Targeted Treatment of Agitation in Alzheimer's Dementia: Prioritizing Function and Safety Over Sedation and Other...

Agitation is a common and clinically significant neuropsychiatric condition in Alzheimer's dementia. Clinicians across the spectrum of care settings frequently encounter agitation but often lack practical clinical guidance. In April 2026, a consensus panel of clinical experts reviewed the literature and developed guidance for managing agitation in Alzheimer's dementia. The panel emphasized the critical role of primary care in agitation management and discussed different treatment approaches for optimizing patient and caregiver outcomes. Treatment should prioritize reduction of patient and caregiver distress and preservation of function rather than mere sedation. Discussion of neurobiology focused on the evolving models of frontal-limbic imbalance as the key driver of agitation in progressing Alzheimer's disease and implications for pharmacologic selection. The panel reviewed evidence on safety and efficacy of pharmacologic agents commonly used in agitation management and concluded that efficacy and safety profiles should guide clinical decision-making. The panel recommended conducting a behavioral assessment using validated tools, ruling out reversible causes, and using nonpharmacologic interventions as the first-line approach prior to starting pharmacologic treatment. Finally, setting-specific considerations were discussed. These recommendations complement prior guidance with a primary-care clinical decision pathway that matches treatment to the neurobiology of agitation and to comparative safety profiles, and that extends to the assessment, documentation, and coding clinicians need at the point of care. The goal is to help clinicians select evidence-based interventions for agitation in Alzheimer's dementia that prioritize safety, alertness, functional engagement, and caregiver well-being while minimizing the serious harms that have historically accompanied off-label management in this population, including excess mortality, cerebrovascular events, cognitive impairment, falls, and sedation.

Prim Care Companion CNS Disord 2026;28(5):haadachi2603.