New antipsychotic drugs for the treatment of agitation and psychosis in Alzheimer's disease: focus on brexpiprazole and pimavanserin.
New antipsychotic drugs for the treatment of agitation and psychosis in Alzheimer's disease: focus on brexpiprazole and pimavanserin.
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DOI：
10.12688/f1000research.22662.1
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发表时间：
2020-01-01
期刊：
影响因子：
--
通讯作者：
Drago, Filippo
中科院分区：
文献类型：
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作者：
Caraci, Filippo;Santagati, Mario;Drago, Filippo
痴呆症的行为和心理症状是经常发生的知觉、情绪、行为和思想内容紊乱的症状。这些症状包括冷漠、抑郁、焦虑、精神病、躁动和攻击性，可以作为阿尔茨海默病(AD)的预测指标和早期临床诊断标志，也是机构护理的常见诱因。激越和精神错乱与AD患者疾病进展加速和tau磷酸化增加有关。目前的指南建议使用第二代抗精神病药物治疗AD患者的躁动和精神病，但只能在一线非药物干预之后使用，而且不超过12周，因为长期使用这些药物会增加死亡风险和脑血管事件的频率。因此，需要更有效、更安全的新型抗精神病药物来替代现有的抗精神病药物。在这份报告中，我们讨论了在AD的激越和精神病领域的一些最相关的进展，并集中在两种新的抗精神病药物：布雷西哌唑和吡喃色林最近观察到的积极的临床证据。根据神经科学的命名，布雷西哌唑是一种受体部分激动剂(D2，D3，5-HT1A)，受体拮抗剂(5-HT2A/B，α1B/α2C)。最近的两项III期临床试验表明，布雷克哌唑每天2毫克对阿尔茨海默病患者的躁动症状有效，与目前可用的第二代抗精神病药物相比，其耐受性和安全性都有所改善。Pimavanserin是一种受体拮抗剂(5-HT2A，5-HT2C)，已被市场批准用于治疗帕金森氏病中的精神病。最近的第二阶段研究表明，这种药物对患有更严重精神病的AD患者有效，尽管还需要进一步的长期研究，以更好地确定吡喃色林治疗AD精神病的有效性和长期安全性。
Behavioral and psychological symptoms of dementia are symptoms of disturbed perception, mood, behavior, and thought content that occurred frequently. These symptoms, which include apathy, depression, anxiety, psychosis, agitation, and aggression, can serve as predictors of and early clinical diagnostic markers for Alzheimer's disease (AD) and are common precipitants of institutional care. Agitation and psychosis are associated with accelerated disease progression and increased tau phosphorylation in patients with AD. Current guidelines recommend the use of second-generation antipsychotics for the treatment of agitation and psychosis in AD, but only after first-line non-pharmacological interventions and for no longer than 12 weeks because long-term use of these drugs is associated with an increased risk of mortality and an increased frequency of cerebrovascular events. Therefore, new antipsychotic drugs with improved efficacy and safety are needed as an alternative to current antipsychotic drugs. In this report, we discuss some of the most relevant advances in the field of agitation and psychosis in AD and focus on the recent positive clinical evidence observed with two new antipsychotics drugs: brexpiprazole and pimavanserin. Brexpiprazole is a receptor partial agonist (D2, D3, 5-HT1A), receptor antagonist (5-HT2A/B, alpha1B/alpha2C) according to the neuroscience-based nomenclature. Two recent phase III clinical trials have shown that brexpiprazole 2 mg/day is effective for the treatment of agitation in patients with AD and has an improved tolerability and safety profile compared with currently available second-generation antipsychotics. Pimavanserin is a receptor antagonist (5-HT2A, 5-HT2C) that has been given market authorization for psychosis occurring in Parkinson's disease. Recent phase II studies suggest that this drug is effective in AD patients with more severe psychosis, although further long-term studies are needed to better define the efficacy and long-term safety profile of pimavanserin for the treatment of psychosis in AD.