Tolerance to baclofen?s sedative effect in alcohol-addicted patients: no dissipation after a period of abstinence

Abstract

To the editor We read with great interest the recent report by Besheer et al. (2004) about the effects of GABAB receptor agonists on parameters of alcohol self-administration in ethanolnaive and self-administering mice. Confirming previous preclinical studies (Colombo et al. 2000, 2002), the authors showed that baclofen was able to decrease alcohol intake in pretreated animals, reducing ethanol-reinforced responding at doses that did not alter water-reinforced responding. Moreover, the authors showed that ethanolexperienced mice were less sensitive to the sedative properties of baclofen than naive mice, suggesting that the combination of baclofen and alcohol or baclofen alone would have less of a negative impact on alcoholic patients than on naive drinker subjects; this observation underlines further the safety of the drug in the treatment of alcohol addiction. However, the authors claim to show evidence for the permanence of cross-tolerance to the agonist after a period of alcohol abstinence, although no data are at present available. Our clinical experience, correctly quoted by the authors (Addolorato et al. 2000, 2002a), are in line with the data by Besheer et al. (2004). Baclofen-treated alcoholic patients showed no serious side effects also in the event of relapse; sleepiness or tiredness but no sedation was found in treated patients (Addolorato et al. 2000, 2002a). These data have been recently replicated by Flannery et al. (2004). Moreover, after the termination of the study period, patients continued our treatment program to prevent relapse and maintain the clinical remission. A number of these patients required a new cycle of baclofen for a sudden craving for alcohol, and the drug was readministered in the same dose as in the study (30 mg/ day refracted in 3 times/day) for 2–4 weeks after a variable period of abstinence (from a minimum of 3 months to a maximum of 14 months). Also in this case, tolerability was fair and no patient showed serious side effects; in particular, no patients reported sedation by the drug and continued their usual daily activities. This observation could indicate that the possible crosstolerance between the sedative effect of ethanol and baclofen persists in alcoholic patients also after periods of abstinence. We think that baclofen represents a promising drug in the clinical treatment of alcoholic patients, also in view of its efficacy to suppress alcohol withdrawal symptoms (Addolorato et al. 2002b, 2003). Therefore, use of baclofen to treat alcohol-dependent patients merits further investigation (NIAAA 2004).