title: Ondansetron for reduction of drinking among biologically predisposed alcoholic patients: A randomized controlled trial.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Double-blind, randomized, placebo-controlled clinical trial.
  
  
  METHODS
  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).
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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
authors.affiliation: Department of Psychiatry, University of Texas Health Science Center, 7703 Floyd Curl Dr, Mail Stop 7792, San Antonio, TX 78229-3900, USA. bjohnson@uthscsa.edu
authors.forename: B A
authors.initials: BA
authors.lastname: Johnson
authors.forename: J D
authors.initials: JD
authors.lastname: Roache
authors.forename: M A
authors.initials: MA
authors.lastname: Javors
authors.forename: C C
authors.initials: CC
authors.lastname: DiClemente
authors.forename: C R
authors.initials: CR
authors.lastname: Cloninger
authors.forename: T J
authors.initials: TJ
authors.lastname: Prihoda
authors.forename: P S
authors.initials: PS
authors.lastname: Bordnick
authors.forename: N
authors.initials: N
authors.lastname: Ait-Daoud
authors.forename: J
authors.initials: J
authors.lastname: Hensler
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000097:blood / Q000517:prevention & control*; D000704:Analysis of Variance; D015928:Cognitive Behavioral Therapy; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017294:Ondansetron / Q000008:administration & dosage / Q000627:therapeutic use*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D014168:Transferrin / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D012702:Serotonin Antagonists; D014168:Transferrin; C056759:carbohydrate-deficient transferrin; D017294:Ondansetron