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Ondansetron for Reduction of Drinking Among Biologically Predisposed Alcoholic Patients
A Randomized Controlled Trial
Bankole A. Johnson, MD, PhD;
John D. Roache, PhD;
Martin A. Javors, PhD;
Carlo C. DiClemente, PhD;
Claude Robert Cloninger, MD;
Thomas J. Prihoda, PhD;
Patrick S. Bordnick, PhD;
Nassima Ait-Daoud, MD;
Julie Hensler, PhD
JAMA. 2000;284:963-971.
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-HT3 (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 µg/kg (n = 67), 4 µg/kg (n = 77), or 16 µg/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 µg/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 µg/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 µg/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 µg/kg twice per day dosage) is an effective treatment for patients with early-onset alcoholism, presumably by ameliorating an underlying serotonergic abnormality.
Author Affiliations: Department of Psychiatry, University of Texas Health Science Center, San Antonio (Drs Johnson, Roache, Javors, Prihoda, Bordnick, Ait-Daoud, and Hensler); Department of Psychology, University of Maryland, Baltimore (Dr DiClemente); and School of Medicine, Washington University, St Louis, Mo (Dr Cloninger).
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