Ondansetron for Reduction of Drinking Among Biologically Predisposed Alcoholic Patients

Department of Psychiatry, University of Texas Health Science Center, 7703 Floyd Curl Dr, Mail Stop 7792, San Antonio, TX 78229-3900, USA.
JAMA The Journal of the American Medical Association (Impact Factor: 30.39). 08/2000; 284(8):963-71. DOI: 10.1001/jama.284.8.963
Source: PubMed

ABSTRACT 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.
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.
Double-blind, randomized, placebo-controlled clinical trial.
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).
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.
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.
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.
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).
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

Download full-text


Available from: John Roache, Jul 02, 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A variety of typologies have been used to categorize alcoholism's diverse manifestations. Although the most widely studied typologies are dichotomous ones based on genetic epidemiologic findings or using cluster analytic methods, recent efforts have utilized a single item or the onset of a diagnosis of alcohol dependence to subtype individuals based on the age of alcoholism onset. We compared 3 different methods to subtype alcoholics. This secondary analysis used data from 134 alcohol-dependent participants in a placebo-controlled trial of sertraline (Kranzler et al., 2011). We compared cluster analysis to distinguish 2 risk/severity subtypes (Babor et al., 1992) with 2 age-of-onset subtypes (i.e., based on the age of onset of problem drinking or the age at which alcohol dependence criteria were first met). Each method yielded subgroups that differed significantly from one another on demographic and clinical measures. Although concordance was high between the 2 age-of-onset methods, it was poor between the age-of-onset methods and the cluster analysis-derived approach. All 3 subtyping approaches significantly moderated the effects of sertraline or placebo, but only in the L'L' genotype group, as originally reported (Kranzler et al., 2011). In all cases, sertraline treatment was superior to placebo in later-onset individuals and inferior to placebo in the earlier-onset groups. Because age-of-onset subtypes can be defined retrospectively on an individual basis, they may be more clinically useful than cluster-derived subtypes, which require group data. Because the 2 age-of-onset measures we examined appear to have comparable validity, a single item is easier to use as a measure of the age of onset of problem drinking.
    Alcoholism Clinical and Experimental Research 09/2011; 36(3):509-16. DOI:10.1111/j.1530-0277.2011.01609.x · 3.31 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Substance use disorders are chronic relapsing disorders, leading to significant impairment in psychosocial functioning. Conventional therapies have not been able to alter the outcome of these disorders significantly and frequent relapses continue to occur, despite the development of newer medications, like baclofen, ondansetron, etc. Hence, there is a need to look at complementary and alternate systems of medicine. This article is a review of the evidence for complementary and alternate systems of medicine in substance use disorders. Articles were searched using the Medical Subject Headings (MeSH) database of the PubMed search engine and further non-indexed information was obtained from the Google search engine. The article is organised in parts, each reviewing a different system of medicine in the following order--alternate medical systems, biologically based therapies, energy-based interventions and mind-body interventions; as classified by the National Center for Complementary and Alternative Medicine, National Institutes of Health, USA. The currently available evidence is limited and not very encouraging. At present only acupuncture, herbal therapies and mind-body interventions have shown some positive results in human trials and hold promise for the future. This review emphasises the paucity of research into this important field especially the lack of rigorous human trials. More systematic studies are required before these systems of medicine can be widely recommended in the treatment of substance use disorders.
    Drug and Alcohol Review 05/2009; 28(3):292-300. · 1.55 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This detailed cross-sectional analysis, obtained from a sample of alcohol-dependent patients, attempts to compare multiple methods that have been created to classify or subtype alcoholics. The sample comprised 318 alcohol-dependent patients recruited from the alcoholism unit (NETER) of the Psychiatric Service of Santa Maria University Hospital in Lisbon (Portugal). All subjects were evaluated during the outpatient therapeutical programme for operationalized criteria, reported by each alcoholism typology. Regarding concordance agreement (kappa values) for the three type I/II classifications, von Knorring versus Sullivan yielded the higher rate of agreement, followed by von Knorring versus Gilligan and Gilligan versus Sullivan criteria. Chi-square comparisons showed a significant overlap between Babor type A and Cloninger type I of von Knorring and Sullivan. Over-two-type classifications showed the following significant positive relations: Lesch type I versus NETER heredopathic subtype; Lesch type II versus NETER anxiopathic subtype and Babor type A; Lesch type III versus NETER tymopathic subtype; Lesch type IV versus Cloninger type II of von Knorring and Sullivan criteria; and NETER adictopathic subtype versus Cloninger type II of von Knorring, Sullivan and Gilligan criteria. There is a significant overlap across many of the multivariate alcoholic subtypes purposed, in which much of the concordance is a function of common characteristics in subtype operationalization. Commonalities among these different subtyping classification systems offers the possibility of identifying important dimensions that better differentiate individuals among problem drinker's populations.
    Alcohol and Alcoholism 11/2008; 44(1):46-54. DOI:10.1093/alcalc/agn080 · 2.09 Impact Factor