Clozapine is the antipsychotic medication with the greatest efficacy in treatment-resistant schizophrenia (TRS). Unfortunately, clozapine is ceased in approximately 0.2% to 8.5% of people due to concerns about clozapine-associated myocarditis (CAM). The opportunity for clozapine rechallenge is important for people with TRS and CAM, due to limited alternative treatments. However, there is a lack of consensus regarding the optimal process, monitoring, and dose titration to achieve successful clozapine rechallenge. The study aimed to review the process, monitoring, and dose titration within cases of clozapine rechallenge after CAM, to identify features associated with successful rechallenge.

A systematic review of clozapine rechallenge cases following CAM was conducted. PubMed, EMBASE, Cinahl, and PsycINFO were searched for cases. Reference lists of retrieved articles and field experts were consulted to identify additional studies.

Forty-five cases were identified that described clozapine rechallenge, 31 of which were successful. Successful rechallenge cases generally used a slower dose titration regime with more frequent monitoring than standard clozapine initiation protocols; however, this data was not always completely recorded within cases. Six cases referred to published rechallenge protocols to guide their rechallenge.

The process, monitoring, and dose titration of clozapine rechallenge are inconsistently reported in the literature. Despite this, 69% of case reports detailed a successful rechallenge post CAM; noting limitations associated with reliance on case data. Ensuring published clozapine rechallenge cases report standardised data, including titration speed and monitoring frequencies, is required to guide the development and validation of guidelines for clozapine rechallenge.

Most evidence on associations between child maltreatment and subsequent common mental disorders (CMDs) comes from retrospective studies. Such findings may be affected by recall bias. Prospective studies of reports to statutory agencies are less common and may be subject to attrition bias.

To examine the associations of child maltreatment with emergency department presentations and in-patient admissions for CMDs in individuals up to 40 years old.

Queensland-wide administrative health data were linked to a prospective birth cohort, including agency-reported and substantiated notifications of child maltreatment. Outcomes were emergency department presentations and in-patient admissions for CMDs.

There were 6087 participants, of which 10.1% had been the subject of a child maltreatment notification. Admissions for CMDs occurred in 198 participants (3.3%) and emergency department presentations in 291 (4.8%). In the adjusted analysis, substantiated child maltreatment was associated with both admissions (odds ratio 1.92; 95% CI = 1.19–3.00) and emergency department presentations (odds ratio 2.10; 95% CI = 1.45–3.03). All agency-reported and substantiated child maltreatment subtypes (neglect, physical, sexual and emotional abuse) were associated with emergency department presentations for CMDs and notifications for more than one child maltreatment subtype. In the subgroup analysis, child maltreatment was associated with emergency department presentations for both anxiety (odds ratio 2.73; 95% CI = 1.68–4.43) and depression (odds ratio 2.23; 95% CI = 1.62–3.26) but with admissions only for depression (odds ratio 2.10; 95% CI = 1.15–3.84).

Child maltreatment is associated with both emergency department presentations and hospital admissions for CMDs in individuals up to 40 years old. Screening for child maltreatment in people presenting to hospital with CMDs may be indicated, as well as a greater awareness that survivors of child maltreatment may be at higher risk of developing such symptoms.

There is a high incidence of serious mental illness (SMI) and antipsychotic use in the respiratory high dependence unit (HDU) compared with the general population. However, there is a paucity of data in the extant literature evaluating the relationships between respiratory failure and antipsychotics.

To investigate the relationship between antipsychotics and respiratory failure in people admitted to a respiratory HDU, and to gain a better understanding of the potential impact of antipsychotic medications on respiratory outcomes.

Medical, demographic and clinical outcome data were collected for a consecutive sample of 638 individuals admitted to a respiratory HDU between the dates 1 January 2018 and 29 May 2021 at a large quaternary hospital.

Multivariate models controlling for confounders found that antipsychotic medications increased risk of admission for type 2 respiratory failure and chronic obstructive pulmonary disease exacerbation without hypercapnia by 3.7 and 11.45 times, respectively. For people admitted with type 2 respiratory failure, antipsychotic use increased the risk of requiring non-invasive ventilation by 4.9 times. Those prescribed an antipsychotic were more likely to be readmitted within 30 days. Over 30% of individuals were prescribed antipsychotics for an unlicensed indication.

Poor respiratory outcomes may be a previously unknown adverse drug reaction of antipsychotics. Modifications to clinical care and clinical pathways for those with SMI prescribed antipsychotic medications, including optimising their chronic health and deprescribing where appropriate, should be prioritised.

Although clozapine is the most effective antipsychotic for people with treatment-resistant schizophrenia (TRS), only 40% of people with TRS respond, and there is limited evidence for augmentation agents. Cannabidiol (CBD) reduces positive symptoms in individuals with schizophrenia, but no trials have specifically examined its efficacy in those with clozapine-resistant schizophrenia.

To examine the clinical efficacy of CBD augmentation in people with clozapine-resistant schizophrenia.

This is a 12-week randomised, placebo-controlled, double-blind, parallel-group trial (registration number: ACTRN12622001112752). We will recruit 88 individuals with clozapine-resistant schizophrenia, randomised (1:1) to 1000 mg daily CBD versus placebo. Eligible individuals will be aged between 18 and 64 years, fulfil DSM-IV criteria for schizophrenia or schizoaffective disorder, have a total PANSS (Positive and Negative Syndrome Scale) score ≥60, have received oral clozapine for at least 18 weeks and have a clozapine level of >350 ng/mL. Interim analyses will be conducted at 25, 50 and 75% recruitment; these will also provide an opportunity to reallocate participants dependent on conditional power. The primary endpoint will be the difference in PANSS positive scores at the end of week 12. Secondary endpoints include depression, anxiety, sleep, quality of life, alcohol consumption, change in weight and metabolic syndrome components, and neurocognitive measures, as well as safety and tolerability.

Novel treatments for clozapine-resistant schizophrenia are urgently needed. If found to be effective, CBD may have a role as a novel and safe adjunct to clozapine.

Severe mental illness (SMI) is associated with significant morbidity. Frailty combines biological ageing, comorbidity and psychosocial factors and can predict adverse health outcomes. Emerging evidence indicates that frailty is higher in individuals with SMI than in the general population, although studies have been limited by sample size.

To describe the prevalence of frailty in people with SMI in a large cohort using three different frailty measures and examine the impact of demographic and sociodemographic variables.

The UK Biobank survey data, which included individuals aged 37–73 years from England, Scotland and Wales from 2006 to 2010, with linked in-patient hospital episodes, were utilised. The prevalence of frailty in individuals with and without SMI was assessed through three frailty measures: frailty index, physical frailty phenotype (PFP) and Hospital Frailty Risk Score (HFRS). Stratified analysis and dichotomous logistic regression were conducted.

A frailty index could be calculated for 99.5% of the 502 412 UK Biobank participants and demonstrated greater prevalence of frailty in women and an increase with age. The prevalence of frailty for those with SMI was 3.19% (95% CI 3.0–3.4), 4.2% (95% CI 3.8–4.7) and 18% (95% CI 15–23) using the frailty index, PFP and HFRS respectively. The prevalence ratio was between 3 and 18 times higher than in those without SMI.

As a measure, frailty captures the known increase in morbidity associated with SMI and may potentially allow for earlier identification of those who will benefit from targeted interventions.

People with schizophrenia die almost 20 years earlier than the general population, most commonly from avertable cardiometabolic disease. Existing pharmacological weight-loss agents including metformin have limited efficacy. Recently available glucagon-like peptide (GLP-1) receptor agonists such as semaglutide have shown promise for weight loss but have yet to be trialled in this population.

To examine the efficacy of semaglutide to ameliorate antipsychotic-induced obesity in people with schizophrenia who have been treated with clozapine for more than 18 weeks.

This is a 36-week, double-blinded, randomised placebo-controlled trial. We will recruit 80 clozapine-treated patients with schizophrenia or schizoaffective disorder, aged 18–64 years, with a baseline body mass index ≥26 kg/m2, who will be randomised to subcutaneous semaglutide of 2.0 mg once a week or placebo for 36 weeks. The primary endpoint will be percentage change in body weight from baseline.

This trial will assess the efficacy and side-effects of the GLP-1 receptor agonist semaglutide on body weight and provide evidence on the possible clinical utility of semaglutide in patients with inadequate response to metformin. The study is registered with the Australian New Zealand Clinical Trials Registry (www.anzctr.org.au) with clinical trial registration number ACTRN12621001539820.

This research could benefit individuals with schizophrenia who experience significant health issues, leading to premature mortality, owing to antipsychotic-induced weight gain. Study findings will be disseminated through peer-reviewed publications and conference presentations.