Pharmacotherapeutic landscape for the management of agitation associated with Alzheimer's disease.

INTRODUCTION

Agitation associated with Alzheimer's disease (AAD) is common, persistent, and strongly linked to caregiver burden, emergency care, and institutionalization. Pharmacologic options have historically been limited by modest efficacy and safety liabilities in the geriatric population, creating a major treatment gap.

AREAS COVERED: This narrative review summarizes established and emerging pharmacotherapies for AAD, emphasizing comparative efficacy, geriatric-relevant safety, and real-world feasibility. A literature search was conducted in PubMed/MEDLINE and ClinicalTrials.gov from database inception through 31 January 2026, prioritizing the most recent decade when applicable, and complemented these searches with hand searches of key trials, meta-analyses, guidelines, and publicly available regulatory or sponsor communications for late-stage programs. Evidence is synthesized qualitatively due to heterogeneity in definitions and outcomes. We discuss antipsychotics, serotonergic agents, drugs with negative trials, and pipeline approaches such as dextromethorphan-based combinations and adrenergic strategies.

EXPERT OPINION: The field is shifting from broad off-label prescribing toward phenotype-informed, trial-validated treatments. Brexpiprazole establishes regulatory feasibility, while dextromethorphan-based combinations, particularly AXS-05, appear promising, including signals for durability. Progress will depend on harmonized outcomes, longer-term safety data, and pragmatic trials that prioritize function, caregiver impact, and crisis prevention.