Baclofen in the treatment of alcohol dependence with or without liver disease: multisite, randomised, double-blind, placebo-controlled trial

Abstract

Baclofen may be an effective treatment option for patients with ALD. However, given the profile of adverse events, the role for this medication might be best limited to specialist services.Declaration of interestNone.

Baclofen modulates cardiovascular responses to appetitive cues in treatment‐seeking alcohol use disorder individuals

“…While reduced resting vagal activity (i.e., HF‐HRV levels) is usually associated with less adaptability to situational demands (Laborde et al, ; Thayer et al, ), in this study high‐dose baclofen participants with lower resting vagal activity (shown through lower HF‐HRV) intriguingly demonstrated better drinking outcomes through reduced risky drinking. One potential explanation is that baclofen may have sedating effects (Leggio et al, ), particularly in higher doses when combined with alcohol (Evans & Bisaga, ; Morley et al, ). Considering a substantial proportion of the current study participants (around 70%) were still consuming alcohol during the treatment trial, baclofen and alcohol in combination may have reduced daily consumption for some high‐dose baclofen participants.…”

“…These dose‐specific associations between cue‐related HF‐HRV activity and prospective drinking outcomes suggest dose‐specific effects that have not yet been evidenced in clinical outcomes of baclofen RCTs. This includes the primary outcomes of this study's parent trial (Morley et al, ) and other randomized controlled studies, which do not demonstrate a higher dose‐specific response on reducing drinking outcomes (Beraha et al, ; Reynaud et al, ). Higher doses of baclofen (>60 mg/day) are not considered more efficacious in reducing alcohol consumption outcomes than lower doses, and patients generally demonstrate lower tolerability with higher doses (Pierce et al, ).…”

“…If eligible, participants were then scheduled for the enrolment assessment (see below) within 1 week. Consenting participants meeting inclusion criteria were randomized for an out‐patient pharmacotherapy double‐blind RCT (Morley et al, ) to receive placebo, or low‐dose (30 mg/day) or high‐dose (75 mg/day) baclofen for 12 weeks (for medication titration schedule see Figure ). At approximately the second week of the trial (on average 11 days, range: 7–15 days) participants completed the psychophysiological cue reactivity task.…”

“…All participants included in this cue reactivity substudy provided written informed consent after commencement of randomization for the main trial. The clinical protocol (Morley, Leung, Baillie, & Haber, ) and primary trial outcomes have been published elsewhere (Morley et al, ). The study was approved by the Human Ethics Review Committee of the Sydney Local Health District (X11‐0154).…”

“…Baclofen, a GABA B agonist has recently emerged as a potential pharmacotherapy for AUD (Agabio et al, ). Results from randomized controlled trials (RCTs) of baclofen in alcohol dependent participants have been mixed, with some positive studies reported (Addolorato et al, ; Addolorato et al, ; Morley et al, ; Müller et al, ) while several other studies failed to demonstrate any significant effect (Garbutt, Kampov‐Polevoy, Gallop, Kalka‐Juhl, & Flannery, ; Morley et al, ) even when high doses of baclofen (up to 180 mg/day) were used (Beraha et al, ; Reynaud et al, ). Meta‐analyses conclude that baclofen seems to be an effective treatment for AUD whereby high doses (>60 mg) were not more effective than low doses of baclofen (30–60 mg) although this may be explained by low tolerability (Pierce, Sutterland, Beraha, Morley, & van den Brink, ).…”