Title: The effectiveness of adjunctive Medication Management and Contingency Management to enhance adherence to medications for relapse prevention in alcohol dependence
Funder: Department of Health and Social Care

Abstract: Design: 3-arm, pragmatic, randomised controlled, parallel group clinical trial of strategies to enhance adherence to acamprosate (AC) for alcohol dependence. Standard support (SS), SS with adjunctive medication management (SS+MM), SS and MM with adjunctive contingency management (SS+MM+CM). Outcome assessment will be at 3, 6 and 12 months post randomisation. Setting: 5 NHS trusts (London (South and North-West), Humberside, Southampton and Birmingham) and community pharmacies. Population: Detoxified alcohol dependent adults, suitable for prescription of AC, willing and able to provide informed consent. Inclusion: Aged >=18, ICD-10 alcohol dependence, completed medically assisted alcohol detoxification, commencing a prescription for AC. Exclusion: Severe physical/mental illness identified by the treating clinicians, current dependence on other substances (except nicotine), participation in another trial, current use of other relapse prevention medication. Heath technologies: MM provided by community pharmacists (weekly for 6 weeks and then fortnightly for 6 weeks and then monthly up to 3 months). MM+CM: Small incentives (vouchers) will be provided to reinforce adherence with MM contingent on attendance at appointment with the community pharmacist. Primary outcome: Percentage of prescribed medication taken estimated using Medication Events Monitoring System (MEMS) and verified using pill count and self-report at 6 months post randomisation. Secondary outcomes: Percentage of prescribed medication taken, estimated by self-report at 12 month follow-up. Alcohol consumption measured by TLFB-90: % days abstinent; units of alcohol per drinking day; time to first drink; relapse to any drinking; and relapse to heavy drinking (8+/6+ UK units (1 unit = 8g alcohol) for males/females on a single occasion). Alcohol related problems (APQ), alcohol craving (AUQ), Participants beliefs about medications (BMQ), the therapeutic relationship with the care giver (STAR), health related quality of life (EQ-5D-5L), Adult Service Use Schedule, costs of control and trial interventions, adverse events. Economic analysis: Analysis of the costs and effects of MM with or without CM for alcohol dependence compared to SS. The primary economic perspective will be the health and social care provider perspective. Broader perspectives will be considered in sensitivity analyses (i.e. criminal justice contacts and criminal activity, productivity losses, patient and family costs). Sample size: Differential allocation of the order of 2:1:1 with twice as many being allocated to the SS group than the intervention groups. A clinically important difference in adherence to medication is estimated as an effect size of the order of 0.3. To estimate this difference using power of 80%, alpha 0.05 with a 2 sided test requires 524 analysed at 6 months across the three groups. Allowing for attrition of 30%, less than observed in other trials in similar populations, requires a total sample size at allocation of 748; 374 allocated to SS, and 187 each to SS+MM and SS+MM+CM. Timetable: Months 0-8: Ethical, R&D, regulatory approvals, adaptation of CM procedure, staff training. Months 9-11 Pilot study. Months 12-33: Recruitment for main trial (average 6 participants/centre each month), Months 12-36: 3 month follow-up, Months 18–42: 6 month follow-up, Months 24–45: 12 month follow-up, Months 46-48: Analysis, report writing, dissemination.

Lay abstract: Alcohol dependence causes considerable physical and mental health problems; the UK has experienced a consistent annual increase in alcohol related hospital admissions, including for alcoholic liver disease. Alcohol costs the UK economy an estimated £21bn per annum, of which the NHS costs are £3.5bn. Providing effective treatment for alcohol dependence and reducing alcohol related hospital admissions has been emphasised as a priority for the UK Government’s Alcohol Strategy. Approximately 4% of the adult population in the UK are affected by alcohol dependence. Currently the main treatment interventions are talking therapies, which are highly effective in people drinking at levels just above the guidelines for ‘safe’ drinking but are less effective in alcohol dependence and relapse is extremely common at around 70% over 12 months post detoxification. The effectiveness of medications in combination with talking therapies for the reduction of alcohol use and relapse in those who are dependent is now well documented. Acamprosate (AC) is recommended as a first line treatment by NICE. AC is thought to stabilise the imbalance between inhibitory (GABA) and excitatory (glutamate) neurotransmitters in the brain. Despite AC’s therapeutic potential, adherence to this medication is low and therefore the maximum benefit that could be gained from taking it is not reached in all patients. Medication management (MM) is an intervention to help improve medication and treatment adherence by providing education, support and advice to service users about their drinking behaviours and medication. This has been used in several clinical trials but is not consistently delivered as part of routine care in specialist alcohol services in the UK. Contingency management (CM), which involves providing small financial or other incentives to change behaviour and/or engage with treatment, including medication adherence, has been found to be effective in substance misusers but there is currently limited evidence available for alcohol dependence. The current study will investigate the effectiveness and cost-effectiveness of MM with or without CM, compared to standard support, for increasing adherence to AC and the subsequent benefits that this will have for alcohol consumption and associated problems. If effective, we believe that MM with CM in addition to standard support has the potential for application across the NHS. Reductions in alcohol consumption, relapse and the associated problems will lessen the burden on the UK economy and the NHS.

Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: MENTAL HEALTH