New research shows that an antinausea medication seems to be effective at reducing alcohol intake in early-onset alcoholics, but not in late-onset alcoholics. Results are fueling theories that the two versions of alcohol dependence are mediated by different mechanisms.

The results of a new study are spurring increased speculation that early-onset and late-onset alcohol dependence operate through different mechanisms. The antinausea medication ondansetron (Zofran) appears to be effective in treating patients with early-onset alcoholism, but shows no effect in those with late-onset alcoholism. Early-onset alcohol dependence appears to be linked to problems with specific serotonin-receptor subtypes.

Early-onset alcoholism, defined as presenting before age 25, is characterized by a more extensive family history of alcoholism, an increased propensity for antisocial behaviors, and a more serious, but stable, disease course than late-onset alcoholism.

Ondansetron has been available in the U.S. since January 1991. Although its mechanism of action as an antinausea agent has not been confirmed, it selectively blocks the 5-HT3 subtype of the serotonin receptor, peripherally as well as in the central nervous system.

The new study was led by Bankole A. Johnson, M.D., Ph.D., the Wurzbach Professor of Psychiatry, department chair for research, and chief of the Division of Alcohol and Drug Addiction at the University of Texas Health Sciences Center, San Antonio. The report appears in the August 23/30 issue of the Journal of the American Medical Association.

"This research is quite consistent with a long list of literature on serotonin dysfunction among early-onset alcoholics," said Enoch Gordis, M.D., director of the National Institute on Alcohol Abuse and Alcoholism, which funded the study.

On the basis of previous studies, it is generally accepted that the combination of drug therapy and some form of psychotherapy is usually the most successful at treating alcoholism. In the current study, investigators compared patients who received one of three different doses of ondansetron or a placebo, all of whom also attended weekly cognitive behavioral psychotherapy sessions. Patients were followed for 11 weeks. Compared with patients who received placebo, all patients with early-onset alcohol dependence receiving ondansetron showed a significant reduction in the average number of drinks they consumed a day, as well as the total number of drinks consumed on each day of drinking. Those patients receiving the middle dosage of the three (4 micrograms per kilogram twice a day) showed the greatest improvement, reporting a significant increase in the percentage of days abstinent from alcohol and total days abstinent per week during the study. The investigators found no significant differences between ondansetron and placebo in patients with late-onset alcohol dependence.

The current research evolved from work published by Johnson and his team in 1993 showing that ondansetron reduced some of alcohol’s subjective positive effects (sense of euphoria, loss of social inhibitions, and so on). The study, however, found positive effects only in early-onset alcoholics.

These differences between early- and late-onset alcohol dependence, the authors suggested, may indicate that the two forms of alcohol dependence are mediated by different biochemical pathways in the brain, with the early-onset form being tied to serotonin dysfunction.