Adjunctive Medication Management and Contingency Management to enhance adherence to acamprosate for alcohol dependence: the ADAM trial RCT
Authors: Donoghue Kim , Boniface Sadie , Brobbin Eileen , Byford Sarah , Coleman Rachel , Coulton Simon , Day Edward , Dhital Ranjita , Farid Anum , Hermann Laura , Jordan Amy , Kimergård Andreas , Koutsou Maria-Leoni , Lingford-Hughes Anne , Marsden John , Neale Joanne , O’Neill Aimee , Phillips Thomas , Shearer James , Sinclair Julia , Smith Joanna , Strang John , Weinman John , Whittlesea Cate , Widyaratna Kideshini , Drummond Colin 
Published: November 2023

Background
Acamprosate is an effective and cost-effective medication for alcohol relapse prevention but poor adherence can limit its full benefit. Effective interventions to support adherence to acamprosate are therefore needed.

Objectives
To determine the effectiveness of Medication Management, with and without Contingency Management, compared to Standard Support alone in enhancing adherence to acamprosate and the impact of adherence to acamprosate on abstinence and reduced alcohol consumption.

Design
Multicentre, three-arm, parallel-group, randomised controlled clinical trial.

Setting
Specialist alcohol treatment services in five regions of England (South East London, Central and North West London, Wessex, Yorkshire and Humber and West Midlands).

Participants
Adults (aged 18 years or more), an International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, diagnosis of alcohol dependence, abstinent from alcohol at baseline assessment, in receipt of a prescription for acamprosate.

Interventions
(1) Standard Support, (2) Standard Support with adjunctive Medication Management provided by pharmacists via a clinical contact centre (12 sessions over 6 months), (3) Standard Support with adjunctive Medication Management plus Contingency Management that consisted of vouchers (up to £120) to reinforce participation in Medication Management. Consenting participants were randomised in a 2 : 1 : 1 ratio to one of the three groups using a stratified random permuted block method using a remote system. Participants and researchers were not blind to treatment allocation.

Main outcome measures
Primary outcome: self-reported percentage of medication taken in the previous 28 days at 6 months post randomisation. Economic outcome: EuroQol-5 Dimensions, a five-level version, used to calculate quality-adjusted life-years, with costs estimated using the Adult Service Use Schedule.

Results
Of the 1459 potential participants approached, 1019 (70%) were assessed and 739 (73 consented to participate in the study, 372 (50%) were allocated to Standard Support, 182 (25%) to Standard Support with Medication Management and 185 (25%) to Standard Support and Medication Management with Contingency Management. Data were available for 518 (70%) of participants at 6-month follow-up, 255 (68.5%) allocated to Standard Support, 122 (67.0%) to Standard Support and Medication Management and 141 (76.2%) to Standard Support and Medication Management with Contingency Management. The mean difference of per cent adherence to acamprosate was higher for those who received Standard Support and Medication Management with Contingency Management (10.6%, 95% confidence interval 19.6% to 1.6%) compared to Standard Support alone, at the primary end point (6-month follow-up). There was no significant difference in per cent days adherent when comparing Standard Support and Medication Management with Standard Support alone 3.1% (95% confidence interval 12.8% to −6.5%) or comparing Standard Support and Medication Management with Standard Support and Medication Management with Contingency Management 7.9% (95% confidence interval 18.7% to −2.8%). The primary economic analysis at 6 months found that Standard Support and Medication Management with Contingency Management was cost-effective compared to Standard Support alone, achieving small gains in quality-adjusted life-years at a lower cost per participant. Cost-effectiveness was not observed for adjunctive Medication Management compared to Standard Support alone. There were no serious adverse events related to the trial interventions reported.

Limitations
The trial’s primary outcome measure changed substantially due to data collection difficulties and therefore relied on a measure of self-reported adherence. A lower than anticipated follow-up rate at 12 months may have lowered the statistical power to detect differences in the secondary analyses, although the primary analysis was not impacted.

Conclusions
Medication Management enhanced with Contingency Management is beneficial to patients for supporting them to take acamprosate.

Future work
Given our findings in relation to Contingency Management enhancing Medication Management adherence, future trials should be developed to explore its effectiveness and cost-effectiveness with other alcohol interventions where there is evidence of poor adherence.

Trial registration
This trial is registered as ISRCTN17083622 https://doi.org/10.1186/ISRCTN17083622.

Funding
This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 22. See the NIHR Journals Library website for further project information.