Therapeutic interventions to maintain abstinence from recently detoxified, alcohol dependence in primary care: a systematic review and network meta-analysis
Current NICE guidelines recommend that, for those with moderate to severe alcohol dependence, withdrawal from alcohol is followed by the offer of a combination of either acamprosate or naltrexone and a psychosocial intervention. However, access to these options is often limited, and treatment is relatively resource intensive. In this systematic review and network meta-analysis, we aimed to evaluate interventions that can be delivered in primary care, to determine which are most appropriate for implementation in UK primary care context.
We searched MEDLINE, Embase, PsycINFO, and Cochrane CENTRAL databases for randomised controlled trials (RCTs) from the earliest date to February 2018. Trial registries, ClinicalTrials.gov and the World Health Organization’s International Clinical Trials Registry Platform, were also searched in March 2018 to identify unpublished or ongoing trials. Reference lists of relevant systematic reviews and included studies were also searched to supplement the searches. RCTs were selected if they compared different interventions that could be used in primary care and reported continuous abstinence with at least 12-week follow-ups. The population was alcohol dependent patients who had detoxified recently (within 4 weeks). Abstinence and all-cause dropouts up to 12 months follow up were used to evaluate effectiveness and acceptance of interventions respectively. Two reviewers independently extracted the data and assessed the risk of bias of included studies using the RoB 2 tool. Network meta-analysis was performed to combine results using random effects models. Mean ranks of interventions, along with confidence in the evidence via the Confidence In Network Meta-Analysis (CINeMA) tool, was used to reach conclusions.
A total of 16,555 unique records were retrieved and 62 RCTs (41 interventions) were included. NMA results based on all 62 trials showed that, compared with placebo, acamprosate (OR 1.85, 95% CIs 1.49-2.33), sodium oxybate (OR 2.31, 1.22-4.36), quetiapine (OR 6.75, 1.18-38.05) and topiramate (OR 1.88, 1.06-3.34) were the only interventions associated with an increased probability of abstinence. Based on 60 trials reporting all-cause dropouts, the NMA results indicated potential reductions, compared with placebo, for acamprosate (OR 0.73, 0.62-0.86), naltrexone (OR 0.70, 0.50-0.99), home visits (OR 0.32, 0.11-0.95), topiramate (OR 0.45, 0.24-0.83), acamprosate & nurse follow-ups (OR 0.21, 0.08-0.58) and acamprosate & naltrexone (OR 0.30, 0.13-0.68).
Acamprosate was the only intervention with moderate confidence in the evidence of effectiveness and acceptance in primary care settings. It is uncertain whether other interventions can improve abstinence and reduce dropouts due to low or very low confidence in the evidence. More evidence from high quality RCTs in UK primary care is needed.