Quality of melatonin use in children and adolescents: findings from a UK clinical audit.

BACKGROUND: Melatonin is commonly used to treat sleep disturbance in children and adolescents, although uncertainties about its optimal use remain. OBJECTIVE: To determine to what extent prescribing of melatonin complies with evidence-based clinical practice standards. METHODS: As part of a quality improvement programme, the Prescribing Observatory for Mental Health conducted a retrospective clinical audit in UK services for children and adolescents. FINDINGS: Data were submitted for 4151 children and adolescents up to 18 years of age, treated with melatonin: 3053 (74%) had a diagnosis of neurodevelopmental disorder. In 2655 (73%) of the 3651 patients prescribed melatonin to be taken regularly, the main reason was to reduce sleep latency (time taken to fall asleep). In 409 patients recently starting melatonin, a non-pharmacological intervention had already been tried in 279 (68%). The therapeutic response of patients early in treatment (n=899) and on long-term treatment (n=2353) had been assessed and quantified in 36% and 31%, respectively, while for review of side effects, the respective proportions were 46% and 43%. Planned treatment breaks were documented in 317 (13%) of those on long-term treatment. CONCLUSIONS: Melatonin was predominantly prescribed for evidence-based clinical indications, but the clinical review and monitoring of this treatment fell short of best practice. CLINICAL IMPLICATIONS: With limited methodical review of melatonin use in their patients, clinicians will fail to garner reliable information on its risks and benefits for individual patients. The lack of such practice-based evidence may increase the risk of melatonin being inappropriately targeted or continued despite being ineffective or no longer indicated.

Monitoring lithium therapy: the impact of a quality improvement programme in the UK.

OBJECTIVES: The study was designed to test an audit-based quality improvement programme (QIP) addressing lithium prescribing and monitoring in UK mental health services. METHODS: A baseline clinical audit was conducted against the following standards: (i) measurement of renal and thyroid function before initiating treatment with lithium and (ii) recommended monitoring of serum lithium and renal and thyroid function during maintenance treatment. A re-audit was conducted at 18 months and a supplementary audit at three years. RESULTS: Data were submitted for patients at baseline (n = 3,373), re-audit (n = 3,647), and supplementary audit (n = 5,683), 57% of whom had bipolar disorder. The baseline findings prompted a patient safety alert issued by the National Patient Safety Agency. By supplementary audit, the proportion of patients having four serum lithium tests over the previous year had increased from 30% at baseline to 48%, and the respective proportions that had two tests of renal function from 55% to 70% and thyroid function from 49% to 66%. Elderly patients and those prescribed a drug known to interact with lithium were not more likely to be monitored in line with the audit standards. Between baseline and supplementary audit, the proportion of patients with a diagnosis of bipolar disorder prescribed an antidepressant increased from 36% to 41%. CONCLUSIONS: Improvements in biochemical monitoring of lithium treatment were achieved over time with participation in a QIP that included benchmarking of performance against clinical standards and customized change interventions. Nevertheless, gaps remain between the standard and current practice. Antidepressants are frequently prescribed in patients with bipolar disorder despite a paucity of evidence supporting their efficacy.

Plus ça change? Switching lithium preparations.

AIMS AND METHOD: A supply disruption alert in 2020, now rescinded, notified UK prescribers of the planned discontinuation of Priadel® (lithium carbonate) tablets. This service evaluation explored lithium dose and plasma levels before and after the switching of lithium brands, in order to determine the interchangeability of different brands of lithium from a pharmacokinetic perspective. RESULTS: Data on the treatment of 37 patients switched from Priadel® tablets were analysed. Switching to Camcolit® controlled-release tablets at the same dose did not result in meaningful differences in plasma lithium levels. Dose adjustment and known or suspected poor medication adherence were associated with greater variability in plasma lithium levels on switching brands. CLINICAL IMPLICATIONS: For comparable pre- and post-switch doses in adherent patients, the most common brands of lithium carbonate appear to produce similar plasma lithium levels. British National Formulary guidance relating to switching lithium brands may be unnecessarily complex.

Management of medically assisted withdrawal from alcohol in acute adult mental health and specialist addictions in-patient services: UK clinical audit findings.

BACKGROUND: Medically assisted alcohol withdrawal (MAAW) is increasingly undertaken on acute adult psychiatric wards. AIMS: Comparison of the quality of MAAW between acute adult wards and specialist addictions units in mental health services. METHOD: Clinical audit conducted by the Prescribing Observatory for Mental Health (POMH). Information on MAAW was collected from clinical records using a bespoke data collection tool. RESULTS: Forty-five National Health Service (NHS) mental health trusts/healthcare organisations submitted data relating to the treatment of 908 patients undergoing MAAW on an acute adult ward or psychiatric intensive care unit (PICU) and 347 admitted to a specialist NHS addictions unit. MAAW had been overseen by an addiction specialist in 33 (4%) of the patients on an acute adult ward/PICU. A comprehensive alcohol history, measurement of breath alcohol, full screening for Wernicke's encephalopathy, use of parenteral thiamine, prescription of medications for relapse prevention (such as acamprosate) and referral for specialist continuing care of alcohol-related problems following discharge were all more commonly documented when care was provided on a specialist unit or when there was specialist addictions management on an acute ward. CONCLUSIONS: The findings suggest that the quality of care provided for medically assisted withdrawal from alcohol, including the use of evidence-based interventions, is better when clinicians with specialist addictions training are involved. This has implications for future quality improvement in the provision of MAAW in acute adult mental health settings.

Role of the prescribing observatory for mental health.

Positive change in prescribing practice in psychiatric services can be achieved with participation in the UK Prescribing Observatory for Mental Health (POMH-UK) quality improvement programmes. Key elements are feedback of benchmarked performance for local clinical reflection and customised change interventions informed by the national audit findings and parallel qualitative work. However, progress is gradual and gains generally modest.

Nocturnal enuresis with antipsychotic medication.

Nocturnal enuresis can be discomfiting and troublesome. There is increasing evidence that as a side-effect of second-generation antipsychotics, particularly clozapine, it may be underrecognised. Direct but sensitive questioning may be required to elicit this side-effect. We briefly review possible mechanisms of this problem, and management and treatment options.

Antipsychotics in dementia: prevalence and quality of antipsychotic drug prescribing in UK mental health services.

BACKGROUND: Up to a quarter of people in the UK with a diagnosis of dementia are prescribed an antipsychotic in any year. The potential risks of such treatment are becoming clearer, but the benefits remain uncertain. Concern about the frequency and quality of such prescribing was expressed in the National Dementia Strategy for England in 2009. AIMS: To provide an estimate of the prevalence of antipsychotic use for dementia in secondary mental health services in the UK and to collect data relevant to quality improvement initiatives for such prescribing practice. METHOD: In the context of a UK quality improvement programme, relevant clinical audit data were collected for patients with dementia under the care of specialist older people's mental health services. RESULTS: Fifty-four mental health National Health Service (NHS) trusts submitted data on 10 199 patients. Of those patients without comorbid psychotic illness, 1620 (16%) were prescribed an antipsychotic; the common clinical indications for such medication were agitation, psychotic symptoms, aggression and distress. Multivariable regression found younger age, care home or in-patient setting, vascular or Parkinson's disease dementia and greater severity of dementia to be all significantly associated with being prescribed antipsychotic medication. Of the 1001 (62%) patients prescribed treatment for more than 6 months, only three-quarters had a documented review of therapeutic response in the previous 6 months. CONCLUSIONS: The data reveal areas of relatively good current practice, including consideration of alternatives to antipsychotic medication and clear documentation of target symptoms. They also suggest areas for improvement, such as the frequency and quality of review of long-term medication. Strategies to reduce antipsychotic use should take account of the demographic and clinical variables predicting increased likelihood of antipsychotic prescription.

Patient Group Directions: a safe and effective practice?

Patient Group Directions (PGDs) have been used in clinical practice for a decade. They enable non-medical practitioners to supply medicines to patients, in certain legally defined circumstances, without a doctor's prescription and in accordance with a pre-defined protocol. The authors aimed to review the existing literature in order to identify and evaluate the evidence regarding the quality, safety and acceptability of PGDs within care systems and their impact on health outcomes. Searches of relevant databases were conducted, articles screened against eligibility criteria and relevant data extracted. A number of key issues emerged from the data including quality and safety of practice, acceptability to patients and practitioners, access to treatment and implications for professional roles and responsibilities. There were no data related to health outcomes. The review concludes that while PGDs may be an acceptable way to deliver care, their impact on patient outcomes and health status has been poorly studied.

Can the use of long-acting injectable antipsychotic preparations be increased in routine clinical practice and the benefits realised?

BACKGROUND: The use of continuing antipsychotic medication is an established evidence-based strategy for preventing relapse in people with schizophrenia, but medication adherence is known to be suboptimal. Covert non-adherence can be eliminated by the use of long-acting injectable (LAI) formulations. We sought to (1) raise awareness among clinicians of the potential benefits of LAI antipsychotic formulations, (2) increase use of these formulations for the treatment of schizophrenia in routine clinical practice and thereby (3) reduce the number of relapses requiring hospitalisation in patients with schizophrenia under our care. METHOD: Educational initiatives, promotion of reflective practice and patient-specific reminders were used to prompt increased use of LAI antipsychotic medication for patients with schizophrenia. Data relating to the use of these medications and the number of acute admissions for schizophrenia spectrum disorders (F20-29, ICD-10) over time were extracted from existing clinical information systems. RESULTS: Over the 3-year time frame of our local initiative, the use of LAI antipsychotic preparations increased by 11%, the number of acute admissions for schizophrenia/schizoaffective disorder (F20 and F25) decreased by 26% and the number of acute bed days occupied by patients with these diagnoses decreased by 8%. The number of admissions for other psychosis diagnoses (F21-24 and F28-29) did not show the same pattern of improvement. CONCLUSION: In our health care organisation, raising clinicians' awareness of the evidence base relating to the potentially favourable benefit-risk balance for LAI antipsychotic medication compared with oral formulations resulted in more use of the former. There were accompanying reductions in acute admissions and occupied bed days for patients with schizophrenia.

Prescribing clozapine in the UK: Quality improvement issues identified by clinical audit.

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.

Who is prescribed valproate and how carefully is this treatment reviewed in UK mental health services? Data from a clinical audit.

Background: The licensed indications for valproate are narrow, yet this medication is commonly prescribed in mental health services. Objectives: To explore the target symptoms/behaviours for which valproate is prescribed and how well the efficacy and tolerability of this treatment are monitored in routine clinical practice. Design: An audit-based quality improvement (QI) programme in UK mental health services. Methods: Information on valproate prescribing was collected from clinical records using a bespoke data collection tool. Results: Sixty-four NHS mental health Trusts/healthcare organisations submitted data on valproate treatment for 5320 patients. Valproate was clearly prescribed for a licensed indication in 1995 (38%) patients, off-label in 1987 (37%) while the indication was uncertain/not available in 1338 (25%). Of the 919 patients started on valproate treatment within the past year, between a half and two-thirds had each of the relevant baseline physical health checks documented. In 539 (59%) of these patients, valproate was prescribed for an unlicensed indication; the prescription was recognised as off-label in 363 (67%), 20 (6%) of whom were documented as having had this explained to them. Of 631 patients prescribed valproate for between 3 months and a year, early on-treatment assessments of response and side effects were documented in 441 (70%) and 332 (53%), respectively. Of 4401 patients treated for more than a year, annual on-treatment reviews of clinical response and side effects were documented in 2771 (63%) and 2140 (49%), respectively. Conclusion: Our data suggest the majority of prescriptions for valproate in mental health services are not for a licensed indication. Furthermore, patients rarely receive an explanation that their valproate prescription is off-label, perhaps partly because the licensed indications are not widely understood by prescribers. Given the very limited evidence for efficacy for the off-label uses of valproate, failure to routinely conduct early on-treatment and annual reviews of the benefits and side effects of this medication may result in patients remaining on ineffective and poorly tolerated treatment by default.

Prescribing antipsychotic medication for adults with intellectual disability: shared responsibilities between mental health services and primary care.

AIMS AND METHOD: We conducted a secondary analysis of data from a Prescribing Observatory for Mental Health audit to assess the quality of requests from intellectual disability services to primary care for repeat prescriptions of antipsychotic medication. RESULTS: Forty-six National Health Service Trusts submitted treatment data on 977 adults with intellectual disability, receiving antipsychotic medication for more than a year, for whom prescribing responsibility had been transferred to primary care. Therapeutic effects had been monitored in the past 6 months in 80% of cases with a documented communication indicating which service was responsible for this and 72% of those with no such communication. The respective proportions were 69% and 42% for side-effect monitoring, and 79% and 30% for considering reducing/stopping antipsychotic medication. CLINICAL IMPLICATIONS: Where continuing antipsychotic medication is prescribed in primary care for people with intellectual disability, lack of guidance from secondary care regarding responsibilities for monitoring its effectiveness may be associated with inadequate review.

The clinical effectiveness and cost effectiveness of clozapine for inpatients with severe borderline personality disorder (CALMED study): a randomised placebo-controlled trial.

Background: Data from case series suggest that clozapine may benefit inpatients with borderline personality disorder (BPD), but randomised trials have not been conducted. Methods: Multicentre, double-blind, placebo-controlled trial. We aimed to recruit 222 inpatients with severe BPD aged 18 or over, who had failed to respond to other antipsychotic medications. We randomly allocated participants on a 1:1 ratio to receive up to 400 mg of clozapine per day or an inert placebo using a remote web-based randomisation service. The primary outcome was total score on the Zanarini Rating scale for Borderline Personality Disorder (ZAN-BPD) at 6 months. Secondary outcomes included self-harm, aggression, resource use and costs, side effects and adverse events. We used a modified intention to treat analysis (mITT) restricted to those who took one or more dose of trial medication, using a general linear model fitted at 6 months adjusted for baseline score, allocation group and site. Results: The study closed early due to poor recruitment and the impact of the COVID-19 pandemic. Of 29 study participants, 24 (83%) were followed up at 6 months, of whom 21 (72%) were included in the mITT analysis. At 6 months, 11 (73%) participants assigned to clozapine and 6 (43%) of those assigned to placebo were still taking trial medication. Adjusted difference in mean total ZAN-BPD score at 6 months was -3.86 (95% Confidence Intervals = -10.04 to 2.32). There were 14 serious adverse events; 6 in the clozapine arm and 8 in the placebo arm of the trial. There was little difference in the cost of care between groups. Interpretation: We recruited insufficient participants to test the primary hypothesis. The study findings highlight problems in conducting placebo-controlled trials of clozapine and in using clozapine for people with BPD, outside specialist inpatient mental health units. Trial registration: ISRCTN18352058. https://doi.org/10.1186/ISRCTN18352058.

Improving prescribing practice in psychiatry: the experience of the Prescribing Observatory for Mental Health (POMH-UK).

Data from the UK Prescribing Observatory for Mental Health (POMH-UK) suggest that while positive change in prescribing practice can be achieved with focused, audit-based, quality improvement programmes (QIPs) that include feedback of benchmarked performance data and customized change interventions, the time frame for progress is long and improvement generally modest. Improvement may be seen between the baseline audit and re-audit, but supplementary audits conducted in subsequent years can show incremental, sustained improvement in clinical services that have been consistently involved. Audit invariably reveals a marked variation across and within healthcare organizations in the level of compliance with evidence-based clinical practice standards. Additional work has identified various impediments to behavioural change. Some are common to all QIPs, such as the incomplete dissemination of audit results throughout participating organizations and variable uptake of change interventions. Others are specific to particular QIPs, depending on the prescribing issue addressed. For example, in a QIP targeting biochemical monitoring of lithium treatment, the major barrier was the complexity of clinical care arrangements, including multiple interfaces between clinical and laboratory services, which were often not directly or wholly under the control of clinical teams. In this QIP there was little improvement in overall performance against the clinical standards in the total national sample between baseline and re-audit.

Side-effect monitoring of continuing LAI antipsychotic medication in UK adult mental health services.

BACKGROUND: Long-acting injectable (LAI) antipsychotic medications are used to optimise treatment outcomes in schizophrenia. Guaranteed medication delivery increases the responsibility of prescribers to monitor and manage adverse effects. METHODS: In the context of a quality improvement programme conducted by the Prescribing Observatory for Mental Health, a clinical audit addressed documented side-effect monitoring in patients prescribed continuing LAI antipsychotic medication under the care of United Kingdom adult mental health services. RESULTS: A total of 62 mental health services submitted data on 5169 patients prescribed LAI antipsychotic medication for more than a year. An assessment of side effects had been documented in the past year in 2304 (45%) cases. Post hoc analysis showed that extrapyramidal side effects were more likely to have been assessed and found to be present in those patients prescribed LAI haloperidol, flupentixol or zuclopenthixol. There was little other targeting of assessments to the known side effects profiles of individual LAI antipsychotic medications, but when dysphoria had been assessed it was most commonly found with LAI haloperidol treatment and when weight gain, sexual and prolactin-related side effects had been assessed, they were more often identified with LAI paliperidone. CONCLUSION: The data suggest a relatively low frequency of side-effect assessments, largely untargeted. This is likely to result in many adverse effects going unrecognised and unmanaged, thus failing to tackle their potential to confound mental state assessment and adversely affect physical health and adherence. Patients receiving LAI antipsychotic medication have regular contact with a healthcare professional who administers the medication, which provides an opportunity to potentially remedy this situation.

Assessment of adverse effects in clinical studies of antipsychotic medication: survey of methods used.

BACKGROUND: Clinical studies of antipsychotic medication are a primary source of data on the nature of, and relative liability for, adverse effects, relevant to prescribing decisions in clinical practice. AIMS: To identify how safety and tolerability data were collected and reported in recent clinical studies of antipsychotics. METHOD: A survey was conducted of all 167 eligible studies published between 2002 and 2007 on the Cochrane Schizophrenia Group register. RESULTS: Extrapyramidal side-effects (EPS) and weight gain were most frequently assessed. A minority of reports addressed metabolic abnormalities, aversive subjective experiences and sexual dysfunction. Published rating scales were frequently used to evaluate EPS, but systematic methods were rarely applied to other treatment-emergent problems. The definition of individual adverse effects and the manner of reporting were inconsistent. CONCLUSIONS: The way in which safety and tolerability data are collected and reported in clinical studies does not allow for fair and meaningful comparison of the relative risk profiles of individual antipsychotic drugs.

Ethical dilemmas: should antipsychotics ever be prescribed for people with dementia?

The use of antipsychotics for the treatment of behavioural and psychological symptoms of dementia (BPSD) is controversial. Antipsychotics cause harm and evidence-based guidelines advise against their use. We argue that antipsychotics may be justified using a palliative model: by reducing severe distress in those whose life expectancy is short.

Standards of lithium monitoring in mental health Ttrusts in the UK.

BACKGROUND: Lithium is a commonly prescribed drug with a narrow therapeutic index, and recognised adverse effects on the kidneys and thyroid. Clinical guidelines for the management of bipolar affective disorder published by The National Institute for Health and Clinical Excellence (NICE) recommend checks of renal and thyroid function before lithium is prescribed. They further recommend that all patients who are prescribed lithium should have their renal and thyroid function checked every six months, and their serum lithium checked every three months. Adherence to these recommendations has not been subject to national UK audit. METHODS: The Prescribing Observatory for Mental Health (POMH-UK) invited all National Health Service Mental Health Trusts in the UK to participate in a benchmarking audit of lithium monitoring against recommended standards. Data were collected retrospectively from clinical records and submitted electronically. RESULTS: 436 clinical teams from 38 Trusts submitted data for 3,373 patients. In patients recently starting lithium, there was a documented baseline measure of renal or thyroid function in 84% and 82% respectively. For patients prescribed lithium for a year or more, the NICE standards for monitoring lithium serum levels, and renal and thyroid function were met in 30%, 55% and 50% of cases respectively. CONCLUSIONS: The quality of lithium monitoring in patients who are in contact with mental health services falls short of recognised standards and targets. Findings from this audit, along with reports of harm received by the National Patient Safety Agency, prompted a Patient Safety Alert mandating primary care, mental health and acute Trusts, and laboratory staff to work together to ensure systems are in place to support recommended lithium monitoring by December 2010.

Prescribing for moderate or severe unipolar depression in patients under the long-term care of UK adult mental health services.

BACKGROUND: A quality improvement programme addressing prescribing practice for depression was initiated by the Prescribing Observatory for Mental Health. METHODS: A baseline clinical audit against evidence-based practice standards was conducted in UK adult mental health services. RESULTS: A total of 55 mental health services submitted data for 2082 patients, under the care of a community psychiatric team (CMHT) for at least a year, with a diagnosis of moderate or severe unipolar depression, 54% of whom had a comorbid psychiatric diagnosis. Selective serotonin reuptake inhibitors were prescribed for 35% of the patients, other newer generation antidepressants for 60%, tricyclic antidepressants for 6% and monoamine oxidase inhibitors for <1%. The most commonly prescribed individual antidepressants were mirtazapine (33%, usually in combination with another antidepressant), venlafaxine (25%) and sertraline (21%). Patients with severe depression were more likely (p < 0.001) to be co-prescribed an antipsychotic medication, lithium, or to have received electroconvulsive therapy. There was a documented clinical review in the last year in 85%, with a symptom rating scale used in 11%. A documented comprehensive treatment history was accessible for 50% of those prescribed antidepressant medication. CONCLUSION: Patients with moderate or severe depression remaining under the care of a CMHT for longer than a year are clinically complex. The failure to achieve a level of wellness allowing discharge from mental health services may be partly related to the finding that not all patients had the benefit of a systematic approach to clinical assessment and sequential testing of available evidence-based pharmacological interventions.

The physical health and side-effect monitoring of patients prescribed clozapine: data from a clinical audit conducted in UK mental health services.

BACKGROUND: In addition to mandatory haematological monitoring, treatment guidelines recommend routine monitoring of adverse effects and physical health in patients prescribed clozapine. METHODS: NHS trusts/healthcare organisations participated in a clinical audit in the context of a UK quality improvement programme addressing clozapine-prescribing practice. RESULTS: Data relating to 6948 adult patients prescribed clozapine were submitted by 63 NHS trusts/healthcare organisations. Of 481 patients treated with clozapine for up to 18 weeks, there was documented pretreatment screening of blood pressure, heart rate and ECG in at least 90%, and body weight, plasma lipids, plasma glucose/glycated haemoglobin (HbA1c) and physical examination in approximately 80%. During the first 2 weeks of clozapine treatment there was documented daily measurement of both heart rate and blood pressure in 82% and body temperature in 77%. In a subsample of 411 patients, of the 72% who had weekly side-effect assessments documented in the first month of treatment, a structured assessment tool had been used in 29%. Treatment monitoring up to 18 weeks included an ECG in 90%, C-reactive protein (CRP) or creatine kinase in 42%, and troponin or B-type natriuretic peptide (BNP) in 29%. In the 5908 patients prescribed clozapine for at least 1 year, blood pressure and body weight/body mass index were documented in at least 80%, plasma lipids in 78% and plasma glucose in 73%, with an ECG in 55%. Two-thirds were prescribed medication to manage side effects of clozapine and one third of those with a diagnosis of schizophrenia were prescribed a second antipsychotic medication. CONCLUSION: The findings suggest that for most patients treated with clozapine in UK mental health services, physical health screening and side-effect monitoring follow recommended practice, but there was limited use of structured side-effect assessment tools. Monitoring for clozapine-induced myocarditis during the early risk period using markers of inflammation such as CRP, and cardiac damage such as troponin and BNP, was less consistent. This may partly reflect the variation in guideline recommendations for monitoring for myocarditis and partly the selected use of such tests when prompted by cardiac symptoms. The relatively common coprescription of medications for the majority of people on longer-term clozapine treatment may well further increase side-effect burden and physical health risks, reinforcing the need for continuing systematic monitoring.