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Introduction: 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., Areas Covered: The authors review the pharmacology, mechanism of action, pharmacokinetics, efficacy, safety and tolerability data of AVP-786, for the treatment of agitation in AD., Expert Opinion: 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.