Rachel McNamara1, Elizabeth Randell1, David Gillespie1, Fiona Wood2, David Felce3, Renee Romeo4, Lianna Angel1, Aude Espinasse5, Kerry Hood1, Amy Davies6, Andrea Meek1, Katy Addison1, Glyn Jones3, Paul Deslandes7, David Allen8,9, Martin Knapp10, Ajay Thapar3, Michael Kerr3. 1. Centre for Trials Research, Cardiff University, Cardiff, UK. 2. Division of Population Medicine, Cardiff University, Cardiff, UK. 3. Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK. 4. Centre for the Economics of Mental Health, Institute of Psychiatry, King's College London, London, UK. 5. National Institute for Health Research Biomedical Research Centre - Clinical Trials Unit, Royal Marsden Hospital NHS Foundation Trust, Sutton, UK. 6. Community Learning Disability Team, 2gether NHS Foundation Trust, Rotherwas, UK. 7. Faculty of Life Sciences and Education, University of South Wales, Pontypridd, UK. 8. The Tizard Centre, University of Kent, Canterbury, UK. 9. Positive Response Training & Consultancy, Penryn, UK. 10. Personal Social Services Research Unit, London School of Economics, London, UK.
Abstract
BACKGROUND: Data suggest that approximately 50,000 adults with learning disabilities (LDs) in England and Wales are currently prescribed antipsychotic medication. Illness in this population is common, including significant rates of challenging behaviour and mental illness, but there is particular concern over the use of antipsychotics prescribed for reasons other than the treatment of psychosis. Control of challenging behaviour is the primary reason why such medications are prescribed despite the absence of good evidence for any therapeutic effect for this purpose. OBJECTIVES: To assess the feasibility of recruitment and retention and to explore non-efficacy-based barriers to a blinded antipsychotic medication withdrawal programme for adults with LDs without psychosis compared with treatment as usual. A secondary objective was to compare trial arms regarding clinical outcomes. DESIGN: A two-arm individually randomised double-blind placebo-controlled drug reduction trial. SETTING: Recruitment was through community learning disability teams (CLDTs) in south Wales and south-west England. PARTICIPANTS: Adults with LDs who are prescribedrisperidone for treatment of challenging behaviour with no known current psychosis or previous recurrence of psychosis following prior drug reduction. INTERVENTION: A double-blind drug reduction programme leading to full withdrawal within 6 months. Treatment in the intervention group was gradually reduced over a 6-month period and then maintained at the same level for a further 3 months, still under blind conditions. In the control group, the baseline level of medication was maintained throughout the 9-month period. The blind was broken at 9 months, following final data collection. MAIN OUTCOME MEASURES: Feasibility outcomes were (1) the number and proportion of general practices/CLDTs that progressed from initial approach to recruitment of participants and (2) the number and proportion of recruited participants who progressed through the various stages of the study. Trial arms were also compared regarding clinical outcomes, the Modified Overt Aggression Scale, the Aberrant Behaviour Checklist, the Psychiatric Assessment Schedule for Adults with Developmental Disability checklist, the Antipsychotic Side-effect Checklist, the Dyskinesia Identification System Condensed User Scale, the Client Service Receipt Inventory, use of other interventions to manage challenging behaviour, use of as-required (pro re nata) medication and level of psychotropic medication use. RESULTS: Of the 22 participants randomised (intervention, n = 11; control, n = 11), 13 (59%) achieved progression through all four stages of reduction. Follow-up data at 6 and 9 months were obtained for 17 participants (intervention, n = 10; and control, n = 7; 77% of those randomised). There were no clinically important changes in participants' levels of aggression or challenging behaviour at the end of the study. There were no expedited safety reports. Four adverse events and one serious adverse event were reported during the trial. LIMITATIONS: Recruitment was challenging, which was largely a result of difficulty in identifying appropriate persons to consent and carer concerns regarding re-emergence of challenging behaviour. Reduced recruitment meant that the full trial became an exploratory pilot study. CONCLUSIONS: The results indicate that drug reduction is possible and safe. However, concerns about taking part were probably exacerbated by limited availability of alternative (behavioural) interventions to manage behaviour; therefore, focused support and alternative interventions are required. The results of the qualitative study provide important insights into the experiences of people taking part in drug reduction studies that should influence future trial development. FUTURE WORK: We recommend that further work focuses on support for practitioners, carers and patients in reducing antipsychotic medication. TRIAL REGISTRATION: Current Controlled Trials ISRCTN38126962. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 47. See the NIHR Journals Library website for further project information.
RCT Entities:
BACKGROUND: Data suggest that approximately 50,000 adults with learning disabilities (LDs) in England and Wales are currently prescribed antipsychotic medication. Illness in this population is common, including significant rates of challenging behaviour and mental illness, but there is particular concern over the use of antipsychotics prescribed for reasons other than the treatment of psychosis. Control of challenging behaviour is the primary reason why such medications are prescribed despite the absence of good evidence for any therapeutic effect for this purpose. OBJECTIVES: To assess the feasibility of recruitment and retention and to explore non-efficacy-based barriers to a blinded antipsychotic medication withdrawal programme for adults with LDs without psychosis compared with treatment as usual. A secondary objective was to compare trial arms regarding clinical outcomes. DESIGN: A two-arm individually randomised double-blind placebo-controlled drug reduction trial. SETTING: Recruitment was through community learning disability teams (CLDTs) in south Wales and south-west England. PARTICIPANTS: Adults with LDs who are prescribed risperidone for treatment of challenging behaviour with no known current psychosis or previous recurrence of psychosis following prior drug reduction. INTERVENTION: A double-blind drug reduction programme leading to full withdrawal within 6 months. Treatment in the intervention group was gradually reduced over a 6-month period and then maintained at the same level for a further 3 months, still under blind conditions. In the control group, the baseline level of medication was maintained throughout the 9-month period. The blind was broken at 9 months, following final data collection. MAIN OUTCOME MEASURES: Feasibility outcomes were (1) the number and proportion of general practices/CLDTs that progressed from initial approach to recruitment of participants and (2) the number and proportion of recruited participants who progressed through the various stages of the study. Trial arms were also compared regarding clinical outcomes, the Modified Overt Aggression Scale, the Aberrant Behaviour Checklist, the Psychiatric Assessment Schedule for Adults with Developmental Disability checklist, the Antipsychotic Side-effect Checklist, the Dyskinesia Identification System Condensed User Scale, the Client Service Receipt Inventory, use of other interventions to manage challenging behaviour, use of as-required (pro re nata) medication and level of psychotropic medication use. RESULTS: Of the 22 participants randomised (intervention, n = 11; control, n = 11), 13 (59%) achieved progression through all four stages of reduction. Follow-up data at 6 and 9 months were obtained for 17 participants (intervention, n = 10; and control, n = 7; 77% of those randomised). There were no clinically important changes in participants' levels of aggression or challenging behaviour at the end of the study. There were no expedited safety reports. Four adverse events and one serious adverse event were reported during the trial. LIMITATIONS: Recruitment was challenging, which was largely a result of difficulty in identifying appropriate persons to consent and carer concerns regarding re-emergence of challenging behaviour. Reduced recruitment meant that the full trial became an exploratory pilot study. CONCLUSIONS: The results indicate that drug reduction is possible and safe. However, concerns about taking part were probably exacerbated by limited availability of alternative (behavioural) interventions to manage behaviour; therefore, focused support and alternative interventions are required. The results of the qualitative study provide important insights into the experiences of people taking part in drug reduction studies that should influence future trial development. FUTURE WORK: We recommend that further work focuses on support for practitioners, carers and patients in reducing antipsychotic medication. TRIAL REGISTRATION: Current Controlled Trials ISRCTN38126962. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 47. See the NIHR Journals Library website for further project information.
Authors: Angela Henderson; Paula Mcskimming; Deborah Kinnear; Colin McCowan; Alasdair McIntosh; Linda Allan; Sally-Ann Cooper Journal: BMJ Open Date: 2020-09-10 Impact factor: 2.692