Neuroscience Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA, USA.
Department of Psychology, University of California, Los Angeles, Los Angeles, CA, USA.
Pharmaceut Med. 2024 Jul;38(4):291-302. doi: 10.1007/s40290-024-00526-x. Epub 2024 Jul 5.
Alcohol use disorder (AUD) is a debilitating disorder, yet currently approved pharmacotherapies to treat AUD are under-utilized. The three medications approved by the US Food and Drug Administration (FDA) for the indication of AUD are disulfiram, acamprosate, and naltrexone. The current landscape of pharmacotherapies for AUD suggests opportunities for improvement. Clinical trials investigating novel pharmacotherapies for AUD traditionally use abstinence-based drinking outcomes or no heavy drinking days as trial endpoints to determine the efficacy of pharmacotherapies. These outcomes are typically measured through patient self-report endorsements of their drinking. Apart from these traditional outcomes, there have been recent developments in novel endpoints for AUD pharmacotherapies. These novel endpoints include utilizing the World Health Organization (WHO) risk drinking level reductions to promote a harm-reduction endpoint rather than an abstinence-based endpoint. Additionally, in contrast to patient self-report measurements, biological markers of alcohol use may serve as objective endpoints in AUD pharmacotherapy trials. Lastly, the National Institute on Alcohol Abuse and Alcoholism (NIAAA) definition of recovery from AUD and patient-oriented outcomes offer new frameworks to consider endpoints associated with more than alcohol consumption itself, such as the provider-patient experiences with novel pharmacotherapies. These recent developments in new endpoints for AUD pharmacotherapies offer promising future opportunities for pharmacotherapy development, so long as validity and reliability measures are demonstrated for the endpoints. A greater breadth of endpoint utilization may better capture the complexity of AUD symptomatology.
酒精使用障碍（AUD）是一种使人衰弱的疾病，但目前用于治疗 AUD 的已批准药物治疗方法并未得到充分利用。美国食品和药物管理局（FDA）批准用于 AUD 适应证的三种药物是双硫仑、安非他酮和纳曲酮。目前 AUD 药物治疗的现状表明存在改进的机会。传统上，用于 AUD 的新型药物治疗的临床试验使用基于戒断的饮酒结果或无重度饮酒天数作为试验终点来确定药物治疗的疗效。这些结果通常通过患者自我报告对其饮酒的认可来衡量。除了这些传统结果外，AUD 药物治疗的新终点最近也有了一些发展。这些新的终点包括利用世界卫生组织（WHO）降低风险饮酒水平，以促进减少伤害的终点，而不是基于戒断的终点。此外，与患者自我报告的测量相比，酒精使用的生物标志物可能作为 AUD 药物治疗试验的客观终点。最后，国家酒精滥用和酒精中毒研究所（NIAAA）对 AUD 康复的定义和以患者为中心的结果提供了新的框架，以考虑与酒精消费本身相关的新终点，例如提供者-患者对新型药物治疗的体验。只要为终点提供了有效性和可靠性措施，AUD 药物治疗新终点的这些最新进展为药物治疗开发提供了有前途的未来机会。更广泛的终点利用可能更好地捕捉 AUD 症状的复杂性。
