Context: Early-onset alcoholism differs from late-onset alcoholism by its association with greater serotonergic abnormality and antisocial behaviors. Thus, 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 early vs late-onset alcoholism are differentially improved by the selective 5-HT(3) (serotonin) antagonist ondansetron.
Design: Double-blind, randomized, placebo-controlled clinical trial.
Settings: University of Texas Health Science Center in Houston (April 1995-June 1998) and University of Texas Health Science Center in San Antonio (July 1998-December 1999).
Participants: A total of 321 patients with diagnosed alcoholism (mean age, 40.6 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 randomly assigned to receive 11 weeks of treatment with ondansetron, 1 microg/kg (n = 67), 4 microg/kg (n = 77), or 16 microg/kg (n = 71) twice per day; or identical placebo (n = 56). All patients also participated in weekly standardized group cognitive behavioral therapy.
Main outcome measures: Self-reported alcohol consumption (drinks per day, drinks per drinking day, percentage of days abstinent, and total days abstinent per study week); and plasma carbohydrate deficient transferrin (CDT) level, an objective and sensitive marker of transient alcohol consumption.
Results: Patients with early-onset alcoholism who received ondansetron (1, 4, and 16 microg/kg twice per day) compared with those who were administered placebo, 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 5.18 vs 6.90; P =.03, P =.004, and P =.03, respectively). Ondansetron, 4 microg/kg twice per day, was superior to placebo in increasing percentage of days abstinent (70.10 vs 50.20; P =.02) and total days abstinent per study week (6.74 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 microg/kg twice per day) compared with those who received 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 microg/kg twice per day dosage) is an effective treatment for patients with early-onset alcoholism, presumably by ameliorating an underlying serotonergic abnormality. JAMA. 2000;284:963-971