Combination of Drugs in the Treatment of Alcohol Use Disorder: A Meta-Analysis and Meta-Regression Study

Background: Alcohol Use Disorder (AUD) is highly prevalent among substance use disorders worldwide and is characterized by a multifactorial pathophysiology. AUD treatment is mostly based on combined pharmacotherapy and multidisciplinary clinical approaches. Nonetheless, meta-analytical studies assessing the efficacy of combination therapy are scarcely available. Methods: We searched for randomized clinical trials through PubMed, ClinicalTrials.gov, Cochrane Library, SciELO, Biblioteca Virtual em Saúde, and Google Scholar databases. Original clinical trials published in English and Portuguese were selected. Data collection followed the PRISMA and MOOSE guidelines and was assessed using the Risk of Bias Tool (RoB 2). Heterogeneity was assessed using the Q test. Meta-regression was conducted using Egger's regression method. Twelve articles were finally included in the analysis, and random-effects models were applied on aggregate trial results. Results: The meta-analysis found that combination therapies led to an average 4.045% increase in abstinence rates (95% CI: 0.415% to 7.675%) compared to monotherapies. Meta-regression showed a strong positive association between the use of naltrexone, acamprosate, and sertraline-either alone or in combination-and treatment success in AUD. The meta-regression also highlighted the impact of patients' variables, such as gender, age, country, and psychiatric comorbidities, on their treatment outcomes. These findings may identify a potential therapeutic pathway promoting alcohol abstinence, further supported by a Number Needed to Treat (NNT) of 25, as an acceptable value for substance use disorder treatments. Conclusions: Combined pharmacotherapies are more effective than monotherapy in enhancing abstinence rates in AUD treatment, with naltrexone, acamprosate, and sertraline emerging as key adjunctive agents promoting these outcomes. These findings underscore the complexity of AUD as a multifactorial psychiatric condition and highlight the potential of combined pharmacotherapy as a promising strategy for achieving better treatment outcomes, particularly in terms of abstinence rates.