Department of Psychiatry and Clinical Psychology, Saint Georges Hospital University Medical Center University of Balamand, Beirut, Lebanon.
Department of Psychiatry and Behavioral Neuroscience, Saint Louis University School of Medicine, Missouri, USA.
Expert Opin Pharmacother. 2021 May;22(7):783-795. doi: 10.1080/14656566.2021.1882995. Epub 2021 Feb 26.
To date, there is no FDA-approved treatment for agitation in Alzheimer's disease (AD). Medications currently used off-label have modest clinical efficacy and serious side effects.
The authors review the pharmacology, mechanism of action, pharmacokinetics, efficacy, safety and tolerability data of AVP-786, for the treatment of agitation in AD.
AVP-786, the deuterated form of dextromethorphan/quinidine (AVP-923) which is an approved treatment for Pseudo-Bulbar Affect, emerges as a promising and safe treatment for agitation in AD. Deuteration is an innovative technology that accelerates drug development by conducting faster and less costly clinical trials. No phase II trial was conducted with AVP-786 for the treatment of agitation in AD; the decision to expedite the development of this drug was based on a successful phase II study with AVP-923. Phase III trials with AVP-786 (TRIAD-1 and TRIAD-2) showed mixed findings probably due to the difference in study design. Future phase III studies should use innovative study designs such as the Sequential Parallel Comparison Design to mitigate high placebo response, and the Cohen-Mansfield Agitation Inventory for agitation assessment. They should also include positron emission tomography studies to assess occupancy of various receptors in the brain after AVP-786 is administered.
迄今为止，FDA 尚未批准用于治疗阿尔茨海默病（AD）患者激越症状的药物。目前临床上常使用一些未被批准用于该适应证的药物，但这些药物的疗效有限，且具有严重的副作用。
本文作者综述了 AVP-786 的药理学、作用机制、药代动力学、疗效、安全性和耐受性数据，该药用于治疗 AD 患者的激越症状。
AVP-786 是右美沙芬/奎尼丁（AVP-923）的氘代形式，后者是假性延髓情绪波动的一种已获批治疗药物，作为 AD 患者激越症状的一种有前景且安全的治疗药物而出现。氘代是一种创新技术，通过进行更快、成本更低的临床试验来加速药物开发。目前尚未开展 AVP-786 治疗 AD 患者激越症状的 II 期临床试验；加速开发该药的决定是基于 AVP-923 的 II 期成功研究。AVP-786 的 III 期临床试验（TRIAD-1 和 TRIAD-2）结果喜忧参半，这可能是由于研究设计的差异所致。未来的 III 期研究应采用创新的研究设计，如序贯平行比较设计，以减轻安慰剂的高应答率，并采用 Cohen-Mansfield 激越量表评估激越症状。此外，这些研究还应包括正电子发射断层扫描研究，以评估给药后大脑中各种受体的占有率。
