CLEAR: (CLozapine in EARly psychosis) A Multi-Centre, Observational Study of Clozapine for Young People with Treatment Resistant Psychosis in Real World Settings

RESEARCH QUESTION: What is the clinical and cost-effectiveness and patient acceptability of clozapine for children and young people with treatment resistant schizophrenia in real-world settings? BACKGROUND: Clozapine is an antipsychotic drug with unique efficacy. It is the only recommended treatment for treatment-resistant schizophrenia (TRS: failure to respond to at least two different antipsychotic drugs). In addition, it is the most effective of all antipsychotics in reducing hospital use, suicide, aggressive behaviour, violent crime, and substance misuse. However, it is also associated with a range of adverse effects which restrict its use, including blood dyscrasias, for which patients require haematological monitoring. As treatment resistance is increasingly recognised earlier during the course of the illness, the question of whether clozapine should be prescribed in children and young people is increasingly important. However, most research to date has been in older, chronic patients, and both the NICE Guideline Development Group and James Lind Alliance have highlighted the lack of evidence about the efficacy and safety of clozapine in people under age 25. At present, most young patients with schizophrenia who meet criteria for treatment resistance are treated with standard antipsychotics, rather than the clozapine that is recommended by NICE. AIMS AND OBJECTIVES: The trial will assess whether clozapine is more effective than treatment as usual (TAU: standard antipsychotics), at the level of clinical symptoms, patient rated outcomes, quality of life and cost effectiveness. METHODS: This is a multi-centre, open label, blind-rated, observational study of clozapine vs TAU (i.e. compared with other antipsychotics – clinician’s choice) for 12 weeks in 50 children and young people with TRS (<25 years old). We will recruit from NHS-funded secondary care, both inpatient and community settings. The primary outcome is the change in total blind-rated PANSS scores at 12 weeks from baseline. Secondary outcomes, include blind-rated clinical global impression, patient-rated outcomes, quality of life, adverse effects, treatment adherence and service use. TIMELINES FOR DELIVERY: CLEAR's set-up began in Sept 21 as a randomised clinical trial, however due to poor recruitment (randomisation being the biggest barrier) CLEAR was changed to an observational study, where clinicians and patients make their own medication decisions, in June 25. Recruitment will now continue to run for 10 months and study close once the follow up visits are completed. ANTICIPATED IMPACT AND DISSEMINATION: If, as hypothesised, clozapine is shown to be superior to standard antipsychotics, there will be a need to reshape services so that barriers to clozapine treatment in these populations, such as a lack of clozapine clinics in CAMHS services, are addressed. Whatever the results, this study will have important implications for NICE and other guideline producers, policymakers, academics, clinicians, service users and their families and the results will be disseminated to all these groups via the academic literature, continuing professional development, blogs and patient-facing educational materials delivered face to face, in print and online.