Naltrexone and Nalmefene as Modern Psychopharmacotherapy for Alcohol Use Disorder: Modulation of Opioid Receptors and Neurobiological Pathways of Alcohol Action

Background: Alcohol use disorder (AUD) is a grave mental health condition that can result in significant health and social consequences. The medications Naltrexone and Nalmefene are indicated for the treatment of AUD, with Naltrexone having received the most extensive research attention. Methods: The majority of papers assessing universal measures of alcohol consumption employed two primary metrics: total alcohol consumption (TAC) and the number of days per month where individuals engaged in heavy drinking (HDD). Indicators pertaining to the maintenance of complete abstinence were excluded due to the absence of sufficient data. The safety of both substances was also assessed, as were the frequency of side effects and independent patient dropout. The study also incorporated practical factors of the therapy, such as the route of administration, dosage regimen, and the drug’s patient convenience, which can have a significant impact on adherence to therapy. Results: Nalmefene, administered in an “as needed” regimen, demonstrated statistically significant activity in reducing HDD and total alcohol consumption (TAC) among patients with AUD, particularly those with elevated World Health Organization (WHO) DRL risk. Preliminary findings from the ESENSE1 (Efficacy of Nalmefene in Alcohol Dependence; the first phase III study), ESENSE 2 (Efficacy of Nalmefene in Alcohol Dependence, the second phase III study), and SENSE (the final phase III long term-safety and cost-effectiveness study) studies indicate a substantial decrease in HDD and TAC following the initial month of treatment. These effects persist throughout the subsequent follow-up period. Several Japanese studies have corroborated the effectiveness of Nalmefene, demonstrating its efficacy across both short-term and long-term applications. Furthermore, these studies have substantiated its safety profile, indicating that there is no inherent risk of addiction or the emergence of withdrawal symptoms. The mild nature of adverse events (most commonly nausea and dizziness) led to a relatively low discontinuation rate of Nalmefene treatment. A subsequent study, employing a recognized methodology, corroborated the efficacy of psychosocial support in enhancing treatment outcomes. Meta-analyses demonstrate that Naltrexone exhibits comparable efficacy in reducing the frequency and severity of alcohol consumption. In select populations, the injectable form (LAI) of this pharmaceutical agent facilitates less frequent dosing, which is advantageous for the treatment process. A comparison of Nalmefene and Naltrexone reveals that the latter does not demonstrate a significant impact on the likelihood of individuals returning to heavy alcohol consumption. Conclusions: In the treatment of AUD, both naltrexone and nalmefene have been shown to yield positive outcomes, particularly in terms of reducing the HDD and TAC. According to the World Health Organization (WHO) classification, Nalmefene is indicated for individuals with a high risk of developing serious conditions. It has been demonstrated to produce rapid and sustained results while exhibiting a favorable safety profile, characterized by the absence of significant adverse effects. Naltrexone is a medication that has proven to be effective. LAI may have a positive impact on the efficacy of treatment.