Medications development for the treatment of alcohol use disorder: insights into the predictive value of animal and human laboratory models

Abstract

Development of effective treatments for alcohol use disorder (AUD) represents an important public health goal. This review provides a summary of completed preclinical and clinical studies testing pharmacotherapies for treatment of AUD. We discuss opportunities for improving the translation from preclinical findings to clinical trial outcomes, focusing on the validity and predictive value of animal and human laboratory models of AUD. Specifically, while preclinical studies of medications development have offered important insights into the neurobiology of the disorder and alcohol's molecular targets, limitations include the lack of standardized methods and streamlined processes whereby animal studies can readily inform human studies. Behavioral pharmacology studies provide a less expensive and valuable opportunity to assess the feasibility of a pharmacotherapy prior to initiating larger scale clinical trials by providing insights into the mechanism of the drug, which can then inform recruitment, analyses, and assessments. Summary tables are provided to illustrate the wide range of preclinical, human laboratory, and clinical studies of medications development for alcoholism. Taken together, this review highlights the challenges associated with animal paradigms, human laboratory studies and clinical trials with the overarching goal of advancing treatment development and highlighting opportunities to bridge the gap between preclinical and clinical research.

Differences between treatment-seeking and non-treatment-seeking participants in medication studies for alcoholism: do they matter?

“…While individuals with AUD who enroll in behavioral pharmacology studies may reduce their drinking over the course of study participation and after brief intervention [2], the extent to which non-treatment seeking samples are representative of treatment-seeking samples in randomized controlled trials for AUD remains poorly understood. Oftentimes, findings from human laboratory studies do not consistently and reliably translate to clinical trials outcomes [3]. Although reasons for these discrepancies remain unknown, one possibility is that treatment-seeking individuals respond differently to medications compared to non-treatment seeking individuals.…”

Experimental psychopathology paradigms for alcohol use disorders: Applications for translational research

“…By utilizing multiple paradigms, treatment development studies stand a better chance to determine therapeutic mechanisms of action and more effectively screen medications (Ray, Hutchison, et al, 2010). Though this strategy increases the likelihood of effective treatment screening, further research is needed to determine the degree to which these experimental psychopathology paradigms translate to treatment outcomes (Yardley & Ray, 2016). …”

The Role of Psychotropic Medications in the Management of Anorexia Nervosa: Rationale, Evidence and Future Prospects

“…What animal models do not represent well are the cognitive-emotional aspects of AN and its ego-syntonic nature of food restriction [137]. Another caveat to keep in mind from substance use disorder treatment research is that drug development can show much promise in animals, but not all of these results can be directly translated to humans [138]. …”