Pharmacotechnology Documentation and Transfer Unit, Preclinical and Translational Pharmacology, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy; Regional Center for Serious Brain Injuries, S. Anna Institute, Crotone, Italy.
Department of Health Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.
Curr Opin Pharmacol. 2021 Dec;61:69-76. doi: 10.1016/j.coph.2021.09.002. Epub 2021 Oct 9.
Abnormal neuronal and synaptic plasticity occurs in Alzheimer's disease (AD) and depression. The latter, particularly late-life, has been recognized as fundamental in the identification of at-risk prodromal stages of AD. The lack of disease-modifying drugs and the off-label use of antipsychotics and antidepressants for neuropsychiatric symptoms (NPSs) have caused a season of therapeutic inappropriateness. To date, the wealth of clinical trials investigating drugs, diverse for structure and mechanism of action, has failed to provide a cure for all the spectrums of NPSs. Psychedelics in microdosing afford promotion of neurogenesis and synaptic plasticity and, recently, have been considered a revolution for the management of depression endowed with faster action and an improved side effect profile than antidepressants. In the current scenario, therefore, the rapid-acting antidepressant esketamine could represent the first-in-class for treatment of NPSs, and this deserves to be demonstrated with an open-label clinical trial.
阿尔茨海默病（AD）和抑郁症患者存在异常的神经元和突触可塑性。后者，尤其是老年期抑郁症，已被认为是识别 AD 高危前驱期的重要因素。由于缺乏能够改变疾病进程的药物，以及抗精神病药和抗抑郁药被超适应证用于治疗神经精神症状（NPSs），导致治疗时机不当的情况频频发生。迄今为止，大量临床试验针对不同结构和作用机制的药物进行了研究，但未能为所有 NPSs 提供治愈方法。低剂量致幻剂可促进神经发生和突触可塑性，最近被认为是治疗抑郁症的一场革命，其作用更快，副作用谱优于抗抑郁药。因此，在当前情况下，快速起效的抗抑郁药依他佐辛可能是治疗 NPSs 的首创药物，这值得通过一项开放标签临床试验来证实。
