Pharmacologically controlled drinking in the treatment of alcohol dependence or alcohol use disorders: a systematic review with direct and network meta-analyses on nalmefene, naltrexone, acamprosate, baclofen and topiramate

摘要: Background and aims - Pharmacologically controlled drinking in the treatment of alcohol dependence or use disorders (AUDs) is an emerging concept. Our objective was to explore comparative effectiveness drugs used this indication. Design Systematic review with direct network meta-analysis double-blind randomized trials (RCTs) assessing efficacy nalmefene, naltrexone, acamprosate, baclofen topiramate non-abstinent adults diagnosed AUDs. Two independent reviewers selected published unpublished studies on Medline, Cochrane Library, Embase, ClinicalTrials.gov, contacted pharmaceutical companies, European Medicines Agency Food Drug Administration, extracted data. Setting Thirty-two RCTs. Participants A total 6036 patients. Measurements The primary outcome consumption (TAC). Other outcomes health were considered as secondary outcomes. Findings No study provided comparisons between drugs. risk incomplete data identified 26 (81%) selective reporting 17 (53%). Nalmefene [standardized mean difference (SMD) = -0.19, 95% confidence interval (CI) = -0.29, -0.10; I  = 0%], (SMD = -1.00, CI = -1.80, -0.19; one study) (SMD = -0.77, CI = -1.12, -0.42;  = 0%) showed superiority over placebo TAC. observed for naltrexone acamprosate. Similar results other outcomes, except (the favourable TAC not reproduced). number withdrawals safety reasons increased under nalmefene naltrexone. demonstrated any harm reduction (no powered outcomes). Indirect suggested that superior acamprosate but its profile known be poor. Conclusions There currently no high-grade evidence pharmacological control using patients disorder. Some treatments show low medium reducing across a range high bias. None demonstrates benefit