Ondansetron With and Without Naltrexone As a Treatment of Biologic Alcoholism: Concepts and Updated Findings

Multiple neurotransmitters in the mesocorticolimbic system that are involved in alcohol's rewarding effects mediate its abuse liability. Abuse liability may be even more pronounced among biologic or early onset alcoholics—characterized by high familial loading and antisocial behaviors—because they may possess abnormalities of serotonin (5-HT) and perhaps μ-opioid function within the mesocorticolimbic system. Therefore, medications such as ondansetron and naltrexone, which target the 5-HT3 and μ-opioid receptor systems, respectively, may each be beneficial for treating early onset alcoholism. Additionally, it would be tempting to hypothesize that the combination of ondansetron and naltrexone may be additive or synergistic in treating early onset alcoholism. The authors' first study showed that ondansetron (1, 4, and 16 μg/kg twice daily) was more efficacious than placebo in treating early onset alcoholism. In a second smaller preliminary study, the authors found that the combination of ondansetron 4 μg/kg twice daily + naltrexone 25 mg twice daily, compared with placebo, appeared to act synergistically at improving the drinking outcomes of early onset alcoholics. That study did not, however, test the independent effects of ondansetron and naltrexone. The authors concluded that while ondansetron is effective at treating early onset alcoholism, its combination with naltrexone might be associated with greater treatment benefits. Further studies testing the factorial combinations of ondansetron and naltrexone are needed to establish synergism, or at least additivity, of effects in treating early onset alcoholism.