Alcohol use disorder (AUD) is a leading cause of morbidity and mortality. 1-2 Alcohol consumption is related to approximately 4% of the global burden of disease. 1 It has been estimated that, in clinical settings and compared to the general population, the relative risk of mortality is 3.38 for male patients and 4.57 for female patients with AUD. 2 Patients who reduce their alcohol consumption may halve this increased risk of mortality compared to patients with AUD who do not. 3 However, currently the approved pharmacotherapies that may help patients with AUD to achieve abstinence and/or reduce alcohol consumption to lower drinking levels are limited in number and efficacy. 4-5 Therefore, there is an urgent need to develop more effective treatments in this area. Preclinical and human studies suggest that baclofen, a GABA B receptor agonist, might be a novel treatment for patients with moderate to severe AUD. 6 Notably, a few years after initial randomized clinical trials (RCTs) were conducted, the potential use of this medication for AUD dramatically increased in its popularity due to a French case report describing the use of very high doses of baclofen to treat alcohol craving and drinking. 7 This intriguing yet purely anecdotical case report led to significant scientific and mass media attention and to the use of baclofen (off-label) in the treatment of AUD, such that the French drugs regulatory agency became involved in evaluating the use of baclofen in AUD. However, clinical studies conducted in Europe, USA, Australia, Israel and that evaluated baclofen efficacy in AUD have yielded conflicting results with some but not all RCTs showing an effect of baclofen. 6 The three recent meta-analyses do not draw definitive conclusions on the efficacy of baclofen in the treatment of AUD. 8-10 In fact, one meta-analysis 8 found no significant superiority of baclofen over placebo on the outcomes of each study whereas the other two found that baclofen treatment significantly increased the rate of abstinent patients 9-10 and time to first lapse 9 compared to placebo. Furthermore, one meta-analysis found larger effect sizes of baclofen among heavy drinkers and studies using lower doses. 9 The other study found no significant efficacy of baclofen in reducing the severity of craving for alcohol, anxiety, and depression. 10 In addition, these two meta-analyses reported no significant efficacy of baclofen on other important outcomes such as rate of abstinence days 9-10 or rate of heavy drinking days. 10 Chiefly, all three meta-analyses found overall a small effect size and substantial heterogeneity among studies. 8-10 Following the publication of these metaanalyses, 8-10 a further RCT has been completed and data analysis is currently under way (JC Garbutt, unpublished; ClinicalTrials.gov: NCT01980706). Despite the lack of consistent evidence of efficacy, baclofen is frequently used off-label to treat AUD, especially in some European countries and Australia. However, there is significant variability in the use of baclofen for cl...

We report for the first time that increased peripheral chemoreflex sensitivity directly decreases sympathetic baroreflex function in CHF patients. This interaction contributes to sympathetic overactivity and blunted sympathetic baroreflex function of CHF patients and may explain how chemoreceptors contribute to the bad prognosis of CHF patients.