Emerging treatments
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Alcoholmisbruik bij jongerenPublished by: Federaal Wetenschapsbeleid (Belspo)Last published: 2015Alcoholmisbruik bij jongerenPublished by: Federaal Wetenschapsbeleid (Belspo)Last published: 2015Ondansetron
This selective 5-HT3 antagonist has demonstrated some efficacy in terms of outcomes in randomised controlled trials (RCTs) in patients with alcohol use disorder receiving behavioural therapy. In particular, when classifying these patients into early-onset (before age 25) and late-onset alcohol use disorder (after age 25), ondansetron has demonstrated efficacy in patients with early-onset alcohol use disorder.[92][134][135][136][137] Research suggests that ondansetron may be useful in decreasing alcohol consumption and increasing abstinence in patients with a certain genotype (LL) of the 5-HTT gene (LL/LS/SS).[138]
Glucagon-like peptide-1 (GLP-1) receptor agonists
GLP-1 receptor agonists are incretin mimetics with established use in the management of diabetes and obesity. GLP-1 receptors are abundant in brain pathways associated with craving, reward, and dependence pathways, and it is by this mechanism that they may have potential to treat alcohol use disorder. Evidence to-date is, however, predominantly observational. One systematic review of six studies (total 88,190 people) indicated that GLP-1 receptor agonists may reduce alcohol use in some people, though only two studies were placebo-controlled trials (286 participants).[139] One RCT in people with alcohol use disorder found that exenatide had no statistically significant effect on alcohol use, but it did reduce consumption in exploratory analysis of people with body mass index >30 kg/m². The second RCT found that dulaglutide reduced weekly alcohol consumption, though notably this was a subgroup analysis in a trial investigating use for smoking cessation. Observational evidence also indicated an effect on self-reported alcohol use, though studies were overall of low quality.[139] In a subsequent cohort study including 227,866 individuals with alcohol use disorder, use of semaglutide or liraglutide was associated with reduced risk of hospitalisation for the condition over a median 8.8 years follow-up.[140] One later phase 2, placebo-controlled RCT in 48 patients found that low-dose semaglutide affected certain measures of craving and intake (e.g., voluntary consumption in the laboratory scenario and drinks per drinking day) but did not reduce overall drinking days.[141] Gastrointestinal adverse effects are common with GLP-1 receptor agonists.
Baclofen
Baclofen is understood to act upon gamma‐aminobutyric acid type B (GABA[B]) receptors in the brain mesolimbic pathways, hence suppressing dopamine release in response to alcohol. One Cochrane review including 17 RCTs and 1818 people with alcohol use disorder found reliable evidence that baclofen increases percentage abstinent days compared with placebo (mean difference +9.07%, 95% CI 3.30 to 14.85), and likely reduces risk of relapse (RR 0.87, 95% CI 0.77 to 0.99).[142] There was no effect on other outcomes, including number of drinks per drinking day, heavy drinking days, and adverse effects. Only two trials included active drug comparators (naltrexone and acamprosate), providing very uncertain evidence.
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Based on these findings, the World Health Organization (WHO) suggests that baclofen be considered for adults with alcohol use disorder (post initial detoxification).[87] The American College of Gastroenterology also recommends baclofen as an option in patients with comorbid alcohol-related liver disease based on evidence in this population.[43]
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