Ondansetron for reduction of drinking among biologically predisposed alcoholic patients - A randomized controlled trial

Context Early-onset alcoholism differs from late-onset alcoholism by its as sociation with greater serotonergic abnormality and antisocial behaviors. T hus, individuals with early-onset alcoholism may be responsive to treatment with a selective serotonergic agent. Objective To test the hypothesis that drinking outcomes associated with ear ly vs late-onset alcoholism are differentially improved by the selective 5- HT3 (serotonin) antagonist ondansetron. Design Double-blind, randomized, placebo-controlled clinical trial. Settings University of Texas Health Science Center in Houston (April 1995-J une 1998) and University of Texas Health Science Center in San Antonio (Jul y 1998-December 1999). Participants A total of 321 patients with diagnosed alcoholism (mean age, 4 0.6 years; 70.5% male; 78.6% white) were enrolled, 271 of whom proceeded to randomization. Interventions After 1 lead-in week of single-blind placebo, patients were r andomly assigned to receive 11 weeks of treatment with ondansetron, 1 mu g/ kg (n = 67), 4 mu g/kg (n=77), or 16 mu g/kg (n=71) twice per day; or ident ical placebo (n=56). All patients also participated in weekly standardized group cognitive behavioral therapy. Main Outcome Measures Self-reported alcohol consumption (drinks per day, dr inks per drinking day, percentage of days abstinent, and total days abstine nt per study week); and plasma carbohydrate deficient transferrin (CDT) lev el, an objective and sensitive marker of transient alcohol consumption. Results Patients with early-onset alcoholism who received ondansetron (1,4, and 16 mu g/kg twice per day) compared with those who were administered pl acebo, had fewer drinks per day (1.89, 1.56, and 1.87 vs 3.30; P=.03, P=.01 , and P=.02, respectively) and drinks per drinking day (4.75, 4.28, and 5.1 8 vs 6.90; P=.03, P=.004, and P=.03, respectively), Ondansetron, 4 mu g/kg twice per day, was superior to placebo in increasing percentage of days abs tinent (70.10 vs 50.20; P=.02) and total days abstinent per study week (6.7 4 vs 5.92; P=.03). Among patients with early-onset alcoholism, there was a significant difference in the mean log CDT ratio between those who received ondansetron (1 and 4 mu g/kg twice per day) compared with those who receiv ed the placebo (-0.17 and -0.19 vs 0.12; P=.03 and P=.01, respectively). Conclusion Our results suggest that ondansetron (particularly the 4 mu g/kg twice per day dosage) is an effective treatment for patients with early-on set alcoholism, presumably by ameliorating an underlying serotonergic abnor mality.