Title: Overcoming persecutory delusions.
Funder: Department of Health and Social Care

Abstract: Background: Persecutory delusions occur in over 70% of patients with schizophrenia. This major psychotic experience is a key treatment target. The delusion has substantial impact for patients (and families), including suicidal ideation, isolation, and hospital admission. Schizophrenia is among the top ten disorders in terms of burden of illness, disability and societal and health costs worldwide. The total annual cost to the public sector in England is over 7 billion. Life expectancy is 15-20 years shorter for people with these problems. Approximately half of patients do not respond adequately to the first line treatment, medication. Residual problems are very common. Examining care provision, the Schizophrenia Commission (2012) concluded: What we found was a broken and demoralised system that does not deliver the quality of treatment that is needed for people to recover. This is clearly unacceptable in England in the 21st century.' The 2014 National Audit of Schizophrenia calls for NHS Trusts to increase access to evidence-based psychological interventions. But trials show that the psychological treatment needs improvement. It leads to recovery in only 10% of medication-resistant delusions. A much more efficacious, easily useable intervention is urgently required.The applicant has developed a rigorously tested theoretical model of persecutory delusions. At the core of the delusion is a belief of being unsafe, developed in the context of genetic and environmental risk, that is maintained by a number of factors including disrupted sleep, worrying, negative beliefs about the self, reasoning biases, and avoidance of others. The delusion diminishes if maintaining factors are successfully reduced and the patient is then enabled to relearn that they are safe. The applicant has been developing brief intervention modules each targeting a maintaining factor. One by one the modules have been successfully evaluated. These modules need to be tested together as a full treatment (16-20 sessions). A case series with 12 patients is already indicating the potential major benefits of the full treatment (The Feeling Safe Programme).Aims: The target is recovery in medication-resistant delusions for 50% of patients. The key question asked is: Does the Feeling Safe Programme lead to greater recovery in persecutory delusions, psychological well-being, and activity levels compared to an attention control condition (befriending)? The second aim is to ready the intervention for widespread NHS implementation.Plan of investigation: The main study is a randomised controlled trial for 150 patients who have persecutory delusions despite previous treatment i.e. the group most at need. Patients will be randomised to the Feeling Safe Programme or an attention control condition (thus controlling for non-specific benefits of contact). Medication prescription will continue as usual. Blind assessments will be conducted at 0, 6 (post treatment), and 12 months. All main analyses will be intention-to-treat. A health economic evaluation is included. The study will be embedded into psychosis services in Oxford Health NHS Foundation Trust, providing a case study for implementation. Qualitative interviews will be carried out with patients, carers, and NHS staff to determine views of the intervention and implementation. The treatment is highly likely to have wider applicability in schizophrenia treatment. Therefore a scoping exercise will be carried out with a cohort of 200 patients with early psychosis in the Thames Valley region.Potential benefits to patients and the NHS: It is anticipated that the research professorship will provide a highly efficacious intervention for one of the key problems of severe mental disorder: persecutory delusions. It will be the world's main psychological treatment package for persecutory delusions. The intervention will be highly manualised, and will demystify delusions, so that mental health professionals are able to incorporate it into routine care. A dissemination package will be produced.

Lay abstract: I'm more busy, doing more, going out more, socialising every day. I feel better and more capable to do stuff.I have more energy, motivation, better mood and I've got hope now, for the future. I have a dream of getting a job running a games shop. And I actually think I could do that now. My friends have noticed a difference too. I'm more confident, worrying less and because of this, the 'scenario [paranoid] thinking' isn't happening every day like it used to. Feeling Safe Programme pilot, Patient 1 Persecutory delusions are a key problem for patients with severe mental disorders such as schizophrenia. Examples include My neighbours are spreading nasty rumours and are tormenting me,MI5, MOSSAD, and the police are trying to get me and torture me, An evil spirit is out to kill me. These strongly held, unfounded beliefs are associated with many negative outcomes, including depression, suicide, disrupted education and employment, isolation, and hospital admission. Life expectancy is substantially reduced. The annual cost to the public sector per patient is 36,000. The main treatment is medication but this is inadequate for many patients. Patients want psychological help for this major problem, but rarely get such help, and standard intervention needs significant improvement. The aim is for a psychological treatment that is as good as those for anxiety disorders and that mental health professionals can feel both competent and enthused to use. There has been a transformation in the understanding of persecutory delusions. Much of this research has been carried out by the applicant and colleagues. It will be used to greatly improve treatment. Fundamental to persecutory delusions are the patients' beliefs that they are unsafe. These feelings of danger (developed in the context of genetic and environmental vulnerability) are maintained by a number of processes (e.g. disrupted sleep, thinking biases, worrying, avoidance of people). The applicant has been carefully developing brief interventions (modules) to target, one by one, each of the key maintaining factors. Once the maintaining factors have been addressed, patients are helped to go back into everyday situations and relearn that they are safe. Hence the delusion reduces. Ten studies by the applicant have evaluated the individual modules, each showing substantial patient benefits. These are now ready to be tested together as a full treatment (16-20 sessions). An initial study with 12 patients is showing the promise of the full intervention. The central aim of the research professorship will be to evaluate the full treatment: The Feeling Safe Programme. The target, supported by the pilot data, is that 50% of patients no longer have persistent persecutory delusions. This will be a remarkable improvement in treatment for patients with medication-resistant delusions, from the current recovery rate of 10% when standard psychological therapy is added. Improvements in levels of psychological well-being and activity are also expected. At the heart of the work will be a rigorous randomised controlled trial. 150 patients with persecutory delusions that have not responded to previous treatment will receive the Feeling Safe Programme or an attention control condition (befriending). (Hence the benefits of the new treatment will be shown to be above time simply talking to a clinician.) Routine care will be unaffected. Patients will be assessed over one year. The second key element to the research addresses the issue of the treatment being provided in services. First, the trial will be embedded into psychosis services in Oxford Health NHS Foundation Trust, providing an implementation case study. Second, patients, carers and NHS staff will be interviewed about the intervention and its implementation, identifying the potential barriers but also ways to facilitate provision. This will be incorporated into a dissemination package. Third, a cohort of 200 patients with early psychosis in the large Thames Valley region will complete clinical assessments related to each module, thus showing the wider applicability of the treatment. The programme of work has been strongly influenced by patient involvement. The focus on treating the psychotic experience (i.e. fears of being unsafe) has been driven by patient concerns. Patients also desire psychological treatment options. Patients have been consulted on the design of the research, as well on the content of intervention materials. There will be a Patient and Public Involvement project group, meeting three times each year, and people with lived experience of psychosis will carry out the patient and carer interviews. The promise is of a major improvement in outcome, using an intervention that patients want and that health professionals have the confidence to use.

Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MENTAL HEALTH