Khoshnevis Sepideh, Smolensky Michael H, Haghayegh Shahab
Department of Biomedical Engineering, Cockrell School of Engineering, The University of Texas at Austin, Austin, TX, USA.
Department of Biomedical Engineering, Cockrell School of Engineering, The University of Texas at Austin, Austin, TX, USA; Department of Internal Medicine, Division of Cardiology, McGovern School of Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Adv Drug Deliv Rev. 2025 Aug;223:115576. doi: 10.1016/j.addr.2025.115576. Epub 2025 Apr 3.
This review focuses on (i) 24 h patterns in the symptom intensity of common neurologic and psychiatric disorders and (ii) medications prescribed for their management that have a recommended administration time or schedule, presumably to potentiate desired and minimize undesired effects and by definition qualify them as chronotherapies. Predictable-in-time patterning of symptoms is exhibited by many neurologic -- headaches, multiple sclerosis, neurogenic orthostatic hypotension, neuropathic pain, Parkinson's disease, epileptic seizure, attention deficit hyperactivity, Alzheimer's disease - and psychiatric - eating, depressive, obsessive-compulsive, post-traumatic stress, anxiety, and panic - disorders, due either to circadian rhythms of disease pathophysiology or inadequacies of medication-delivery systems. Circadian disruption and circadian misalignment of the sleep-wake and other 24 h rhythms plus late chronotype are characteristic of many of these disorders, suggesting involvement in the mechanisms or consequence of their pathology or as an adverse effect of therapy, especially when administered at an inappropriate biological time. The Prescribers' Digital Reference, a compendium of all prescription medications approved for marketing in the US, reveals 65 of them are utilized to manage neurologic and psychiatric disorders by a specified time-of-day or an asymmetrical interval or strength of dose schedule, presumably to optimize beneficial and minimize adverse effects, thereby qualifying them as chronotherapies. Overall, the contents of this review are intended to inform the development of future chronotherapies that incorporate state-of-the-art drug-delivery systems to improve management of neurologic and psychiatric disorders and associated circadian malalignment and disruption.
（i）常见神经和精神疾病症状强度的24小时模式，以及（ii）为治疗这些疾病而开具的具有推荐给药时间或时间表的药物，推测这些药物可增强预期效果并将不良影响降至最低，从定义上讲，它们属于时辰疗法。许多神经疾病（头痛、多发性硬化症、神经源性直立性低血压、神经性疼痛、帕金森病、癫痫发作、注意力缺陷多动障碍、阿尔茨海默病）和精神疾病（饮食失调、抑郁症、强迫症、创伤后应激障碍、焦虑症和恐慌症）都表现出症状在时间上的可预测模式，这要么是由于疾病病理生理学的昼夜节律，要么是由于药物递送系统的不足。昼夜节律紊乱、睡眠-觉醒及其他24小时节律的昼夜失调以及晚睡型是这些疾病中的许多疾病的特征，这表明其参与了疾病病理机制或后果，或者是治疗的不良反应，尤其是在不适当的生物时间给药时。《处方者数字参考》是美国批准上市的所有处方药的汇编，其中显示有65种药物被用于通过特定的每日时间、不对称的间隔或剂量时间表强度来治疗神经和精神疾病，推测是为了优化益处并将不良反应降至最低，从而使其符合时辰疗法的标准。总体而言，本综述的内容旨在为未来时辰疗法的发展提供信息，这些疗法将采用最先进的药物递送系统，以改善神经和精神疾病的管理以及相关的昼夜失调和紊乱。
