Dear Colleagues, In a most interesting development, researchers in Texas have shown significant improvements in drinking behaviour in some alcoholic patients given modest doses of ondansetron (Zofran). This widely used anti-serotonin, anti-nausea drug was given in a 3 month randomised, double-blind, placebo-controlled trial. Compliance was over 90% as measured by history and urine riboflavin tracer. Side effect profile was low with the only significant problem being constipation in 5% of patients. One death occurred in a patient falling down a flight of stairs, unrelated to the treatment (but possibly related to the condition being treated). Patients reported 'drinks per day', 'drinks per drinking day', 'percentage of days abstinent', and 'total days abstinent'. In older onset alcoholics the results were equivocal (n=160). The younger onset group (<25 years, n=161) are believed to comprise those with a stronger genetic component to their alcoholism and appear to have more psychiatric co-morbidity such as antisocial personality traits. In these patients the reductions in alcohol consumed was substantial and significant [those on 4ug/kg twice daily had a dramatic (p<0.001) response compared to placebo. The 'effect sizes' of the benefit of the twice daily medication were up to 0.41 which was in the 'moderate' range. "Patients with early-onset alcoholism who received ondansetron (1, 4, and 16 µg/kg twice daily) 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)."
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Self reported drinking frequencies were corroborated using serum carbohydrate deficient transferrin (CDT). Taken along with blood alcohol concentrations at visits, this makes the study very scientifically rigorous.
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JAMA also contains an enthusiastic editorial by Dr Henry Kranzler from Connecticut ('Medications for Alcohol Dependence. New Vistas'). He waxes about the significance and importance of these findings in the context of disulfiram, naltrexone and acamprosate treatment. In addition, he mentions that SSRI drugs have a positive effect in the older age onset alcoholics, linking the serotonergic basis for much surrounding cravings, reward pathways and other still ill-understood areas.
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This may be a landmark paper. It allows us to match diagnosis with an effective treatment in a way not previously imaginable in alcohol dependency. The findings are consistent with a smaller study (Sellers, Sobell et al. Ontario, 1994) and animal experiments, according to the authors.
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These new findings place an even greater burden on the medical profession to be equal to the 'therapeutic challenge'. Society stands to gain enormously if these research findings can be widely implemented. It is a great tragedy and a travesty that naltrexone uptake has been so slow when it is so very effective in alcoholism, doubling the rates of abstinence. Many physicians still seem to take the line that there is 'nothing you can do for an alcoholic' and 'they have to help themselves'. comments by Andrew Byrne ..
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Johnson BA, Roache JD, Javors MA, DiClemente CC, Cloninger CR, et al. Ondansetron for Reduction of Drinking Among Biologically Predisposed Alcoholic Patients. A Randomized Controlled Trial. JAMA (2000) 284:963-971
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http://jama.ama-assn.org/issues/v284n8/rfull/joc00147.html
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Kranzler H. Medications for Alcohol Dependence. New Vistas. Editorial. JAMA (2000) 284
http://jama.ama-assn.org/issues/v284n8/ffull/jed00057.html
