Baclofen in the Treatment of Patients With Alcohol Use Disorder and Other Mental Health Disorders

Abstract

A limited number of medications are approved to treat Alcohol Use Disorder (AUD). Furthermore, the magnitude of their therapeutic effect is relatively modest, suggesting the potential for subtypes of patients who respond to a specific medication. The use of these medications is also limited in clinical practice by a series of contraindications such as medical comorbidities and/or concurrent use of other medications. In recent years, animal and human studies have been conducted to evaluate the efficacy of baclofen, a GABAB receptor agonist approved for clinical use as a muscle relaxant, in the treatment of AUD. However, these studies have yielded contrasting results. Despite this discrepancy, baclofen is often used off-label to treat AUD, especially in some European countries and Australia. Recently, several factors have been considered to try to shed light on the potential reasons and mechanisms underlying the inconsistent results obtained until now. The presence of a psychiatric comorbidity may be amongst the abovementioned factors playing a role in explaining different responses to baclofen treatment in terms of alcohol drinking outcomes. Therefore, the aim here was to conduct a narrative review of the scientific literature related to the use of baclofen in AUD, both in patients with and without concomitant psychiatric disorders. All clinical studies (randomized and controlled, open-label, retrospective, human laboratory studies, and case reports) were analyzed and discussed, bearing in mind other potential factors that may have influenced baclofen response, including dose administered, severity of AUD, use of other psychosocial therapies, and the presence of physical disorders. This review indicates that the most frequent psychiatric comorbidities in patients affected by AUD undergoing baclofen treatment are anxiety and mood disorders. Unfortunately, no definitive conclusions can be drawn due to the lack of specific analyses on whether baclofen efficacy is different in AUD patients with comorbid psychiatric disorders vs. those without. Therefore, it will be critical that psychiatric comorbidities are considered in the planning of future studies and in the analysis of the data, with the ultimate goal of understanding whether subtypes of AUD patients may respond best to baclofen.

Is R(+)‐Baclofen the best option for the future of Baclofen in alcohol dependence pharmacotherapy? Insights from the preclinical side

“…Market authorization of RS(±)‐Baclofen has been decided in France by the National Agency for the Safety of Medicines (ANSM) in October 2018 with the maximum dose requirement of 80 mg per day and use after failure of other treatments. However, the international debate about its benefit/risk balance is still open as well as some questions about the great variability in the clinical response and the lack of a dose response 50 . Further studies are thus required in order to better understand the reason of the observed variability 16 …”

Efficacy of pharmacotherapeutics for patients comorbid with alcohol use disorders and depressive symptoms—A bayesian network meta‐analysis

“…Meta‐analysis performed by Foulds et al 101 involved 11 studies concluded that the pooled effect size of change scores of depression scales was significant (SMD 0.25, 0.06‐0.44) only among studies concerned independent depression and was insignificant across all studies. A more recent meta‐analysis 102 included 14 studies indicated that antidepressants were significantly better than placebo on reducing the endpoint scores of interviewer‐rated depression scales (SMD −0.27, −0.49 to −0.04). Our findings were consistent with the latter one and also indicated that non‐antidepressants revealed no benefit to depressive symptoms.…”

Recent Advances in the Potential of Positive Allosteric Modulators of the GABAB Receptor to Treat Alcohol Use Disorder

“…First, contrary to the preclinical data, the clinical literature is overall conflicting, as evidenced by meta-analysis and systemic reviews aimed at examining the efficacy of baclofen for AUD treatment. These have yielded mixed results, but they were completed before these two recent RCTs ( Leggio et al ., 2010 ; Agabio and Leggio, 2018 ; Minozzi et al ., 2018 ; Palpacuer et al ., 2018 ). Consequently, in 2018, a panel of international experts met in Cagliari and reached a consensus statement that concluded that, ‘baclofen remains a promising pharmacotherapy for AUD, however, baclofen’s superiority versus placebo has not been established’.…”