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Mental health
Protocol
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)
  1. Joanna Moncrieff1,
  2. Glyn Lewis2,
  3. Nick Freemantle3,
  4. Sonia Johnson2,
  5. Thomas R E Barnes4,
  6. Nicola Morant2,
  7. Vanessa Pinfold5,
  8. Rachael Hunter6,
  9. Lyn J Kent7,
  10. Ruth Smith8,
  11. Katherine Darton9,
  12. Robert Horne10,
  13. Nadia E Crellin2,
  14. Ruth E Cooper11,
  15. Louise Marston6,
  16. Stefan Priebe11
  1. 1Division of Psychiatry, University College London and North East London NHS Foundation Trust, London, UK
  2. 2Division of Psychiatry, University College London, London, UK
  3. 3Institute for Clinical Trials and Methodology, University College London, London, UK
  4. 4Division of Psychiatry, Imperial College London, London, UK
  5. 5McPin Foundation, London, UK
  6. 6Research Department of Primary Care and Population Health, University College London, London, UK
  7. 7Independent consultant, Brentwood, UK
  8. 8Independent consultant, Brighton, UK
  9. 9Independent consultant, London, UK
  10. 10School of Pharmacy, University College London, London, UK
  11. 11Unit for Social and Community Psychiatry, Queen Mary University of London, London, UK
  1. Correspondence to Dr Joanna Moncrieff,Mental Health Sciences, University College London and North East London mental health trust, London, UK; j.moncrieff{at}ucl.ac.uk

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 benefits 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 five-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 identified 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 finish 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.

  • antipsychotics
  • schizophrenia
  • psychosis
  • antipsychotic maintenance, schizophrenia
  • randomised controlled trial
https://creativecommons.org/licenses/by/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

https://doi.org/10.1136/bmjopen-2019-030912

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    Footnotes

    • Contributors JM developed the original concept for the trial and drafted the protocol. All authors contributed to the trial design and methodology. JM, GL, NF, SJ, TB, NM, VP, RH, LK, RS, KD, RH and SP are grantholders. NF provided statistical expertise. NC and RC provided trial management and updated the protocol. JM drafted the manuscript, and JM and NC edited subsequent drafts. All authors reviewed and commented on drafts of the paper and approved the final manuscript version. The study Sponsor has contributed to the study design, data collection, management, analysis and interpretation of data.

    • Funding This research is sponsored by Priment Clinical Trials Unit, University College London (Sponsor’s reference number: 15/0947). This report is independent research funded by the National Institute for Health Research (Programme Grants for Applied Research, Research into Antipsychotic Discontinuation And Reduction (RADAR), RP-PG-0514-20004).

    • Disclaimer The views expressed in this publication are those of the author(s) and not necessarily those of the National Health Service, the National Institute for Health Research (NIHR) or the Department of Health. The NIHR will not have any role during the study execution, analyses or interpretation of data.

    • Competing interests TREB: In the last three years, TREB has been a member of scientific advisory boards for Otsuka/Lundbeck, Newron Pharmaceuticals and Gedeon Richter and received speaker fees from Janssen. GL has acted as an expert witness in cases concerning litigation about antidepressants.

    • Patient consent for publication Not required.

    • Ethics approval London - Brent Research Ethics Committee, 16/LO/1507. Approval letter is uploaded.

    • Provenance and peer review Not commissioned; externally peer reviewed.

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