Along with cognitive decline, 90% of patients with dementia experience behavioral and psychological symptoms of dementia, such as psychosis, aggression, agitation, and depression. Atypical antipsychotics are commonly prescribed off-label to manage certain symptoms, despite warnings from the regulatory agencies regarding the increased risk of mortality associated with their use in elderly patients. Moreover, these compounds display a limited clinical efficacy, mostly owing to the fact that they were developed to treat schizophrenia, a disease characterized by neurobiological deficits. Thus, to improve clinical efficacy, it has been suggested that patients with dementia should be treated with exclusively designed and developed drugs that interact with pharmacologically relevant targets. Within this context, numerous studies have suggested druggable targets that might achieve therapeutically acceptable pharmacological profiles. Based on this, several different drug candidates have been proposed that are being investigated in clinical trials for behavioral and psychological symptoms of dementia. We highlight the recent advances toward the development of therapeutic agents for dementia-related psychosis and agitation/aggression and discuss the relationship between the relevant biological targets and their etiology. In addition, we review the compounds that are in the early stage of development (discovery or preclinical phase) and those that are currently being investigated in clinical trials for dementia-related psychosis and agitation/aggression. We also discuss the mechanism of action of these compounds and their pharmacological utility in patients with dementia.

中文翻译：

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与痴呆症有关的精神病，躁动和攻击的管理：潜在候选药物的药理作用和临床效果的综述。

除认知能力下降外，90％的痴呆患者还患有痴呆的行为和心理症状，例如精神病，攻击性，激动和抑郁。尽管监管机构警告说，在老年患者中使用非典型抗精神病药会增加其死亡风险，但非处方抗精神病药通常要贴标签处理某些症状。此外，这些化合物显示出有限的临床功效，主要是由于它们被开发用于治疗精神分裂症（一种以神经生物学缺陷为特征的疾病）的事实。因此，为了提高临床疗效，已建议痴呆症患者应使用专门设计和开发的与药理学相关靶标相互作用的药物进行治疗。在这种情况下，大量研究表明可药物治疗的靶点可能达到治疗可接受的药理学特征。基于此，已经提出了针对痴呆症的行为和心理症状进行临床试验研究的几种不同的候选药物。我们重点介绍了痴呆症相关的精神病和躁动/攻击治疗剂开发的最新进展，并讨论了相关生物学目标与其病因之间的关系。此外，我们回顾了处于开发早期（发现或临床前阶段）的化合物，以及目前正在临床试验中研究的与痴呆症相关的精神病和躁动/攻击性化合物。