Abstract：
The opioid crisis is an international public health concern. Treatments for opioid use disorder centre largely on the management of opioid withdrawal, an aversive collection of signs and symptoms that contribute to opioid use disorder. Whereas in the past 50 years more than 90 medications have been developed for depression, only five medications have been developed for opioid use disorder during this period. We posit that underinvestment has occurred in part due to an underdeveloped understanding of opioid withdrawal syndrome. This Personal View summarises substantial gaps in our understanding of opioid withdrawal that are likely to continue to limit major advancements in its treatment. There is no firm consensus in the field as to how withdrawal should be precisely defined; 10-550 symptoms of withdrawal can be measured on 18 scales. The imprecise understanding of withdrawal is likely to result in overestimating or underestimating the severity of an individual\'s withdrawal syndrome or potential therapeutic effects of different candidate medications. The severity of the opioid crisis is not remitting, and an international research agenda for the study and assessment of opioid withdrawal is necessary to support transformational changes in withdrawal management and treatment of opioid use disorder. Nine actionable targets are delineated here: develop a consensus definition of opioid withdrawal; understand withdrawal symptomatology after exposure to different opioids (particularly fentanyl); understand precipitated opioid withdrawal; understand how co-exposure of other drugs (eg, xylazine and stimulants) influences withdrawal expression; examine individual variation in withdrawal phenotypes; precisely characterise the protracted withdrawal syndrome; identify biomarkers of opioid withdrawal severity; identify predictors of opioid withdrawal severity; and understand which symptoms are most closely associated with treatment attrition or relapse. The US Food and Drug Administration recently established a formal indication for opioid withdrawal that has invigorated interest in drug development for opioid withdrawal management. Action is now needed to support these interests and help industry identify new classes of medications so that real change can be achieved for people with opioid use disorder.
摘要：
阿片类药物危机是一个国际公共卫生问题。阿片类药物使用障碍的治疗主要集中在阿片类药物戒断的管理上，导致阿片类药物使用障碍的一系列令人厌恶的体征和症状。在过去的50年里，已经开发了90多种治疗抑郁症的药物，在此期间，只有五种药物被开发用于阿片类药物使用障碍。我们认为，投资不足的部分原因是对阿片类药物戒断综合征的理解不足。这种个人观点总结了我们对阿片类药物戒断的理解中的巨大差距，这些差距可能会继续限制其治疗的重大进步。关于如何精确定义戒断，该领域没有明确的共识；可以在18个量表上测量10-550种戒断症状。对戒断的不精确理解可能导致高估或低估个体戒断综合征的严重程度或不同候选药物的潜在治疗效果。阿片类药物危机的严重程度并没有减轻，和阿片类药物戒断的研究和评估的国际研究议程是必要的，以支持戒断管理和阿片类药物使用障碍治疗的转型变化。这里描述了九个可行的目标:制定阿片类药物戒断的共识定义;了解暴露于不同阿片类药物(特别是芬太尼)后的戒断症状;了解阿片类药物的沉淀戒断;了解其他药物的共同暴露(例如，赛拉嗪和兴奋剂）影响戒断表达；检查戒断表型的个体差异；精确表征长期戒断综合征；确定阿片类戒断严重程度的生物标志物；确定阿片类戒断严重程度的预测因子；并了解哪些症状与治疗减员或复发最密切相关。美国食品和药物管理局最近建立了阿片类药物戒断的正式适应症，这激发了人们对阿片类药物戒断管理药物开发的兴趣。现在需要采取行动来支持这些利益，并帮助行业确定新的药物类别，以便为阿片类药物使用障碍患者实现真正的改变。
