Efficacy, tolerability, and safety of low-dose and high-dose baclofen in the treatment of alcohol dependence: A systematic review and meta-analysis

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

“…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, ). However, further evaluation dose–response relationships are an important direction for understanding the implications of higher doses of baclofen and potential subgroups that may derive most benefit (Agabio et al, ).…”

“…Additionally, other dose‐specific psychophysiological baclofen effects have been seen in our study exhibiting high‐dose baclofen effects on attenuation of BOLD response during fMRI alcohol cue reactivity (Logge et al, ). Taken together, psychophysiological indices of baclofen treatment effects may reveal a subset of patients that are more tolerant or derive greater benefits from higher doses, such as heavier drinkers with more severe AUD (Pierce et al, ). This needs to be confirmed by larger psychophysiological studies with patients randomized to treatment, and ideally capturing pre‐treatment baselines (e.g., resting HF‐HRV) to assess any predictive capacity of psychophysiological measures relating to baclofen's prospective effects on drinking outcomes.…”

“…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, 2018). However, further evaluation doseresponse relationships are an important direction for understanding the implications of higher doses of baclofen and potential subgroups that may derive most benefit (Agabio et al, 2018).…”

“…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, 2018).…”

“…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, ).…”