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Combining Ondansetron and Naltrexone Effectively Treats Biologically Predisposed Alcoholics: From Hypotheses to Preliminary Clinical Evidence
Author(s) -
Johnson Bankole A.,
AitDaoud Nassima,
Prihoda Thomas J.
Publication year - 2000
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2000.tb02048.x
Subject(s) - naltrexone , ondansetron , placebo , alcohol dependence , medicine , opioid antagonist , opioid , antagonist , abstinence , anesthesia , psychology , alcohol , psychiatry , nausea , (+) naloxone , receptor , biochemistry , chemistry , alternative medicine , pathology
Background: Individuals considered to be early onset alcoholics (EOA) are characterized by an early onset age, a broad range of antisocial behaviors, high familial loading, and presumed biological disease predisposition. Ondansetron, a 5‐HT 3 antagonist, improves drinking outcomes and increases abstinence rates among EOA. Individuals with high familial loading for developing alcoholism have lower levels of β‐endorphin and demonstrate a more pronounced increase in β‐endorphin levels in response to alcohol administration compared with individuals who do not have alcoholic relatives. The propensity for naltrexone (a mu opioid antagonist) to reduce alcohol's rewarding effects and drinking in humans is greatest in individuals with high familial loading. Predicated on the added knowledge that 5‐HT 3 receptors may themselves mediate alcohol reward via activation of the endogenous opioid system, we hypothesized that the combination of ondansetron and naltrexone would act synergistically and would be an effective treatment in EOA. Methods: We conducted an 8‐week double‐blind placebo controlled clinical trial in which 20 EOA were randomized to receive ondansetron (4 μg/kg twice a day) + naltrexone (25 mg twice a day) or placebo as an adjunct to weekly standardized group Cognitive Behavioral Therapy. Results: At endpoint, subjects who received ondansetron + naltrexone ( n = 10), compared with those who received placebo ( n = 10), had fewer drinks/day (covariate adjusted mean 0.99 ± 0.60 vs. 3.68 ± 0.63; F 1, 16 = 9.35, p = 0.008; effect size = 1.42), drinks/drinking day (covariate adjusted mean 3.14 ± 0.87 vs. 6.76 ± 0.71; F 1, 13 = 10.45, p = 0.007; effect size = 1.71), and a trend toward increased percent days abstinent (covariate adjusted mean 69.76 ± 8.64 vs. 48.24 ± 9.12; F 1, 16 = 3.58, p = 0.08; effect size = 0.88). Conclusions: Ondansetron plus naltrexone seems to synergistically improve the drinking outcomes of EOA. Larger scale studies that test these medications, both alone and together, among various alcoholic subtypes are needed to establish and extend these promising findings.