Current and Emerging Pharmacological Approaches to Agitation in Alzheimer's Disease: A Narrative Review of New and Repurposed Therapies

Abstract

This narrative review explores current pharmacological treatments for agitation in Alzheimer's disease (AD). Agitation, a common and difficult-to-manage symptom in AD, often requires targeted intervention. While nonpharmacological methods, such as behavioral therapy and environmental modifications, are considered first line, they may not always be effective. In cases where these approaches fail, pharmacological treatment can become a necessary component of care. Historically, antipsychotics have been the mainstay of pharmacological treatment for agitation in AD; however, safety and efficacy concerns have prompted exploration into alternative treatments. The purpose of this narrative review is to synthesize current literature on pharmacological treatments for agitation in AD with a focus on new and repurposed drugs. It also examines agents that have failed to demonstrate clinical benefit, offering insights into the ongoing challenges of drug development in this area. This review synthesizes recent findings on various drug classes, including anticonvulsants, antipsychotics, selective serotonin reuptake inhibitors (SSRIs), atypical antidepressants, sedatives, anti-dementia drugs, dextromethorphan, and cannabinoids. Both brexpiprazole and risperidone have demonstrated efficacy and received approval from government agencies, including brexpiprazole in the USA and risperidone in parts of Europe. Despite these advances, concerns remain regarding their long-term use and safety profiles. As a result, multiple other therapies are currently being studied as possible alternative solutions. However, no other pharmacological agents are currently approved, underscoring the need for further research on safe and effective options for this vulnerable population.