Clozapine is the antipsychotic of choice for people with treatment-resistant schizophrenia (TRS) but is associated with the uncommon but potentially life-threatening adverse effect of myocarditis. However, there are no criteria for diagnosing clozapine-associated myocarditis (CAM) or global guidelines on detection and risk reduction, or for restarting clozapine after CAM.

To develop criteria for CAM and algorithms for clozapine initiation and clozapine rechallenge after CAM in a multiprofessional consensus process.

We conducted a systematic literature search for cases of clozapine rechallenge following CAM using the PubMed, EMBASE, CINAHL and PsycINFO databases, followed by a multidisciplinary international two-step Delphi consensus process in July and October 2024. The Delphi panel comprised psychiatrists, cardiologists, pharmacists, psychopharmacologists and nurses with expertise on clozapine or myocarditis.

Ninety-three clinicians and academics with experience in prescribing clozapine from six continents participated in the Delphi process. A consensus was reached on a definition of CAM according to modified clinical criteria from the European Society of Cardiology for myocarditis associated with immune checkpoint inhibitors. Titration schemes slower than those given in the Summary of Product Characteristics for clozapine were recommended to minimise CAM risk. Minimum and enhanced requirements for screening and monitoring were developed to account for global perspectives and limited resources in certain healthcare systems, and an approach to clozapine rechallenge was elaborated.

This multidisciplinary project represents the first guidance for CAM and will inform clinicians, other caregivers and patients, as well as facilitating the development of national guidelines on CAM prevention, screening and monitoring and rechallenge after an index episode of myocarditis in individuals taking clozapine.

Improved understanding of the cognitive and behavioural processes underpinning panic disorder (PD) in adolescents could improve identification and treatment.

We investigated whether the processes outlined in Clark’s (1986) cognitive model of PD are observed in adolescents with PD, are specific to PD, and predict symptom severity.

We recruited three groups of adolescents (12–17 years): 34 with a PD diagnosis, 33 with another anxiety disorder excluding PD (‘clinical control’), and 34 scoring below the clinical cut-off on a measure of anxiety symptoms (‘community control’). Participants self-reported on measures of PD symptom severity, catastrophic cognitions, bodily sensation fear, and safety-seeking behaviours.

The PD group reported significantly higher levels of catastrophic cognitions and safety-seeking behaviours than both control groups. They reported significantly higher levels of bodily sensation fear compared with the community but not the clinical control group. All process measures positively predicted PD symptom severity across all groups.

We found evidence of catastrophic cognitions and safety-seeking behaviours as PD-specific processes in adolescents which predict symptom severity. Bodily sensation fear also predicted symptom severity. Findings support Clark’s cognitive model of PD in adolescents and suggest that catastrophic cognitions and safety behaviours may be targets for adolescent PD treatment.

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.

Community treatment order (CTO) use in Australia and New Zealand ranges from less than 40 per 100 000 population in Western Australia and Canterbury to over 100 per 100 000 in Victoria, South Australia and Waitemata. Recent publications on CTO use now permit a meta-regression to investigate whether differences in CTO use by jurisdiction affect either the possible predictors or outcomes of CTOs.

To assess whether factors associated with CTO placement or subsequent outcomes vary by rates of use.

A systematic search of PubMed/Medline, Embase, CINAHL, the Cochrane Central Register of Controlled Trials and PsycINFO for any Australian or New Zealand study comparing CTO cases with controls receiving voluntary psychiatric treatment. This study was prospectively registered with PROSPERO (protocol registration number: CRD42022351500).

There were 35 articles from 16 studies identified in the search, plus unpublished data from a further study. Of these, 29 publications were included in meta-analyses. Two were from New Zealand. People who were male, single and not engaged in work, study or home duties were significantly more likely to be on CTOs. In addition, those from migrant backgrounds were 47% more likely to be on an order. On meta-regression, cases in jurisdictions with higher CTO rates had higher proportions of females or individuals with diagnoses other than non-affective psychoses. High-use jurisdictions were also less likely to show reductions in readmission rates or bed-days.

There are marked differences in the possible predictors and outcomes of CTO placement between high- and low-use jurisdictions in Australia and New Zealand. These findings may have implications elsewhere and indicate that better-targeted CTO placement might improve outcomes.

Clozapine is the most effective medication for treatment-refractory schizophrenia but is associated with significant adverse drug reactions, including nocturnal enuresis and urinary incontinence. This side effect can be burdensome and lead to medication nonadherence and psychotic relapse. Evidence to guide treatment of clozapine-induced nocturnal enuresis and urinary incontinence is sparse. We therefore aimed to synthesize the evidence base to guide management for clinicians, patients, and their carers.

We systematically searched PubMed, Embase, PsycInfo, CINAHL, and the Cochrane Trial Registry databases from inception to May 2021 for publications on management of clozapine-induced nocturnal enuresis and urinary incontinence using a PROSPERO preregistered search strategy.

We identified 22 case reports and case series describing 74 patients. Interventions included clozapine dose reduction, nonpharmacological treatment, and pharmacological treatments. Among pharmacological treatments, desmopressin, oxybutynin, trihexyphenidyl, tolterodine, imipramine, amitriptyline, ephedrine, pseudoephedrine, aripiprazole, and verapamil were associated with complete resolution of nocturnal enuresis and urinary incontinence. Balancing evidence for effectiveness against risk of adverse effects, we developed a management framework for clozapine-induced nocturnal enuresis and urinary incontinence.

Following assessment of urological, psychiatric, pharmacological, and common comorbid medical issues, first-line treatments should be nonpharmacological, including bathroom alarms, voiding before bedtime, and nocturnal fluid restriction. If these interventions do not provide adequate relief, aripiprazole should be trialed. Desmopressin may be considered for severe refractory cases, but monitoring for hyponatremia is essential.