New approved and emerging pharmacological approaches to alcohol use disorder: a review of clinical studies

ABSTRACT

Abstract introduction: The number of medications approved for AUD is small and they generally have limited efficacy. We need new pharmacotherapies for the management of AUD.

Areas covered: In this review, the authors aim to synthesise literature for new approved and emerging pharmacotherapies for AUD. Recently approved medications include nalmefene, which was approved in Europe and Australia for the purposes of controlled drinking. Baclofen has also been approved in France but not in other countries. Off label medications including topiramate and gabapentin have received significant attention with multiple RCTs and meta-analyses and have widespread use in several countries including the USA. Several novel medications have emerged over the last decade but further work is required to determine their efficacy and safety for the widespread management of AUD.

Expert opinion: Despite significant advances in our understanding of the neurobiological basis of factors that contribute to the development and maintenance of AUD, there have been few new AUD medications approved for almost 20 years. There are many challenges to the development and introduction of new pharmacotherapies for AUD. Strategies for improving the translational pipeline include drug repurposing and utilisation of human acute laboratory models.

KEYWORDS:

• Alcohol use disorder
• pharmacotherapy
• Phase II
• Phase 1b
• clinical trials

Article highlights

1. The number of medications approved for AUD is small and they generally have limited efficacy (naltrexone, acamprosate and disulfiram).

2. Recently approved medications include nalmefene, which was approved in Europe and Australia and baclofen, which has only been approved in France.

3. Off-label medications including topiramate and gabapentin have received significant attention with multiple RCTs and meta-analyses.

4. Several novel medications have emerged in Phase 1b and II trials yielding mixed results in terms of efficacy and safety including drugs targeting the acetylcholine system (varenicline, citicoline), the glutamate system (ifenprodil, ketamine), stress systems (prazosin and doxazosin, pexacerfont and verucerfont, and oxytocin and ABT-436) and other systems (ghrelin, ibudilast).

5. Agents currently under trial include cannabidiol (CBD), probenecid, 3,4-methylenedioxymethamphetamine (MDMA), suvorexant and N-acetylcysteine (NAC).

6. Strategies for improving the translational pipeline include drug repurposing and utilization of human acute laboratory models, in addition to enhanced understanding of personalized medicine approaches including pharmacogenetics and impact of comorbidities.

This box summarizes key points contained in the article.

Declaration of interest

P Haber has served on advisory boards for Lundbeck who developed nalmefene for the treatment of AUD. 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.

Acknowlegments

K Morley, C Perry, P Haber, and A Lawrence acknowledge support from the for alcohol research.

National Health and Medical Research Council (NHMRC) for alcohol research.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

K Morley is supported by the NSW Health Fellowship. P Haber is supported by the NHMRC Practitioner Research Fellowship, while L. Leggio has received support from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute of Drug Abuse.