Investigational drug therapies in phase I and phase II clinical trials for alcohol use disorders

ABSTRACT

Introduction: Alcohol use disorder (AUD) is a complex psychiatric condition characterized by craving, compulsive seeking, loss of control of alcohol consumption as well as the emergence of negative emotional states during withdrawal. Despite the large socioeconomic burden of AUD, therapeutic treatment options lag behind.

Areas covered: This review covers pharmacotherapies currently in phase I/II clinical trials for the treatment of AUDs listed on clinicaltrials.gov. We discuss drug therapies that modulate monoamine, GABA/Glutamate, neuropeptide and neuroimmune systems. We examine in depth preclinical and clinical evidence of a select range of these compounds and consider their utility in treating AUDs.

Expert opinion: Current therapeutic options to treat AUD are inadequate at a population level. Currently there are 30 different compounds and one compound combination in phase I/II clinical trials for AUD. These compounds target various aspects of neurotransmitter signaling, neuroimmune modulation, and alcohol metabolism. Almost 75% of these compounds under trial are Food and Drug Administration (FDA) approved for other indications, which may save time and costs in treatment development. Further, development of therapeutics focused on genetic biomarkers and behavioral screening may improve how treatment decisions are made in the future on a case-by-case basis.

KEYWORDS:

• Alcohol use disorder
• clinical trial
• pharmacotherapies
• drug repurposing
• precision medicine

Article highlights

• Current therapeutics to treat AUDs are inadequate and development of new pharmacotherapies are lagging

• There are 30 different compounds and one compound combination currently in phase I/II clinical trial for AUD targeting various aspects of neurotransmitter signaling, neuroimmune modulation, and alcohol metabolism

• Several compound in clinical trial including oxytocin, modafinil and ondansetron show promise for future development

• Repurposing already FDA approved pharmacotherapies is an effective and economically feasible approach for AUD drug development

• Genetic and behavioral screening may be useful to determine the most appropriate therapeutic treatment(s) on an individual basis

This box summarizes key points contained in the article.

Declaration of Interest

The authors have no 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.

Additional information

Funding

This work was supported by a National Health and Medical Research Council Project Grant (AJL, 1120576), a National Health and Medical Research Council Principal Research Fellowship (AJL, 1116930) and the Victorian State Government Operational Infrastructure Scheme.