Naltrexone-induced nausea in patients treated for alcohol dependence: clinical predictors and evidence for opioid-mediated effects

Naltrexone, an opiate antagonist, is well tolerated by most alcoholic patie nts; however, a subset reports significant nausea that can Limit the effect iveness of this therapy. The goal of this study was to identify risk factor s for naltrexone-precipitated nausea to assist in the development of manage ment strategies to maximize the overall effectiveness of naltrexone. On the basis of the hypothesis that alterations in the endogenous opioid system o ccur with repeated stimulation of endogenous opioids by alcohol, the author s predicted that the recency and intensity of alcohol use would be related to the risk of naltrexone-induced nausea, One hundred twenty alcohol-depend ent subjects participated in an open-label trial of naltrexone, After 5 to 30 days of abstinence, subjects received an initial naltrexone dose of 25 m g followed by a dose of 50 mg daily thereafter for 10 weeks, New-onset adve rse effects were rated mild, moderate, or severe after I week of naltrexone . Logistic regression analyses were used to predict moderate to severe naus ea during the first week of therapy from pretreatment patient characteristi cs. Moderate to severe nausea was reported by 18 subjects (15%) and was Lin ked to poorer medication compliance and heavier drinking during treatment. Risk of nausea was significantly predicted by age, gender, intensity of dri nking, duration of abstinence, and the interaction of abstinence duration a nd intensity of drinking. At shorter durations of abstinence, Lighter drink ers were more Likely to experience nausea than heavier drinkers. However, t he risk of nausea declined with longer periods of abstinence, particularly for lighter drinkers. Younger age and female gender were associated with hi gher rates of nausea. These results support the hypothesis that recency and intensity of alcohol. use are related to opiate antagonist-precipitated na usea and suggest that long-term alcohol use may result in alterations in th e endogenous opioid system, Potential strategies to minimize the risk of na usea in vulnerable individuals are discussed.