Title: Research into Antipsychotic Discontinuation and Reduction - long term follow-up
Funder: Department of Health and Social Care

Abstract: Background: Long-term antipsychotic medication is the standard treatment for people with recurrent psychosis or schizophrenia, but the evidence base has serious flaws. In particular, there are no long-term follow-up studies of randomised trials of standard, maintenance antipsychotic treatment compared with gradual discontinuation with this population. Long-term outcomes are particularly important because the condition can last for decades and there is evidence that long-term outcomes may not reflect short-term outcomes. Some evidence suggests that although relapse rates are initially raised among people who reduce or discontinue antipsychotics (possibly due to the effects of withdrawal), they converge with longer duration of follow-up and there may be long-term gains in social functioning. Antipsychotics cause serious physical complications and adverse effects such as sedation and sexual dysfunction that people find debilitating and unpleasant. Many patients and carers want an alternative to long-term antipsychotic treatment, and request to stop it or stop it themselves without support. The Radar trial was designed to evaluate the benefits and risks of a gradual, supported programme of antipsychotic dose reduction and discontinuation compared with continuous (maintenance) antipsychotic treatment in adults with schizophrenia spectrum disorders. The final follow-up of the initial trial is at two years, and after this treatment is determined by patients and clinicians in the usual way. If the 2-year results show beneficial effects of the antipsychotic discontinuation strategy (compared to standard maintenance treatment), it is important to establish whether they are maintained. If they show neutral or negative effects (such as increased relapse), it is important to see whether this pattern changes over time. Research suggests outcomes may diverge from short-term results, with gains manifesting around 3 to 4 years. Radar provides a unique opportunity to evaluate long-term outcomes of maintenance antipsychotic treatment compared with a gradual programme of reduction and discontinuation. Aims and Objectives: The Radar research programme aims to evaluate the effects of a gradual and supported programme of antipsychotic reduction and discontinuation and is the first study of its kind involving people with recurrent psychosis. The current application is for a long-term follow-up to evaluate outcomes 4-7 years after initial enrolment to investigate whether there are differences between people originally allocated to antipsychotic reduction and those allocated to maintenance treatment in social functioning, risk of relapse and other outcomes over the long-term. Research Methods: The Radar trial recruited 253 people and final follow-up takes place at 24 months post-randomisation. The current proposal is to follow participants up from 48 to 84 months post randomisation, depending on when they were randomised. Consent has already been obtained to contact participants. Follow-up assessments will be conducted at the participant s home, clinic or remotely and include measures of social functioning (the primary outcome), quality of life, symptoms, recovery and medication side-effects. Data on relapse, antipsychotic use and service use will be collected from medical records. Statistical analysis will compare randomised groups on all outcomes and an economic analysis will be performed.

Lay abstract: Background to the research Antipsychotics are a type of medication given to people with schizophrenia and similar conditions. Schizophrenia is a serious mental health condition that affects about 1% of the population. It causes psychological symptoms involving a person's thoughts, feelings and behaviour. Antipsychotics can reduce the symptoms of schizophrenia in the short-term, but we do not know if they are always useful when they are used for longer. This is important because most people take antipsychotics for many years. Despite taking antipsychotics many people still find life difficult. Antipsychotics can have unpleasant and dangerous side-effects which can worsen people s quality of life and lead to physical health problems. We have conducted a study that explores what happens to people who reduce or come off their antipsychotic medication gradually with support from their doctor compared with people who stay on antipsychotics. This is called the RADAR (Research into Antipsychotic Discontinuation and Reduction) study. The current proposal is to follow-up people who enrolled in the RADAR study a few years later. Aim(s) of the research We want to understand how people s lives turn out in the long-run if they reduce or stop their antipsychotic medication, with the help of their doctor, compared to if they keep taking it. In order to do this, we want to interview the people enrolled in the RADAR study a few years later to find out how their life has been. This will provide better information for people making choices about their treatment. How would the research be carried out? We enrolled 253 people in the RADAR study at the start. The proposed research will involve conducting a follow-up interview with as many of these people as possible. The interview will take place between 4 and 7 years from the time that people started the RADAR study. In the interview, we will ask people about their ability to live their day to day lives, their symptoms of schizophrenia and about their general health and well-being. Patient and public involvement and engagement (PPIE) The RADAR study has had an active patient and public involvement and engagement (PPIE) group and members of this group reviewed this research proposal. A PPIE member will be part of the management committee that implements and oversees the proposed research. Other people from the PPIE group of the original study will also be consulted. Dissemination We will share the findings with people who take part in the study and also with patients, members of the public and clinicians using newsletters and social media. We will also publish the results in scientific journals and conference presentations.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: MENTAL HEALTH