1 Moncrieff J, et al. BMJ Open 2019;9:e030912. doi:10.1136/bmjopen-2019-030912 Open access Randomised controlled trial of gradual antipsychotic reduction and discontinuation in people with schizophrenia and related disorders: the RADAR trial (Research into Antipsychotic Discontinuation and Reduction) Joanna Moncrieff, 1 Glyn Lewis, 2 Nick Freemantle, 3 Sonia Johnson , 2 Thomas R E Barnes, 4 Nicola Morant , 2 Vanessa Pinfold, 5 Rachael Hunter , 6 Lyn J Kent, 7 Ruth Smith, 8 Katherine Darton, 9 Robert Horne, 10 Nadia E Crellin, 2 Ruth E Cooper, 11 Stefan Priebe 11 To cite: Moncrieff J, Lewis G, Freemantle N, et al. Randomised controlled trial of gradual antipsychotic reduction and discontinuation in people with schizophrenia and related disorders: the RADAR trial (Research into Antipsychotic Discontinuation and Reduction). BMJ Open 2019;9:e030912. doi:10.1136/ bmjopen-2019-030912 ► Prepublication history for this paper is available online. To view these fles, please visit the journal online (http://dx.doi. org/10.1136/bmjopen-2019- 030912). Received 08 April 2019 Revised 20 August 2019 Accepted 30 August 2019 For numbered affliations see end of article. Correspondence to Dr Joanna Moncrieff,Mental Health Sciences, University College London and North East London mental health trust, London, UK; j.moncrieff@ucl.ac.uk Protocol © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ. ABSTRACT Introduction Antipsychotic medication is effective in reducing acute symptoms of psychosis, but it has a range of potentially serious and debilitating adverse effects and is often disliked by patients. It is therefore essential it is only used when benefts outweigh harms. Although multiple trials conducted with people with schizophrenia indicate an increased risk of relapse in the short-term following abrupt antipsychotic discontinuation, there is little evidence about the long-term outcome of a gradual process of reduction and discontinuation on social functioning, relapse and other outcomes. Methods and analysis This is a multicentre, randomised controlled trial involving people with schizophrenia and related disorders who have had more than one episode. Participants are randomised to have a clinically-supervised, gradual reduction of antipsychotic medication, leading to discontinuation when possible, or to continue with maintenance treatment. Blinded follow-up assessments are conducted at 6, 12 and 24 months and the primary outcome is social functioning, measured by the Social Functioning Scale at 24 months. A minimum of 134 evaluable participants provides 90% power to detect a fve-point difference, and 206 to detect a four-point difference. Secondary outcomes include severe relapse (admission to hospital) and the study is also intended to detect a minimum 10% difference in severe relapse, which requires 402 participants, assuming a 15% loss to follow-up. Other secondary outcomes include all relapses, as identifed by an independent and blinded endpoint committee, symptoms measured by the Positive and Negative Syndrome Scale, quality of life, adverse effects, self-rated recovery and neuropsychological measures. Enrolment started in 2016. The trial is scheduled to fnish in June 2022. Ethics and dissemination Ethical approval was initially obtained on 27 October 2016 (UK Research Ethics Committee reference 16/LO/1507). Results will be published in peer-reviewed journals and disseminated to the public. Trial registration number ISRCTN90298520. EudraCT: 2016-000709-36. Pre-results. INTRODUCTION Schizophrenia and related conditions affect up to 1% of the population, 1 and are associ- ated with long-term suffering and disability, premature death, physical illness and high costs to individuals and society. 2 Recom- mended treatment for people with recurrent episodes consists of continuing antipsychotic medication. 3 4 Current guidelines do not recommend attempts at reduction or discon- tinuation of antipsychotics after the first episode, and in practice, antipsychotic Strengths and limitations of this study ► The trial will be one of the frst to provide data on the outcome of a gradual process of antipsychotic reduction and discontinuation in people with schizo- phrenia and related disorders. ► The trial will provide relatively long-term outcome data on social functioning as well as relapse and other outcomes. ► There are likely to be some deviations from the planned treatment strategies. ► Longer-term follow-up would be desirable and will be initiated in the future.