IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, Victoria, Australia.
Mental Health, Drugs and Alcohol Services, University Hospital Geelong, Barwon Health, Geelong, Victoria, Australia.
Early Interv Psychiatry. 2019 Oct;13(5):1032-1049. doi: 10.1111/eip.12775. Epub 2019 Jan 28.
Neuropsychiatric disorders including depression, bipolar and schizophrenia frequently exhibit a neuroprogressive course from prodrome to chronicity. There are a range of agents exhibiting capacity to attenuate biological mechanisms associated with neuroprogression. This review will update the evidence for putative neuroprotective agents including clinical efficacy, mechanisms of action and limitations in current assessment tools, and identify novel agents with neuroprotective potential.
Data for this review were sourced from online databases PUBMED, Embase and Web of Science. Only data published since 2012 were included in this review, no data were excluded based on language or publication origin.
Each of the agents reviewed inhibit one or multiple pathways of neuroprogression including: inflammatory gene expression and cytokine release, oxidative and nitrosative stress, mitochondrial dysfunction, neurotrophin dysregulation and apoptotic signalling. Some demonstrate clinical efficacy in preventing neural damage or loss, relapse or cognitive/functional decline. Agents include: the psychotropic medications lithium, second generation antipsychotics and antidepressants; other pharmacological agents such as minocycline, aspirin, cyclooxygenase-2 inhibitors, statins, ketamine and alpha-2-delta ligands; and others such as erythropoietin, oestrogen, leptin, N-acetylcysteine, curcumin, melatonin and ebselen.
Signals of evidence of clinical neuroprotection are evident for a number of candidate agents. Adjunctive use of multiple agents may present a viable avenue to clinical realization of neuroprotection. Definitive prospective studies of neuroprotection with multimodal assessment tools are required.
包括抑郁症、双相情感障碍和精神分裂症在内的神经精神疾病通常表现出从前驱期到慢性期的神经进行性过程。有一系列药物具有减轻与神经进行性相关的生物学机制的能力。本综述将更新包括临床疗效、作用机制和当前评估工具局限性在内的潜在神经保护剂的证据，并确定具有神经保护潜力的新型药物。
本综述的数据来源于 PUBMED、Embase 和 Web of Science 在线数据库。本综述仅纳入了自 2012 年以来发表的数据，没有基于语言或出版来源排除任何数据。
所审查的每种药物都抑制了神经进行性的一个或多个途径，包括：炎症基因表达和细胞因子释放、氧化和硝化应激、线粒体功能障碍、神经营养素失调和细胞凋亡信号。其中一些药物在预防神经损伤或损失、复发或认知/功能下降方面显示出临床疗效。这些药物包括：精神药物锂、第二代抗精神病药和抗抑郁药；其他药理学药物，如米诺环素、阿司匹林、环氧化酶-2 抑制剂、他汀类药物、氯胺酮和α-2-δ 配体；以及其他药物，如促红细胞生成素、雌激素、瘦素、N-乙酰半胱氨酸、姜黄素、褪黑素和依布硒啉。
许多候选药物的临床神经保护证据信号明显。联合使用多种药物可能是实现神经保护的可行途径。需要使用多模态评估工具进行明确的前瞻性神经保护研究。
