Background: Recently, we showed by using self-report that combining ondansetron (4 μg/kg twice a day) and naltrexone (25 mg twice a day) was effective at reducing drinking and increasing abstinence among early-onset alcoholics (EOAs), who are characterized by a range of antisocial behaviors and high biological and familial disease predisposition. Here, we investigated whether the self-reported differences in drinking would be corroborated by measurements of serum carbohydrate-deficient transferrin (CDT) level, a sensitive, reliable, and well-validated marker of transient alcohol consumption.

Method: An 8-week double-blind clinical trial was performed in which 20 EOAs were randomized to receive ondansetron (4 μg/kg twice a day) and naltrexone (25 mg twice a day) or placebo as an adjunct to weekly standardized cognitive behavioral therapy. Serum CDT was assessed at weeks 0 (baseline), 4, and 8.

Results: Log serum CDT was significantly lower in the ondansetron and naltrexone group (group mean, 1.44 ± 0.076) compared with the placebo group (group mean, 1.82 ± 0.113), as evidenced by a main effect of group [F (1,15) = 7.2, p= 0.017; effect size = 0.32], visit [F (1,16) = 11.2, p= 0.004; effect size = 0.41], and an interaction between group and visit [F (1,16) = 27.54, p < 0.001; effect size = 0.63].

Conclusions: The combination of ondansetron plus naltrexone was superior to placebo at reducing serum CDT. This corroborated our self-reported drinking data and demonstrated that the medication combination is an effective treatment for EOAs.