Reductions in World Health Organization Risk Drinking Levels as a Primary Efficacy End Point for Alcohol Clinical Trials

作者：Katie Witkiewitz, Raymond F. Anton, Stephanie S. O’Malley, Deborah S. Hasin, Bernard L. Silverman, Arnie Aldridge, Karl Mann, Henry R. Kranzler, Henri‐Jean Aubin, Michaela Hoffman, Conrad J. Wong, Didier Meulien, Gary A. Zarkin · 发表于：JAMA Psychiatry · 年份：2025 · DOI：10.1001/jamapsychiatry.2025.2508 · 被引用次数：27 · 研究领域：Substance Abuse Treatment and Outcomes、Alcoholism and Thiamine Deficiency、Alcohol Consumption and Health Effects

Importance: Alcohol use disorder (AUD) is a highly prevalent and costly psychiatric disorder. Abstinence has been considered the optimal outcome of treatment for AUD. Yet, most individuals with AUD do not seek treatment because they do not have a goal of abstinence. The Food and Drug Administration (FDA) has recently qualified reductions in drinking, defined by at least a 2-level reduction in the World Health Organization risk drinking levels (WHO RDLs), as a primary end point for alcohol pharmacotherapy trials. The approval of drinking reductions as an end point for alcohol clinical trials aligns with an accumulating literature on drinking reductions in the alcohol field. This article provides a narrative review of 34 articles that have examined WHO RDLs as a surrogate marker of how people with AUD feel and function. Observations: Results from epidemiological studies, community samples, and clinical trials indicate that drinking reductions are associated with improvements in how patients feel and function, including reduced risk of substance use disorder and medical and psychiatric diseases and reductions in alcohol-related consequences, craving, and health care costs. Drinking reductions are also associated with improvements in functioning and quality of life. Drinking reductions are also achieved by most clinical trial participants, and effect sizes for the WHO RDL reductions for active medications vs placebo are similar to or better than alternative end points. Conclusion...