Luke Worrell

Dear Mr Harris, Regulation 28 Report relating to the death of Luke Alexander Worrell

Thank you for your Regulation 28 report relating to the death of Mr Luke Alexander Worrell which was received on 20th February 2025. I would like to offer my sincere condolences to Mr Worrell’s family on their tragic loss.

I understand from your report that Mr Worrell’s death resulted from ruptured oesophagus, vomiting from ileus and gastro-intestinal upset associated with clozapine treatment. Your report identified the following matters of concern relating to clozapine:

1. There was lack of awareness by a series of clinical staff of the potential fatal side effects of clozapine.

2. There was an inappropriate use of community treatment order, when there was sufficient evidence to keep the patient on a Mental Health Act section.

The Medicines and Healthcare products Regulatory Agency (MHRA) is an executive agency of the Department of Health and Social Care with responsibility for the regulation of medicinal products in the UK. We ensure that medicines are efficacious and acceptably safe, and that information to aid the safe use of a medicine, including possible side effects are appropriately described in the authorised product information. This comprises the Summary of Product Characteristics (SmPC, intended for healthcare professionals), labelling, and Patient Information Leaflet (PIL, provided to patients in each medicine pack). The product information can support discussions between healthcare professionals and patients. The PIL is not intended to replace the discussion with prescribers about the benefits and risks of treatments.

The current special warnings and precautions for use section of the SmPC for clozapine states within the sub-section relating to anticholinergic effects that, “Clozaril has been associated with varying degrees of impairment of intestinal peristalsis, ranging from constipation to intestinal obstruction, faecal impaction, paralytic ileus, megacolon and intestinal infarction ischaemia (see section 4.8). On rare occasions these cases have been fatal. Particular care is necessary in patients who are receiving concomitant medications known to cause constipation (especially those with anticholinergic properties such as some antipsychotics, antidepressants and antiparkinsonian treatments), have a history of colonic disease or a history of lower abdominal surgery as these may exacerbate the situation. It is vital that constipation is recognised and actively treated.”

Gastrointestinal disorders are also described in the undesirable effects section of the SmPC of clozapine, which lists constipation, intestinal obstruction and paralytic ileus as possible adverse reactions to the treatment with clozapine. In addition, the contraindication section states that clozapine is contraindicated in patients with paralytic ileus. Similar messages can be found in the current PIL for clozapine.

In October 2017, we published an article in our bulletin Drug Safety Update which was distributed to healthcare professionals reminding of the potential fatal risks of intestinal obstruction, faecal impaction, and paralytic ileus. This information is also highlighted in the British National Formulary.

We have considered the evidence provided and the circumstances leading to Mr Worrell’s death and acknowledge that your concerns relate to lack of awareness of clinical staff of the potentially fatal side effects of clozapine, and clinical decisions. Unfortunately, we cannot directly address these points, as it is not within our remit to comment on the clinical decisions in specific cases.

We continuously review the safety of medicines on the UK market and take appropriate regulatory action as required. Currently, we are reviewing the product information for clozapine. As part of this review, we will be giving careful consideration to the information which is provided to healthcare professionals, patients and their families and carers, and whether this can be improved to provide greater clarity. We intend to engage with relevant stakeholders during this process to ensure the regulatory documents meet the needs of patients and prescribers. It is anticipated that this review of clozapine will be completed this year, and we will inform you of the outcome.

Should you have any further questions, please do not hesitate to contact my office at Executive.Office@mhra.gov.uk.

Dear Mr Harris,

Thank you for your Regulation 28 report of 21 February 2025 sent to the Secretary of State about the death of Luke Alexander Worrell. I am replying as the Minister with responsibility for patient safety and mental health.

Firstly, I would like to say how saddened I was to read of the circumstances of Mr Worrell’s death, and I offer my sincere condolences to his family and loved ones. The circumstances your report describes are deeply concerning and I am grateful to you for bringing these matters to my attention.

Your report raises concerns over levels of awareness of clinical staff around the potentially fatal side effects of clozapine and the use of a Community Treatment Order (CTO) to support Mr Worrell when there may have been sufficient evidence to detain Mr Worrell under the Mental Health Act.

I note that you have also addressed these matters of concern to NHS England, the Medicines and Healthcare Products Regulatory Agency (MHRA), the Royal College of Psychiatrists, and the Care Quality Commission. I look forward to working together with these bodies where appropriate to avoid a repetition of the tragic events of this case.

I understand your concern that clinical staff administering clozapine need to have a firm understanding of the drug’s potential side effects. I am aware that the Chief Executive of Medicines and Health Care products Regulatory Agency has provided a response to your report, which sets out the protocols it has in place to ensure clinicians are aware of the side effects of clozapine. This includes ensuring that the special warnings and precautions for use section of the Summary of Product Characteristics (SmPC) for clozapine includes information on the medicine’s anticholinergic effects and ensuring that labelling and Patient Information Leaflets accurately reflect the risk of gastrointestinal disorders.

In its response, the MHRA has considered the evidence provided in your report and acknowledges the concerns relating to the level of awareness of clinical staff around the potentially fatal side effects of clozapine. Whilst the MHRA is unable to comment on the specific clinical decisions made in Mr Worrell’s case, the MHRA is currently reviewing the product information for clozapine which will carefully consider the information provided to healthcare professionals, patients and their families and carers and whether this can be improved to provide greater clarity on the side effects of clozapine. The MHRA will engage with stakeholders to ensure the regulatory documents for clozapine meet the needs of both patients and prescribers. I understand this review is expected to be completed this year and that the MHRA will inform you of the outcome.

I am aware that the National Medical Director of NHS England has written to you setting out the additional measures that have been taken to ensure responsible clinicians are aware of the potentially fatal side effects of clozapine. These include ongoing work to raise awareness in the health community around the potential risks of clozapine.

I understand your concerns around whether the use of a CTO was the appropriate course of action for Mr Worrell’s treatment, as opposed to detaining him under the Mental Health Act. Whilst I am unable to comment on the specific decision made by the psychiatrist to place Mr Worrell under a CTO, the CTO should not have been a barrier to providing better support Mr Worrell.

CTOs are a form of supervised community treatment where an individual can be quickly recalled to hospital to be detained and treated. CTOs are intended to maintain ongoing contact with mental health services to provide support and help prevent relapse. In certain circumstances, patients subject to a CTO may be recalled to hospital under the Mental Health Act. Under section 17E of the Act, a patient can be recalled to hospital if they require medical treatment in hospital for their mental disorder and there would be a risk of harm to the health or safety of the patient or to other persons if the patient were not recalled to hospital for that purpose.

I am aware that the National Medical Director has advised that, in cases like Mr Worrell’s, inpatient mental health teams still have the option to use section 17 to recall individuals to hospital. He has also advised that clear guidance is available within the Mental Health Act Code of Practice1 for responsible clinicians to make decisions on guardianship, section 17 leave, and CTOs. This guidance outlines circumstances for clinicians to consider when making decisions on whether a CTO or section 17 leave would be the most suitable course of action for a patient.

This guidance states that section 17 leave is only suitable for short-term absences from inpatient services for a fixed period or purpose. Section 17 may also be suitable in the longer- term (for more than seven consecutive days) where the clinical team wish to see how the individual manages outside of hospital before making a decision to discharge. For patients who are able to live in the community, a CTO should be considered a better option than longer-term leave for the management of their care. Where longer-term leave is considered under section 17 (for more than seven consecutive days), the responsible clinician must first

1 Code of practice: Mental Health Act 1983 - GOV.UK

consider whether the patient should be discharged on a CTO instead. Any decision to authorise section 17 leave for more than seven days on a second occasion should be fully documented, including why a CTO discharge is not appropriate. Through the Mental Health Bill, which is currently making its way through Parliament, we are introducing further professional oversight in decisions regarding the use and operation of CTOs. The community clinician (the approved clinician who is responsible for overseeing the patient’s care as a community patient) will be involved in decision making in addition to the hospital-based responsible clinician. This includes the decision to make a person subject to a CTO, to vary or suspend conditions made under a CTO, to recall to hospital a patient subject to a CTO, to revoke a CTO after a patient has been recalled, and to discharge the patient from the CTO. This will help ensure better join up between inpatient and community clinical teams and make sure that patients subject to a CTO are benefitting from the framework they provide.

I agree with the point your report raises around the importance of involving the patient, family and carers, and clinicians in communities when planning and supporting an individual to be discharged from hospital. Statutory guidance on discharge from mental health inpatient settings 2 should be referred to by responsible clinicians to ensure that decisions on discharge are firmly centred around patients and their chosen carers and that they are actively involved throughout the process with appropriate input from relevant professionals involved in their ongoing care.

I hope this response is helpful. Thank you for bringing these concerns to my attention.

Dear Mr Harris,

Care Quality Commission: Response to Regulation 28 Report to Prevent Future Deaths following the inquest into the death of Mr Luke Alexander Worrell.

Thank you for your Regulation 28 Report to Prevent Future Deaths dated 21 February 2025 about Mr Worrell's death. I am replying on behalf of the Care Quality Commission (CQC).

Firstly, I would like to say how saddened I was to read of the circumstances of Mr Worrell’s death, and I offer my sincere condolences to his family and loved ones. Your report’s circumstances are concerning, and I am grateful to you for raising these matters.

In the Regulation 28 Report to Prevent Future Deaths, the following concerns were raised to the CQC:

1. The lack of awareness by a series of clinical staff of the potential fatal side effects of Clozapine

2. Inappropriate use of community treatment order, when there was sufficient evidence to keep on a MHA section.

In response to the individual points raised:

1. The Care Quality Commission (CQC) recognises the serious concerns arising from the lack of awareness among some clinical staff regarding the potentially fatal side effects of Clozapine. As the regulator of health and social care in Care Quality Commission Citygate Gallowgate Newcastle upon Tyne NE1 4PA Telephone: 03000 616161

England, we are committed to supporting safe, high-quality care for people receiving treatment with Clozapine, both in inpatient settings and in the community.

Clozapine remains an essential treatment for individuals with mental health conditions such as treatment-resistant schizophrenia; however, its use carries significant risks, including agranulocytosis, myocarditis, and gastrointestinal hypomotility, which require stringent monitoring and management. To ensure high standards of care, the assessment of Clozapine use, including through community Clozapine clinics and the monitoring of Clozapine related concerns, is conducted by our mental health inspectors within the CQC integrated assessment and inspection teams. These teams are further supported by our team of specialist medicines inspectors and our mental health senior specialists.

In addition, our medicines inspection team delivers targeted Clozapine training and awareness sessions for our mental health inspectors across our integrated assessment and inspection teams. These are delivered through dedicated face- to-face training sessions and development days to strengthen the knowledge and vigilance of our integrated assessment and inspection teams.

Our dedicated mental health senior specialists support our integrated assessment and inspection teams in monitoring intelligence and assessing providers. This includes evaluating the safe and lawful use of Clozapine.

Furthermore, the CQC medicines inspection team maintains regular engagement with the Health Services Safety Investigation Body (HSSIB), particularly in relation to investigations into Clozapine-related deaths in inpatient settings. Learning from these investigations is incorporated into our regulatory approach, enhancing our understanding of the safe use of Clozapine in inpatient and community settings.

2. The CQC is concerned by instances of the inappropriate use of Community Treatment Orders (CTOs), particularly where there is sufficient clinical and legal justification to maintain a person on a detention under the Mental Health Act (1983). The inappropriate application of CTOs can compromise both the safety of the individual and the effectiveness of their care and treatment.

As the independent regulator of health and social care in England, we expect providers to ensure that all decisions relating to the use of the Mental Health Act, including transitions to CTOs, are based on clear clinical evidence, follow legal frameworks, and prioritise the individual’s rights and wellbeing.

To support this, the CQC has a team of dedicated Mental Health Act Reviewers who work alongside our integrated assessment and inspection teams. These specialists provide expert advice and oversight in assessing the use and application of the Mental Health Act across both inpatient and community mental health services, including the use of CTOs.

During the CQC assessment processes, our reviewers assess whether decisions regarding CTOs are legally compliant, clinically justified, and in the best interests of the person receiving care. They also monitor how well providers involve

individuals, carers, and advocates in the decision-making process, and whether services uphold people’s rights under the Act.

Where we identify inappropriate use of CTOs or concerns about compliance with the Mental Health Act, we can undertake additional monitoring, engagement and regulatory action as necessary to drive improvement and hold providers to account. We aim to ensure that all people receiving care under the Mental Health Act are treated lawfully, safely, and with dignity and respect.

All system partners in the health and social care sector must recognise the potentially fatal side effects of Clozapine. Failure to monitor and manage these risks can lead to avoidable harm or death. Equally, the appropriate use of Community Treatment Orders is critical to ensuring individuals receive necessary treatment while maintaining oversight and safeguarding their rights. Collaborative awareness and accountability across services help provide safe, person-centred care and uphold the standards we are committed to as a sector.

The safety of people using mental health services remains a top priority for the CQC, and we will continue to take action where standards fall short to ensure that providers deliver safe, effective, and person-centred care.

Internally, the CQC incorporates information from incidents, notifications, and Regulation 28 Prevention of Future Deaths reports into its ongoing monitoring and assessment planning. Our internal Specific Incidents Guidance process evaluates whether incidents indicate avoidable harm or breaches of fundamental standards. Where necessary, further enquiries are made, and the CQC may undertake targeted or unannounced inspections. If risks are confirmed, regulatory actions such as requirement notices or enforcement measures may be taken to ensure compliance and drive improvements in care.

The Care Quality Commission’s local integrated assessment and inspection teams actively monitor Oxleas NHS Foundation Trust and Lewisham and Greenwich NHS Trust through continuous engagement and risk-based assessments. This includes gathering intelligence from various sources such as patient feedback, incident reports, and partner organisations. Regular meetings with the trusts and attendance at key committees, like Oxleas’ mortality surveillance committee, allow the CQC to review performance, address concerns, and seek assurance on improved care quality and safety. In addition to this local monitoring, the CQC has committed to a national review of adult community mental health services across England, following the 2024 Section 48 special review of Nottinghamshire Healthcare NHS Foundation Trust. This work includes inspections of services such as community-based mental health services for adults of working age and mental health crisis services and health-based places of safety to identify gaps in care quality, patient and public safety, and staff experience. The review will assess both individual trust services and provide a broader national overview of community mental health service provision.

We are grateful for the information you have shared. It is invaluable in helping us monitor the quality of care provided across services and ensure that providers meet the standards expected under the Health and Social Care Act (2008) and the associated Regulated Activities Regulations (2014). We appreciate the coroner raising these

concerns with us. We will continue to monitor the trusts and any information we receive in line with our internal processes and methodology. If you have any further queries, please do not hesitate to contact us.