Comment on: “Management of Alcohol Dependence in Patients With Liver Disease”

Abstract

Addolorato et al. [1] recently published a welcome review article in CNS Drugs, entitled ‘‘Management of alcohol dependence in patients with liver disease’’. Alcoholic liver disease (ALD) is too often forgotten within the numerous review articles that are regularly published on alcoholdependence medications, whereas cirrhosis is one of the most dramatic consequences of alcohol dependence and can deeply affect the safe use of numerous medications. Addolorato and colleagues [2] state that the gamma amino-butyric acid type B (GABAB) receptor agonist baclofen should be currently preferred in ALD because baclofen was the sole drug that had a good efficacy/safety profile in ALD patients with alcohol dependence in a study whose results were published in The Lancet. Albeit relevant, this conclusion is relatively ironic in the sense that an off-label treatment for alcohol dependence has exhibited higher evidence in ALD than any of the currently approved medications. This indicates to what extent this field of research has been neglected until now. Although baclofen is definitely one of the most promising drugs for treating alcohol dependence in ALD patients, several important safety concerns remain in using this drug in ALD. The findings of the study in The Lancet were obtained from patients with no psychiatric history and who had undergone permanent monitoring by close relatives throughout the trial period. Moreover, as baclofen was particularly effective in maintaining abstinence, only nine patients within the baclofen group experienced relapse, and the amounts of alcohol drinking were not detailed. Thus, possible interactions between baclofen and alcohol intoxication were difficult to identify. Additionally, no patient presented with hepatic encephalopathy, although this condition has been hypothesized to result from GABArelated mechanisms [3]. For all of these reasons, despite the important advances provided by this study, several safety concerns still persist for baclofen because the patient profiles and monitoring conditions in this study were not comparable to those of real-life patients, in whom significant psychiatric co-morbidities; persisting or recurrent alcohol abuse; or ALD complications, such as encephalopathy, may be found. We believe that the question of dose is even more crucial. In the aforementioned study, baclofen was tested at 30 mg/day. Addolorato’s Roman team has published many articles using this dose, which has thus made the dose the most studied and most supported by evidence in the offlabel use of baclofen for abstinence maintenance. However, a dose–response effect of baclofen has been suspected in alcohol dependence [4], and this drug has recently been used in clinical practice at very high doses, i.e., up to 300 mg/day or more, and notably more with a purpose of temperance than of abstinence [5–8]. Although several of these uses have been limited to last-resort situations by hospital teams that could provide enhanced patient monitoring [9, 10], there also exists certain spreading, albeit less visible, practices of prescribing of high-dose baclofen, notably in France [10]. The possible hepatic toxicity of B. Rolland (&) A. Louvet O. Cottencin R. Bordet University of Lille Nord de France, 59045, Lille, France e-mail: benjrolland@gmail.com; benjamin.rolland@chrulille.fr