https://orcid.org/0000-0001-5856-873X
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ABSTRACT
Introduction
Alcohol Use Disorder (AUD) poses an ongoing significant global health burden. AUD is highly prevalent and affects not only the individuals with AUD, but also their communities and society at large. Even though pharmacotherapy is an integral part of AUD treatment, the few available substances show limited efficacy and limited clinical impact. Thus, there is a need for new innovative pharmacotherapeutic approaches.
Areas covered
This paper provides a comprehensive review of drugs approved for the treatment of AUD as well as those currently in phase II and III development. Data from recent clinical trials has been reviewed and supplemented by additional literature based on a systematic search of the PubMed database and clinical trials registries. Compounds discussed include disulfiram, naltrexone, nalmefene, acamprosat, baclofen, sodium oxybate, doxazosin, varenicline, zonisamide, gabapentin, apremilast, ibudilast, ivermectin, tolcapone, mifepristone, suvorexant, ketamine, psilocybin, semaglutide, oxytocin and cannabidiol.
Expert Opinion
Even though the majority of the discussed compounds lack sufficient evidence to support their efficacy, multiple promising new treatment options are currently under investigation. Future research has to consider specific phenotypes and subgroups of AUD as well as a possible enhancement of the effects of psychotherapy through combination with pharmacotherapy. Practitioners should be encouraged to use available compounds to support existing therapeutic regimens.
Article highlights
AUD is a significant global health issue with a severe socioeconomic impact.
There are various pharmaceutical treatment options that use different pathways to improve outcomes.- Approved treatment options are currently underutilized.
Several pharmacologic agents are being repurposed to treat AUD and have shown promising early results, although more evidence is needed.
Personalized pharmacological treatment reflecting different phenotypes of AUD could improve treatment.
Abbreviations
| ADH | = | aldehyde dehydrogenase |
| ANSM | = | Agence nationale de sécurité du médicament et des produits de santé |
| AUD | = | alcohol use disorder |
| CBD | = | cannabidiol |
| COMT | = | catechol–O–methyl transferase |
| DALYs | = | disability–adjusted life-years |
| DER | = | disulfiram–ethanol reaction |
| DSM–5 | = | Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) |
| EMA | = | European Medicines Agency |
| FDA | = | Food and Drug Administration |
| fMRI | = | functional magnetic resonance imaging |
| GABA | = | γ–aminobutyric acid |
| GE–XR | = | Gabapentin Enacarbil Extended-Release |
| GHB | = | γ–hydroxybutyric acid |
| GLP–1 | = | Glucagon-like Peptide 1 |
| IU | = | international units |
| MD | = | mean difference |
| NCT | = | National Clinical Trials |
| NICE | = | National Institute for Health and Care Excellence |
| NMDA | = | N–methyl–D–Aspartate |
| NNT | = | number needed to treat |
| PDE4 | = | phosphodiesterase type 4 |
| PTSD | = | post–traumatic stress disorder |
| RCT | = | randomized controlled trial |
| RR | = | relative risk |
| SEM | = | semaglutide |
| SMO | = | sodium oxybate |
| THC | = | delta–9–tetrahydrocannabinol |
| XR-NTX | = | extended–release naltrexone |
Declaration of interest
P Bach received public funding by the German Ministry of Science and Education (ON-ICE Trial) and private funding by the Hetzler foundation in the framework of two investigator-initiated trials (without company involvement) investigating the effects of naltrexone and oxytocin on alcohol craving and the effects of cannabidiol on alcohol craving in individuals with alcohol use disorder respectively.
A Glahn received private funding from the ‘Hetzler Foundation’ to investigate the influence of alcohol on the microbiome and funding from the ‘Hochschulinterne Leistungsförderung (HILF)’ to investigate epigenetic changes during nicotine withdrawal.
The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Reviewer disclosure
A reviewer on this manuscript has disclosed that they are President of ABMRF, the Foundation for Alcohol Research and a member of the Board of Directors of Amygdala Neuroscience. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.