Title: ANti-psychotic Drug REduction in primary care for Adults with Learning Disabilities (ANDREA-LD): A Randomised Double-blind Placebo Controlled Trial
Funder: Division for Social Care and Health Research (Wales)

Abstract: Design: Randomised double-blind placebo-controlled non-inferiority withdrawal trial. Setting: Primary care. Target Population: Adults with learning disabilities (LD) identified through practice LD registers prescribed one of two anti-psychotic drugs haloperidol or risperidone for treatment of challenging behaviour with no known current psychosis or previous recurrence of psychosis following prior drug reduction. Health Technologies Being Assessed: Anti-psychotic medication (typical haloperidol and atypical risperidone) prescribed to adults with LD for treatment of challenging behaviour. The experimental group will proceed through 4 monthly approx. 25% reduction stages within a 6 month period (although blinded the doctor has discretion to delay progression to the next step). The control group will maintain baseline treatment. Drugs will be encapsulated to establish blinding but treatment will remain primary care led. Primary care will be supported by a treatment and safety package including guidance on emerging behavioural movement disorder and psychiatric symptoms Changes to medication may be made in either arm by exiting the trial and removing the blinding. Treatment achieved at 6 months will be maintained for a further 3 months under blind conditions. At 9 months the blinding will be broken for clinicians and patients and medication changes monitored up to 12 months.Measurement of Cost and Outcomes: Drug dosage will be monitored as percent of daily defined dose. Aggression (using the Modified Overt Aggression Scale) has been chosen as primary outcome. The Tyrer et al. (2008) treatment trial proposed that a score difference of 4 was clinically significant. As this is a non-inferiority comparison a score difference of 3 or less will be taken as clinically non-significant. Other challenging behaviour will be assessed using the Aberrant Behavior Checklist a commonly used assessment designed for adults with LD. Mental health will be monitored using the LD specific PASS-ADD Checklist and threshold scores. Adverse events will be assessed by the Udvalg for Kliniske Undersøgelser scale (UKU) and movement disorders by the Dyskinesia Identification System Condensed User Scale (DISCUS). Both have been used in prior research in this area (Ahmed et al. 2000 Tyrer et al. 2008). Cost consequences will include costs of medication professional consultations and hospitalisation/admission to other services due to challenging behaviour or mental ill-health. Costs estimates of medication and health social care and unpaid carer inputs will be recorded using a LD version of the Client Service Receipt Inventory used in a similar study (Romeo et al. 2009).Sample Size: To achieve 90% power with a one-sided alpha=.05 an expected difference=0 a common SD=8 with a non-inferiority margin on the MOAS of 3 a sample of 246 (123 per group) is required. We will recruit 310 to allow for 20% drop-out. Following baseline assessments patients will be randomised to experimental reduction (n=155) or control treatment as usual (n=155). Randomisation will be carried out in advance via a remote automated system and balanced with respect to medication type and dosage. The South East Wales Trials Unit will hold the master copy of randomisation (electronically) and inform the pharmacy of allocation current medication and dose for each participant. Project Timetable (including recruitment rate): Main stages: 6 Mths prior up to the start: Initial Preparation (e.g. ethical/MHRA approval R&D initial HR) Mths 1-6: Preparation for Data Collection & Intervention (e.g. GP support blinded medication) Mths 5-7: Recruitment Pilot Mths 8-20: Continued Recruitment Mths 8-21: Baseline Assessments Mths 8-27: Intervention Mths 17-30: Post-intervention Assessments Mths 18-33: Qualitative Follow-up Study and Final Assessments Mth 33: Completed data collection Mth 36: Completed analysis Mth 39: Completed reporting and dissemination. (Recruitment rate=av 20 per month inc pilot)


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: MENTAL HEALTH