Title: Managing Adolescent first episode Psychosis: a feasibility Study (MAPS)
Funder: Department of Health and Social Care

Abstract: We aim to assess the feasibility of conducting a definitive trial of interventions for adolescents with first episode psychosis (FEP). We will conduct a 3-arm pilot randomised controlled trial to determine the feasibility of comparing i) antipsychotics (APs) to ii) psychological intervention (PI) and iii) a combined treatment (APs plus PI), in 90 adolescents (aged 14-18) with FEP in NHS services in 4 sites. Randomisation will use randomised-permuted blocks of randomly varying size. Assessors will be masked to allocated treatment. PI consists of Cognitive Behaviour Therapy (CBT) plus family intervention (FI), and allows an individualised approach within clear boundaries, with specific interventions being dependent on an individual formulation (the range of permissible interventions is described in our published manuals (1-3)). Up to 30 sessions of CBT will be delivered over 6 months. FI involves an extra 6 sessions with parents to complement the CBT, improving communication, problem solving and reducing stress. Comparator conditions are APs alone and a combined treatment (APs plus PI). APs will be chosen from those commonly used in the treatment of adolescents and recommended in the recent NICE guidelines, with choice of individual drug made by the managing psychiatrist. Our objectives are to assess feasibility of a definitive trial, including numbers, proportions and characteristics of eligible Adolescents referred by clinicians and adolescents willing to participate, participants who drop out and participants who receive and comply with their allocated intervention. For a definitive trial, our primary hypotheses will be that PI will be non-inferior to APs in effects on psychiatric symptoms, measured using a psychiatric interview (PANSS(4)), and that PI+AP will be superior to either monotherapy. Therapeutic improvement will be assessed in terms of overall symptom severity, but also using broader, clinically relevant outcome measures of social function and target symptoms. Assessors blind to and independent from randomised treatment group allocation will conduct all assessments at baseline, 3, 6 (immediately post the end of treatment) and 12 months (6 months follow-up after the end of treatment). In the event of immediate risk to self or others, or deterioration at 3 months, monotherapy participants will be offered transfer to the AP+PI arm. We will also conduct a nested qualitative interview study with a purposive sub-sample of adolescents (n=15-20), parents (n=15-20) and clinicians (n=15-20) to understand experiences and acceptability of interventions and research procedures, which will further inform a definitive trial. We will also evaluate the suitability of outcome measures to assess effectiveness, safety and acceptability. The 2-year trial will have a recruitment window of 15 months, requiring 1.5 participants per site per month (90 in total). The proposed sample size is adequate for obtaining reliable parameter estimates for sample size estimates for the definitive trial, and demonstrating the feasibility of such a definitive trial. Our team includes expertise in conducting clinical trials of complex interventions, PI for psychosis, psychopharmacology, mental health in adolescents, health economics, nested qualitative research and carer and service user involvement. Five applicants were on the NICE guideline development group for CG155 (5).

Lay abstract: Schizophrenia, a form of psychosis, is amongst the largest challenges for the NHS and is associated with significant personal, social and financial costs. The development of psychosis in childhood has a major detrimental effect on a young person’s personal, social and educational functioning. Common symptoms of psychosis are unusual beliefs (‘delusions’) and hallucinations (most often, hearing voices). The standard medication ('antipsychotics' or ‘APs’) for these problems is often helpful but can have serious side effects. There is mounting evidence that they are poorly tolerated by adolescents, causing significant safety concerns. There is also evidence that having talking therapies (such as ‘cognitive behaviour therapy’ (CBT) or ‘family intervention’) can help reduce symptoms and prevent relapse. The NICE guideline for treatment of psychosis and schizophrenia in adolescents CG155(5) suggests that treatment options should include the possibility of choice between talking therapies, APs or both. However, there is uncertainty around the effectiveness and safety of these interventions in the NHS, with no clear evidence base for adolescents. It is unclear whether it is feasible to conduct a clinical trial to determine the clinical and cost effectiveness of APs in adolescents (aged 14-18) having a first episode of psychosis (FEP). We do not know whether it is possible to recruit adolescents and parents into a randomised controlled trial (RCT), whether they will remain involved in the RCT and whether they will complete the treatment they are allocated to. The structure of mental health services, the relatively rare occurrence of adolescents developing FEP and the strength of preferences for a particular treatment held by doctors, parents and adolescents are all influences that we need to evaluate to determine whether a full RCT is feasible. It is unclear which outcome measures best reflect adolescents, family and clinician views about whether an intervention is successful. We will conduct a small RCT in 4 sites to find out if a larger study could be successfully conducted. The full version will aim to definitively answer questions about which treatments are most effective. We want to test our study methods and see if adolescents find them acceptable. We will do this in a small RCT (a so-called feasibility study) and a qualitative study which will ask people about their experience of taking part in the RCT. We will need around 90 CYP with FEP to take part in this initial study. We will provide roughly a third of participants with talking therapies (both CBT and family intervention), a third with APs and a third with both APs and the talking therapies. Which treatment they get will be randomly determined so that the treatments can be compared in similar groups of people. These findings will help us decide if we should explore this approach further. We have a track record of successful multisite trials of both CBT and APs for schizophrenia and of researching psychosis in CYP (our most recent HTA-funded definitive trial finished recruitment over target). We also have two members of the research team who have been adolescents with psychosis and one member who is a parent of someone who developed schizophrenia when 15 years old. Five of our team were also members of the NICE guideline development group for CG155. We are also conducting the only clinical trial directly comparing talking therapy with APs in adults.

Research activity codes: 6.1 PHARMACEUTICALS;6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MENTAL HEALTH