Agitation in Alzheimer’s disease: From assessment to therapeutics

Abstract

Agitation is a neuropsychiatric syndrome characterized by excessive motor and/or verbal behaviors, with or without aggressive behaviors. The prevalence of agitation in Alzheimer’s disease varies from 5% to over 50%. Multiple factors have been implicated in its pathophysiology, including disease stage, comorbidity with other symptoms (e.g., psychosis, anxiety/depression), and psychosocial factors. Ruling out delirium and identifying environmental triggers are fundamental steps in the management of agitation in Alzheimer’s disease. For establishing an effective therapeutic plan, it is important to define duration, severity, and potential for harm. While non-pharmacological approaches are considered the first line of intervention, pharmacological agents are frequently used in the treatment of agitation. Antipsychotics are commonly used in acute agitation. For chronic agitation, serotonin-selective reuptake inhibitors, especially citalopram and escitalopram, are often preferred due to safety concerns associated with the long-term use of antipsychotics. Promising novel strategies, such as new compounds and neuromodulation, are likely to be incorporated into agitation therapeutics in the next few years.

Keywords: Alzheimer’s disease; Dementia; Agitation; Aggression; Antipsychotics; Antidepressants

Core Tip: In Alzheimer’s disease, agitation is a clinically relevant neuropsychiatric syndrome managed by non-pharmacological and pharmacological approaches. Ruling out delirium, identifying and addressing environmental triggers (e.g., change in caregiver) are fundamental therapeutic steps. Antipsychotics (e.g., brexpiprazole, risperidone) are commonly used in acute agitation, especially in the context of potential harm to self and others. For chronic agitation, serotonin-selective reuptake inhibitors (e.g., escitalopram) are preferred.