Pharmacotherapy for Alcohol Craving Reduction: Efficacy of Short-Term Treatments in Alcohol Use Disorder

Background: Alcohol Use Disorder (AUD) is a major contributor to global morbidity, mortality, and socioeconomic burden. Cravings, defined as intense urges to consume alcohol, play a central role in relapse and are recognized as a diagnostic criterion in DSM-5. Pharmacological strategies targeting cravings may offer immediate or short-term relief, complementing existing long-term approaches. However, evidence on short-term (up to approximately three months) anti-craving interventions remains fragmented. Objective: To systematically review randomized, double-blind, placebo-controlled trials (RCTs) assessing the short-term effects of pharmacological treatments on cue-induced alcohol cravings. Methods: A systematic search was conducted in PubMed and PsycINFO using terms related to alcohol, craving, and randomized controlled designs. Eligibility included clinical trials on alcohol-dependent participants that evaluated craving as an outcome. Exclusion criteria encompassed non-clinical studies, non-pharmacological interventions, animal studies, single-blind trials, and studies with psychiatric comorbidities. Study quality was appraised using Cochrane and Joanna Briggs Institute tools. Results: From 442 studies screened, 26 RCTs fulfilled the inclusion criteria. In total, 1097 participants were enrolled across the trials (range = 16–125 per study; mean = 44), predominantly male outpatients aged 15–65 years. Craving was assessed primarily with the Visual Analog Scale and Alcohol Urge Questionnaire. Intervention duration ranged from 1 to 98 days. Naltrexone consistently reduced cue-induced craving across four trials, with additional benefit observed when combined with ondansetron. Varenicline and acamprosate also demonstrated reductions in craving and drinking. Memantine showed efficacy in craving reduction but was not assessed for abstinence. Topiramate was effective, whereas gabapentin showed limited short-term benefit. Other agents (e.g., citalopram, oxytocin, ondansetron, quetiapine) yielded mixed findings, often limited to single studies. Overall, 58% of trials reported positive anti-craving effects, 23% no difference, and 8% increased craving versus placebo. However, these findings should be interpreted in light of important methodological limitations, including small sample sizes and heterogeneous experimental paradigms. Conclusions: This review suggests that naltrexone and varenicline appear to be the most consistently supported short-term pharmacotherapies for alcohol craving within the available evidence, with promising but less consistent findings for memantine, acamprosate, and topiramate. These results highlight potential candidates for immediate craving management in AUD, while underscoring the need for larger and longer-term trials to confirm their efficacy and safety.