Mindfulness Therapy for Persecutory Delusions: A definitive randomised controlled trial.

Background Schizophrenia is a severe mental illness with a significant disease, economic and social burden. Persecutory delusions (beliefs that one is about to be harmed or mistreated) are a common symptom of schizophrenia with associated high levels of depression. There are currently no group psychological therapies recommended in NICE guidelines. To address this gap, we conducted an RfPB-funded pilot randomised controlled trial, comparing group mindfulness therapy (GMT) to treatment as usual (TAU) for people with schizophrenia and persecutory delusions (Ellett et al., 2020). In our pilot trial, we found strong evidence of feasibility and acceptability, and it is now timely to progress to conduct a definitive randomised controlled trial (RCT). Aims and Objectives Aim: To assess the effectiveness and cost effectiveness of GMT for people with schizophrenia and persecutory delusions. Objectives: (1) assess the effectiveness of GMT by conducting a definitive RCT comparing GMT+TAU vs TAU; (2) conduct a full health economic evaluation to determine the cost effectiveness of GMT; (3) assess adherence to the therapy protocol; (4) provide the first evaluation of how GMT works and for whom the therapy is most efficacious; (5) provide the first full evaluation of safety indices in a definitive RCT of GMT. Primary hypothesis: Compared with TAU, GMT+TAU will result in a significant reduction in depression immediately after the intervention (4 months post randomisation). Methods A parallel group RCT with single blind assessment comparing GMT + TAU (intervention condition) with TAU alone (control condition). Assessments of primary and secondary outcomes will be carried out at baseline, post therapy (4 months post randomisation) and follow up (8 months post randomisation). Participants will be 144 adults with a schizophrenia spectrum diagnosis with current persecutory delusions, recruited across 2 NHS sites (Southern Health NHS Foundation Trust and Greater Manchester Mental Health NHS Foundation Trust), at least 120 of whom will contribute data to the primary endpoint. The therapy will be delivered according to our published manualised protocol. We will also conduct the first full evaluation of safety indices in a definitive clinical trial, conduct mediation and moderation analyses to understand how, and for whom, the therapy is most efficacious, and assess cost effectiveness. Timelines for delivery The study will be delivered in 30 months. Recruitment will be complete within 18 months. Participants will be recruited in 3 cohorts of 24 (N = 72 per site), and each site will deliver 3 therapy groups. Therapy groups and final assessments will be completed within 25 months, with 5 months allocated for data analysis, dissemination and report/publication writing. Anticipated impact and dissemination If proven effective and cost-effective, GMT will positively impact the lives of people with schizophrenia, by providing the first evidence-based group therapy. This is particularly important as there are no group therapies for schizophrenia in the NICE guidelines. The findings will be disseminated to a range of stakeholders, including service users/carers, academic researchers, clinicians, NHS managers, commissioners and policy makers, research participants and the general public, via conferences, service-user and NHS forums, and public engagement events.