A randomized, double-blind, placebo-controlled trial of N-acetylcysteine as an adjuvant treatment for alcohol use disorder

Objective: We aimed to assess the effect of N-acetylcysteine (NAC), as an adjuvant treatment, on treatment adherence (primary outcome), in peripheral biomarkers and clinical improvement (secondary outcomes) in alcohol use disorders (AUD) patients.

Methods: A 9-week randomized, double-blind, placebo-controlled trial (RCT) was conducted on 53 (n=25 NAC, n=28 placebo) inpatients with AUD. Neuropeptide Y (NPY), oxidative stress and inflammatory biomarkers, and hepatic parameters were analyzed in three-time moments.

Results: Seventeen (60.7%) subjects in placebo and sixteen (64%) in the NAC group completed the RCT. Levels of hepatic biomarkers significantly changed over time (p<0.001). Oxidized glutathione (GSSG) levels at admission were lower in NAC group ((ppairwise=0.043). By the end of the study, both groups had similar GSSG levels (p=0.868), showing a reduction in GSSG levels in the placebo group. In the NAC group, a decrease in superoxide dismutase (SOD) activity and an increase in NPY levels in the end of the intervention were observed. Both groups showed similar mean survival time to relapse, treatment adherence and clinical improvement.

Conclusion: Our findings reinforce the alcohol effects on oxidative stress and NPY parameters. However, our sample size may limit the generalizability of the results, especially for clinical outcomes. Future RCTs with less severe alcoholics and longer follow-up may be necessary to test if NAC could be helpful to reduce the mental health burden related to AUD.