Novel Agents for the Pharmacological Treatment of Alcohol Use Disorder

Abstract

Alcohol use disorder (AUD) is a highly prevalent but severely under-treated disorder, with only three widely-approved pharmacotherapies. Given that AUD is a very heterogeneous disorder, it is unlikely that one single medication will be effective for all individuals with an AUD. As such, there is a need to develop new, more effective, and diverse pharmacological treatment options for AUD with the hopes of increasing utilization and improving care. In this qualitative literature review, we discuss the efficacy, mechanism of action, and tolerability of approved, repurposed, and novel pharmacotherapies for the treatment of AUD with a clinical perspective. Pharmacotherapies discussed include: disulfiram, acamprosate, naltrexone, nalmefene, topiramate, gabapentin, varenicline, baclofen, sodium oxybate, aripiprazole, ondansetron, mifepristone, ibudilast, suvorexant, prazosin, doxazosin, N-acetylcysteine, GET73, ASP8062, ABT-436, PF-5190457, and cannabidiol. Overall, many repurposed and novel agents discussed in this review demonstrate clinical effectiveness and promise for the future of AUD treatment. Importantly, these medications also offer potential improvements towards the advancement of precision medicine and personalized treatment for the heterogeneous AUD population. However, there remains a great need to improve access to treatment, increase the menu of approved pharmacological treatments, and de-stigmatize and increase treatment-seeking for AUD.

Sex-Related Differences in Voluntary Alcohol Intake and mRNA Coding for Synucleins in the Brain of Adult Rats Prenatally Exposed to Alcohol

“…Importantly, α-synuclein is highly expressed in the excitatory synapses marked by vesicular glutamate transporter-1 [ 53 , 54 ] and believed to be involved in mobilization of glutamate from the reserve pool [ 55 ]. Since glutamate plays a principle role in alcohol seeking, alcohol addiction and relapse [ 56 , 57 , 58 ] and chronic alcohol treatment promotes abnormal synaptic transmission that may lead to hippocampal cell death resulted from glutamate excitotoxicity after ethanol withdrawal [ 59 ]. Taking into account that α-synuclein knockout mice have cognitive impairments [ 60 ] we can suggest that the identified effect of downregulation of α-synuclein mRNA in HPC, perhaps, may be partly responsible for cognitive deficit which is typical for PAE offspring [ 61 , 62 ].…”

Off-label and investigational drugs in the treatment of alcohol use disorder: A critical review

“…As shown in detail above, several different drugs and medication classes have been investigated for their potential use in the treatment of alcohol use disorder, a clinical area where there is a desperate need for new treatment strategies ( Burnette et al, 2022 ). Some have shown very promising results, while others have not proven useful.…”

Updates in Prevalence, Risk Factors, Management and Outcome of Treatment of Acute Pancreatitis

“…All patients with known AP should receive abstinence counseling [43]. A randomized controlled trial showed that abstinence counseling during AP reduced the recurrence rate of AP over 2 years [44].…”