Novel medications for problematic alcohol use

Abstract

Alcohol-related harm, a major cause of disease burden globally, affects people along a spectrum of use. When a harmful pattern of drinking is present in the absence of significant behavioral pathology, low-intensity brief interventions that provide information about health consequences of continued use provide large health benefits. At the other end of the spectrum, profound behavioral pathology, including continued use despite knowledge of potentially fatal consequences, warrants a medical diagnosis, and treatment is strongly indicated. Available behavioral and pharmacological treatments are supported by scientific evidence but are vastly underutilized. Discovery of additional medications, with a favorable balance of efficacy versus safety and tolerability can improve clinical uptake of treatment, allow personalized treatment, and improve outcomes. Here, we delineate the clinical conditions when pharmacotherapy should be considered in relation to the main diagnostic systems in use and discuss clinical endpoints that represent meaningful clinical benefits. We then review specific developments in three categories of targets that show promise for expanding the treatment toolkit. GPCRs remain the largest category of successful drug targets across contemporary medicine, and several GPCR targets are currently pursued for alcohol-related indications. Endocrine systems are another established category, and several promising targets have emerged for alcohol indications. Finally, immune modulators have revolutionized treatment of multiple medical conditions, and they may also hold potential to produce benefits in patients with alcohol problems.

Figure 1. Schematic of approval process for medication development, as outlined by the US FDA.

Figure 2. Schematic of putative entero- and neuroendocrine mechanisms that can be targeted by medications for AD.

AG, acyl-ghrelin (also known as ghrelin); AgRP, agouti-related peptide; CNS, central nervous system; DAG, des-acyl-ghrelin; DNA, deoxyribonucleic acid; GH, growth hormone; GLP-1, glucagon-like peptide-1; GOAT, ghrelin O-acyltransferase; NPY, neuropeptide Y; POMC, pro-opiomelanocortin.