A 2023 update on the advancements in the treatment of agitation in Alzheimer's disease

• Published in: Expert opinion on pharmacotherapy Vol. 24; no. 6; p. 691
• Main Authors: Lee, Daniel, Clark, Emily D, Antonsdottir, Inga M, Porsteinsson, Anton P
• Format: Journal Article
• Language: English
• Published: England 13.04.2023
• Subjects: Acetylcholinesterase - therapeutic use; Alzheimer Disease - complications; Alzheimer Disease - drug therapy; Alzheimer Disease - psychology; Antidepressive Agents - therapeutic use; Antipsychotic Agents - therapeutic use; Humans; Psychomotor Agitation - drug therapy; Psychomotor Agitation - etiology; Treatment Outcome; Prazosin; Agitation; Cannabinoids; Alzheimer’s disease; Escitalopram; Neuropsychiatric symptoms; Dexmedetomidine; Brexpiprazole; Dextromethorphan; Masupirdine
• ISSN: 1744-7666
• DOI: 10.1080/14656566.2023.2195539

Neuropsychiatric symptoms (NPS) in Alzheimer's Disease (AD) are associated with negative outcomes for patients and their care partners. Agitation is a common and distressing NPS, without safe and effective treatments. Nonpharmacological interventions are first line treatment, but not effective or appropriate for every patient. Current pharmacological treatments of agitation in AD include off-label use of antipsychotics, sedative/hypnotics, anxiolytics, mood-stabilizing anticonvulsants, acetylcholinesterase inhibitors, NMDA receptor antagonists, and antidepressants. Despite prevalent use, efficacy and safety concerns remain. Better understanding of neurobiological mechanisms of agitation have fueled recent clinical trials. This article is an update to our 2017 review. Comprehensive search of ClinicalTrials.gov was completed from January 2017 to February 2023 using the search terms "Alzheimer's Disease" and "Agitation". Subsequent scoping review was completed in PubMed and Google Scholar. Several agents were identified, including: brexpiprazole, cannabinoids, dexmedetomidine, dextromethorphan, escitalopram, masupirdine, and prazosin. Clinical trials utilize both novel and repurposed agents for agitation in AD. With increasing understanding of the neurobiological mechanisms that fuel development of agitation in AD, use of enahanced trial design and conduct, advanced statistical approaches, and accelerated pathways for regulatory approval, we advance closer to safe and efficacious treatment options for agitation in AD.