阿尔茨海默病(Alzheimer\'sdisease,AD)是一种以进行性认知功能减退为特征的常见神经退行性疾病。几乎所有AD患者都会出现神经精神症状(NPS)。躁动是最令人痛苦和具有挑战性的NPS之一。Brexpiprazole是一种口服抗精神病药物,是美国第一个被批准用于治疗与AD引起的痴呆相关的躁动的药物。其作用被认为来自其部分5-羟色胺5-HT1A和多巴胺D2受体激动剂活性和5-羟色胺5-HT2A受体拮抗作用。Brexpiprazole是一种维持药物,并且不应“根据需要”或“PRN”治疗突破性躁动。Brexiprazole是CYP2D6和CYP3A4的主要底物。药物相互作用或肾功能或肝功能受损可能需要剂量调整。临床试验发现,2至3毫克/天的布立哌唑在躁动方面显着改善,与安慰剂组相比,在第12周时,在Cohen-Mansfield躁动量表总分的变化方面,与安慰剂组相比,布立哌唑组显示出比基线高大约5分的降低.Brexpiprazole通常具有良好的耐受性和安全性,当用于这种适应症时,常见的不良反应包括头晕,头痛,失眠,鼻咽炎,嗜睡,和尿路感染.像其他用于AD患者躁动的抗精神病药一样,与安慰剂相比,布立哌唑与更高的死亡率相关.在长期护理环境中,它的使用有几个注意事项。益处包括耐受性良好的口服药剂和显示对躁动的统计学显著影响的临床数据。然而,尚未在针对其他抗精神病药的正面交锋临床试验中研究过,如果躁动评分降低转化为临床上有意义的差异,则有不同的意见。批准的布立哌唑信号有利的即将到来的药物为这一适应症,包括艾司西酞普兰和右美沙芬-安非他酮。艾司西酞普兰和右美沙芬-安非他酮目前都在进行临床试验。
Alzheimer\'s disease (AD) is a prevalent neurodegenerative disease characterized by progressive cognitive and functional decline. Nearly all patients with AD develop neuropsychiatric symptoms (NPSs). Agitation is one of the most distressing and challenging NPS.
Brexpiprazole is an oral antipsychotic and is the first approved pharmacologic agent in the United States for the treatment of agitation associated with dementia due to AD. Its effect is thought to be from its partial serotonin 5-HT1A and dopamine D2 receptor agonist activity and serotonin 5-HT2A receptor antagonism.
Brexpiprazole is a maintenance medication, and it should not be used \"as needed\" or as a \"PRN\" treatment for breakthrough agitation.
Brexpiprazole is a major substrate of CYP2D6 and CYP3A4. Dose adjustments may be required for drug interactions or impaired renal or hepatic function. Clinical trials found
brexpiprazole 2 to 3 mg/d demonstrated significant improvements in agitation, with brexpiprazole showing an approximate 5-point greater reduction on change in the Cohen-Mansfield Agitation Inventory total score at week 12 from baseline compared with placebo. Brexpiprazole is generally well tolerated and safe, and common adverse reactions when used for this indication include dizziness, headaches, insomnia, nasopharyngitis, somnolence, and urinary tract infections. Like other antipsychotics used for agitation in AD,
brexpiprazole is associated with higher mortality rates compared with placebo. In a long-term care setting, there are several considerations for its use. Benefits include an oral agent that is well tolerated and clinical data showing statistically significant effects on agitation. However, brexpiprazole has not been studied in head-to-head clinical trials against other antipsychotics, and there are differing opinions if the agitation score reductions translate to a clinically meaningful difference. The approval of brexpiprazole signals favorably for upcoming agents for this indication, including escitalopram and dextromethorphan-bupropion. Both escitalopram and dextromethorphan-bupropion are currently undergoing clinical trials.