Adverse effects of oral naltrexone: analysis of data from two clinical trials

Rationale: Naltrexone treatment of alcohol dependence is associated with adverse events that may limit its effectiveness. Consequently, understanding the impact of adverse events on medication compliance and treatment retention may enhance naltrexone therapy of alcoholism. Objectives: To examine the relations among adverse events, drinking behavior, medication compliance and study retention in alcoholics receiving naltrexone for relapse prevention. Methods: The current report is based on analysis of data from 92 subjects who participated in two previously published studies. Moderate or severe adverse effects were monitored weekly and categorized as either neuropsychiatric (NP) or gastrointestinal (GI). Medication compliance was determined by weekly urinary riboflavin testing. Study retention was determined by the proportion of study weeks completed by the subject. The causal relations among adverse events, medication compliance and study retention were analyzed separately for NP and GI adverse events using regression-based recursive path models. Results: Both the NP and GI models fit the data well [NP model: chi (2)(4)=0.59, P=0.96; GI model: chi (2)(4)=2.81, P=0.59]. NP adverse events exerted little influence on medication compliance (beta=-0.17, P=0.071), but directly decreased the length of study retention (beta=-0.35, P<0.001). In contrast, there was a significant impact of GI adverse events on medication compliance (=-0.29, P=0.002), but not directly on study retention (beta=-0.14, P=0.081). Conclusion: Future studies aimed at enhancing the effectiveness of naltrexone should examine ways of reducing both NP and GI adverse events, in order to enhance both medication compliance and treatment retention.