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

Objective: We assessed the effect of N-acetylcysteine, as an adjuvant treatment, on treatment adherence (primary outcome) according to peripheral biomarkers and clinical improvement (secondary outcomes) in patients with alcohol use disorder. Methods: A 9-week randomized, double-blind, placebo-controlled clinical trial was conducted on 53 (n = 25 N-acetylcysteine, n = 28 placebo) inpatients with alcohol use disorder. Neuropeptide Y, oxidative stress and inflammatory biomarkers, and hepatic parameters were analyzed at 3 time points. Results: Seventeen (60.7%) patients in the placebo group and 16 (64%) patients in the Nacetylcysteine group completed the trial. Hepatic biomarker levels changed significantly over time (p < 0.001). Oxidized glutathione levels at admission were lower in the N-acetylcysteine group (p(pairwise) = 0.043). By the end of the study, both groups had similar oxidized glutathione levels (p = 0.868), and oxidized glutathione levels were lower in the placebo group. At the end of the intervention, superoxide dismutase activity had decreased and neuropeptide Y levels had increased in the N-acetylcysteine group. Both groups showed similar mean time to relapse, treatment adherence, and clinical improvement. Conclusions: Our findings reinforce the effects of alcohol on oxidative stress and neuropeptide Y parameters. However, our sample size may limit the generalizability of the results, especially for clinical outcomes. Future randomized clinical trials including patients with less severe alcohol use disorder and longer follow-up may be needed to determine whether N-acetylcysteine could help reduce the mental health burden of this disorder. Clinical Trial Registration: NCT03018236.