Efficacy and safety of high-dose baclofen for the treatment of alcohol dependence: A multicentre, randomised, double-blind controlled trial

Abstract

Previous randomised placebo-controlled trials with low-to-medium doses of baclofen (30-60mg) showed inconsistent results, but case studies suggested a dose-response effect and positive outcomes in patients on high doses of baclofen (up to 270mg). Its prescription was temporary permitted for the treatment of alcohol dependence (AD) in France, and baclofen is now widely prescribed. Recently, a small RCT found a strong effect of a mean dose of 180mg baclofen. In the present study the efficacy and safety of high doses of baclofen was examined in a multicentre, double-blind, placebo-controlled trial. 151 patients were randomly assigned to either six weeks titration and ten weeks high-dose baclofen (N=58; up to 150mg), low-dose baclofen (N=31; 30mg), or placebo (N=62). The primary outcome measure was time to first relapse. Nine of the 58 patients (15.5%) in the high-dose group reached 150mg and the mean baclofen dose in this group was 93.6mg (SD=40.3). No differences between the survival distributions for the three groups were found in the time to first relapse during the ten-weeks high-dose phase (χ=0.41; p=0.813) or the 16-weeks complete medication period (χ=0.04; p=0.982). There were frequent dose-related adverse events in terms of fatigue, sleepiness, and dry mouth. One medication related serious adverse event occurred in the high-dose baclofen group. Neither low nor high doses of baclofen were effective in the treatment of AD. Adverse events were frequent, although generally mild and transient. Therefore, large-scale prescription of baclofen for the treatment of AD seems premature and should be reconsidered.

Baclofen and naltrexone effects on alcohol self-administration: Comparison of treatment initiated during abstinence or ongoing alcohol access in baboons

“…In three double-blind placebo-controlled clinical trials, alcohol-dependent adults treated with 30–270 mg per day baclofen were more likely to achieve complete abstinence compared to those who received placebo (Addolorato et al, 2002, 2007; Müller et al, 2015). In contrast, four other trials found no significant differences in alcohol abstinence among alcohol-dependent adults given 30–150 mg per day baclofen or placebo (Addolorato et al, 2011; Beraha et al, 2016; Garbutt et al, 2010; Ponizovsky et al, 2015). …”

“…In one study conducted in baboons, acute doses of baclofen (1.8 and 2.4 mg/kg) reduced self-administration responses for alcohol, decreased total alcohol intake, and facilitated extinction of responding directed towards obtaining alcohol (i.e., alcohol seeking; Duke et al, 2014). Randomized studies to date have shown some promise although treatment efficacy has been mixed (Addolorato et al, 2002, 2007, 2011; Beraha et al, 2016; Farokhnia et al, 2017; Garbutt et al, 2010; Girish et al, 2016; Leggio et al, 2015; Lesouef et al, 2014; Müller et al, 2015; Ponizovsky et al, 2015). …”

Brain Functional Magnetic Resonance Imaging Cue-reactivity Can Predict Baclofen Response in Alcohol Use Disorders

“…However, the existing data on its clinical usefulness in humans is equivocal, with three positive8–10) and three negative11–13) randomized controlled trials. Several factors have been examined to explain the inconsistency noted in the response to baclofen.…”

Speaking fluently with baclofen?

“…The benefit of higher doses of baclofen was further demonstrated in a double-blind RCT, where doses up to 270 mg/day (mean 180 mg/day) resulted in significant higher abstinence rates compared with placebo 19. However, in a recent study, we could not replicate this finding,20 but there were three important differences between the studies: our dosage was lower (up to 150 mg), patients received cognitive behavioral therapy (CBT) (not in the study of Müller et al ), and had lower drinking levels before treatment. Due to these contrasting results, further studies have to be awaited to draw final conclusions about the efficacy of baclofen in the treatment of AD.…”

“…In November 2014, the patient decided to participate in a double-blind, placebo-controlled RCT that was conducted to study the efficacy of high doses of baclofen for the treatment of AD (Nederlands Trial Register, number NTR3681; for a detailed description see Beraha et al 20). The patient met all inclusion and none of the exclusion criteria of that study and informed consent were obtained.…”