Ondansetron is an effective treatment for patients with early-onset alcoholism, according to researchers in the US. Dr Bankole Johnson (University of Texas Health Science Center, US) and colleagues undertook a randomised, controlled trial in 271 patients with diagnosed alcoholism, comparing the efficacy of ondansetron (1 µg/kg, 4µg/kg or 16µg/kg) with placebo on drinking outcomes (Journal of the American Medical Association 2000;284:963). The study was designed to test the hypothesis that individuals whose alcoholism developed before the age of 25 (early-onset alcoholism) might be responsive to treatment with a selective serotonergic agent. Ondansetron is a 5-HT3 antagonist.
Patients with early-onset and late-onset alcoholism were equally represented in the study. All patients also participated in weekly group cognitive behavioural therapy.
Ondansetron significantly reduced alcohol consumption and increased abstinence among patients with early-onset but not late-onset alcoholism, say the researchers. Drinking outcomes were most markedly improved in "early-onset" patients who received the 4µg/kg dose. These patients had on average 1.56 drinks per day compared with 3.30 drinks in the placebo group. At this dose, ondansetron was superior to placebo in increasing percentage of days abstinent (70.1 compared with 50.2; p=0.02).
Plasma carbohydrate deficient transferrin, a marker of transient alcohol consumption, was measured to confirm the differences in reported alcohol consumption. The researchers hypothesise that "reduced 5-HT neurotransmission in patients with early-onset compared with late-onset alcoholism, differentially upregulates postsynaptic 5-HT3 receptors, a blockade of which may account for ondansetron's differential treatment effectiveness."
In an accompanying editorial (ibid p1016), Dr Henry Kranzler (Alcohol Research Center, Farmington, US) comments: "The study exemplifies a potential role in alcoholism treatment for a medication with a well-defined mechanism of action, reinforcing the rational effort to identify medications to treat the disorder." He adds: "These findings also suggest a potential for the development of pharmacogenetic strategies to treat alcohol dependence."
A spokeswoman for Glaxo Wellcome, the UK manufacturer of Zofran (ondansetron), told The Journal that the company was still assessing data from trials testing ondansetron as a treatment for early-onset alcoholism. A decision on whether to pursue this line of research would be made once all the data had been evaluated.

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