Mental Health initiated a quality improvement (QI) programme on clozapine use in UK mental health services., Methods: Clinical audits conducted in 2019 and 2021., Results: Sixty-three participating NHS Trusts/healthcare organisations in 2019, and 61 in 2021, submitted treatment data for 6948 and 8155 patients, respectively. In both audits, high-dose and/or combined antipsychotic medications had been prescribed immediately before initiating clozapine in over a quarter of patients recently started on clozapine. In patients who were tobacco smokers and recently discharged from a smoke-free ward, the impact of the potential change in smoking status had been considered in the care plans of just under one-third in 2019 and just over a half in 2021. For community patients, their Summary Care Records (SCRs) included their clozapine prescriptions in 58% of cases in 2019 and 72% in 2021., Conclusions: Three QI issues were identified. (1) Antipsychotic regimens with limited evidence for efficacy in treatment-resistant schizophrenia were prescribed for over a quarter of cases before starting clozapine. Use of such strategies may delay clozapine treatment, potentially reducing the likelihood of a therapeutic response. (2) While anticipation of the consequences of a change in smoking status on plasma clozapine concentration following discharge from hospital showed improvement over time, even in 2021 it was not evident for nearly a half of relevant cases. (3) While inclusion of clozapine in the SCR also improved over time, even in 2021 it was missing for more than a quarter of community patients.

Background: A proportion of people with treatment-resistant schizophrenia fail to show improvement on clozapine treatment. Knowledge of the sociodemographic and clinical factors predicting clozapine response may be useful in developing personalised approaches to treatment., Methods: This retrospective cohort study used data from the electronic health records of the South London and Maudsley (SLaM) hospital between 2007 and 2011. Using the Least Absolute Shrinkage and Selection Operator (LASSO) regression statistical learning approach, we examined 35 sociodemographic and clinical factors' predictive ability of response to clozapine at 3 months of treatment. Response was assessed by the level of change in the severity of the symptoms using the Clinical Global Impression (CGI) scale., Results: We identified 242 service-users with a treatment-resistant psychotic disorder who had their first trial of clozapine and continued the treatment for at least 3 months. The LASSO regression identified three predictors of response to clozapine: higher severity of illness at baseline, female gender and having a comorbid mood disorder. These factors are estimated to explain 18% of the variance in clozapine response. The model's optimism-corrected calibration slope was 1.37, suggesting that the model will underfit when applied to new data., Conclusions: These findings suggest that women, people with a comorbid mood disorder and those who are most ill at baseline respond better to clozapine. However, the accuracy of the internally validated and recalibrated model was low. Therefore, future research should indicate whether a prediction model developed by including routinely collected data, in combination with biological information, presents adequate predictive ability to be applied in clinical settings.

Background: The use of clozapine demands regular monitoring of clozapine plasma concentrations and of white blood cell parameters. The delay between sending blood samples for analysis and receiving the results hinders clinical care. Point-of-care testing (POCT) can provide drug assay results within a few minutes., Aim: This study aimed to investigate the utility of a novel point-of-care device that can measure clozapine concentrations using capillary blood samples collected via a finger stick., Method: During a five-week period starting in June 2019 eligible patients were asked to provide a finger-stick capillary sample in addition to their usual venous blood sample. Samples were analysed by the novel point-of-care device and by the standard laboratory method. Capillary blood samples were tested by the MyCare™ Insite POCT analyser, and a quantitative measurement of clozapine concentration was provided within six minutes., Results: A total of 309 patients agreed to measurements by the two methods. Analysis revealed clozapine concentrations in venous blood as determined by the laboratory method ranged from 20 to 1310 ng/mL and by POCT from 7 to 1425 ng/mL. There was a strong positive correlation ( R  = 0.89) between the results from the venous and the capillary sample methods. The slope of the association between standard assay and MyCare™ Insite was 1.0 with an intercept of -21 ng/mL, indicating minimal bias., Conclusion: Clozapine concentrations can be accurately measured at the point of care using capillary blood samples collected via a finger stick. This approach may be more acceptable than venous sampling to patients and, with almost instant results available, more useful to clinicians.

These updated guidelines from the British Association for Psychopharmacology replace the original version published in 2011. They address the scope and targets of pharmacological treatment for schizophrenia. A consensus meeting was held in 2017, involving experts in schizophrenia and its treatment. They were asked to review key areas and consider the strength of the evidence on the risk-benefit balance of pharmacological interventions and the clinical implications, with an emphasis on meta-analyses, systematic reviews and randomised controlled trials where available, plus updates on current clinical practice. The guidelines cover the pharmacological management and treatment of schizophrenia across the various stages of the illness, including first-episode, relapse prevention, and illness that has proved refractory to standard treatment. It is hoped that the practice recommendations presented will support clinical decision making for practitioners, serve as a source of information for patients and carers, and inform quality improvement.

Background: Insight into the effect of clozapine is limited by a lack of controlling for confounding variables in current research. Our objective was to investigate the association between clozapine prescribed at discharge, following an inpatient episode, and risk of readmission into secondary mental health services in patients with schizophrenia and schizoaffective disorder, controlling extensively for confounding variables., Methods: Clinical records from 3651 patients were analysed in a retrospective observational cohort study. Cox proportional-hazards regression models were used to assess the risk of hospital readmission. A series of sensitivity analyses were also conducted. Propensity score methods were used to address confounding-by-indication., Results: Patients on clozapine ( n=202) had a reduced risk of readmission compared with patients on other antipsychotics (adjusted hazard ratio=0.79; 95% confidence interval: 0.64-0.99; p=0.043). Clozapine also had a protective effect on risk of readmission when compared with olanzapine (adjusted hazard ratio 0.76; 95% confidence interval: 0.60-0.96; p=0.021). The effect size remained consistent after adjusting for an array of possible confounders, as well as using propensity scores to address confounding-by-indication. A statistically significant result was also noted in all but two sensitivity analyses., Conclusion: Our findings suggest that clozapine is associated with a reduced risk of readmission into secondary mental health services.

Rationale: Antipsychotic polypharmacy (APP) is commonly used in schizophrenia despite a lack of robust evidence for efficacy, as well as evidence of increased rates of adverse drug reactions and mortality., Objectives: We sought to examine APP and the use of other adjunctive medications in patients with treatment-resistant schizophrenic disorders (ICD-10 diagnoses F20-F29) immediately prior to clozapine initiation, and to investigate clinical and sociodemographic factors associated with APP use in this setting., Methods: Analysis of case notes from 310 patients receiving their first course of clozapine at the South London and Maudsley NHS Trust (SLaM) was undertaken using the Clinical Record Interactive Search (CRIS) case register. Medication taken immediately prior to clozapine initiation was recorded, and global clinical severity was assessed at time points throughout the year prior to medication assessment using the Clinical Global Impression - Severity scale (CGI-S). Logistic regression was used to investigate factors associated with APP., Results: The point prevalence of APP prior to clozapine initiation was 13.6% (n=42), with 32.6% of subjects prescribed adjuvant psychotropic medications. APP was associated with increasing number of adjuvant medications (odds ratio (OR) 1.97, 95% confidence interval (CI) 1.27-3.06), concurrent depot antipsychotic prescription (OR 2.64, CI 1.24-5.62), concurrent antidepressant prescription (OR 4.40, CI 1.82-10.63) and a CGI-S over the previous year within the two middle quartiles (Quartile 2 vs 1 OR 6.19, CI 1.81-21.10; Quartile 3 vs 1 OR 4.45, CI 1.29-15.37; Quartile 4 vs 1 OR 1.88, CI 0.45-7.13)., Conclusions: APP and augmentation of antipsychotics with antidepressants, mood stabilizers and benzodiazepines are being employed in treatment-resistant schizophrenia prior to clozapine. The conservative APP rate observed may have been influenced by an initiative within SLaM that reduced APP rates during the study window. Efforts to reduce the use of poorly evidenced prescribing should focus on adjuvant medications as well as APP., (© The Author(s) 2016.)

Clozapine is the treatment of choice for treatment-resistant schizophrenia, but it is associated with a risk of neutropaenia and agranulocytosis. Clozapine use is regulated by mandatory blood monitoring in the UK, requiring cessation of treatment should the absolute neutrophil count (ANC) drop below specified values. Benign reductions in the ANC in non-white populations are common, and this can preclude a patient from receiving treatment with clozapine. A diagnosis of benign ethnic neutropaenia can reduce these treatment restrictions (UK specific), but the degree of neutropaenia can be significant enough to still prevent treatment. In this report, we show that response to granulocyte colony stimulating factor (G-CSF) may be quite variable and difficult to predict, but with careful monitoring it can be used to increase the ANC count and allow continued treatment with clozapine.